Effect of smoking on the long-term course of ulcerative colitis

OBJECTIVE: To evaluate the effects of smoking on the long term clinical course in patients with ulcerative colitis. METHODS: The medical charts of 556 patients with ulcerative colitis were reviewed retrospectively. Patients were classified as smokers (n = 85) or nonsmokers (n = 471) according to their smoking status during the course of the disease. Extent of colonic lesions, complications, medical requirements, and actuarial rate of colectomy were compared in smokers and nonsmokers. RESULTS: Mean follow-up (+/- SD) was longer in smokers than in nonsmokers (116 +/- 107 mo, vs 87 +/- 94 mo.). Less smokers than nonsmokers required oral steroids (52 vs 63%, P = 0.05). No difference between the groups was observed regarding the use of salicylates, the need for intravenous steroids, for immunosuppressive drugs, for colectomy, and the occurrence of complications. The actuarial rate of colectomy was less in smokers than in nonsmokers (32 +/- 12% and 42 +/- 6% at 10 years respectively. P = 0.04). Initial and cumulative extent of the disease process did not differ between the groups. However, in the subgroup of patients with limited disease at onset, development of pancolitis was less frequent in smokers than in nonsmokers (14 and 26%, respectively, P = 0.04). CONCLUSION: The lesser need for oral steroids and the lower actuarial rate of colectomy in smokers suggest that ulcerative colitis in smokers is characterized by a less severe clinical presentation and a better long term prognosis than in nonsmokers.     

Correlation of a common mutation in the methylenetetrahydrofolate reductase gene with plasma homocysteine in patients with premature coronary artery disease

BACKGROUND: Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low-dose oral methotrexate in patients with inflammatory bowel disease. METHODS: Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels. RESULTS: Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25-0.87 micro M. The mean Cmax values were similar in all patient groups (0.59 +/- 0.12, 0.69 +/- 0.16 and 0.54 +/- 0.18 micro M, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0-120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P < 0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r = -0.74) only in Crohn's disease patients but not in the other patient groups. CONCLUSIONS: Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally.     

Crypt hyperplasia related to increased lymphocyte activation in the rectal mucosa of children with ulcerative colitis

The presence of cells positive for interleukin-2 receptors (CD25) and the proportion of Ki-67 positive dividing cells in the crypts were studied with monoclonal antibodies using sensitive immunohistochemical techniques in the rectal biopsy specimens taken from 13 children with inflammatory bowel disease (4 Crohn's disease and 9 ulcerative colitis) and 10 controls. In all specimens, but one, from patients CD25+ cells were found in the surface and crypt epithelium, while in none of controls were seen such cells. The mean percentage of dividing crypt cells was significantly higher in ulcerative colitis (36.0%) and in Crohn's disease (34.6%) than in controls (18.4) (p < 0.001 in both comparisons). In ulcerative colitis, a correlation between CD25/CD3 ratios in the surface and crypt epithelium and the percentage of dividing crypt cells was found. We conclude that activated lymphocytes have a role in the crypt hyperplasia of ulcerative colitis.     

Suppression of male-specific cytochrome P450 isoforms by bisphenol A in rat liver

IBD results from the interaction of genetic and environmental factors (e.g., smoking). Clinical suspicion is the key to diagnosis, which then rests on colonoscopy, histopathological examination of multiple biopsy specimens, small bowel barium radiology and faecal examination. The primary goal of treatment is remission--histological in ulcerative colitis and symptomatic in Crohn's disease. Treating active disease and maintaining remission require different approaches. For active disease, short term corticosteroids are the mainstay of treatment, while immunosuppressive drugs are important in chronically active disease. For maintenance, mesalazine-delivering drugs and immunosuppressive agents are efficacious in both ulcerative colitis and Crohn's disease; patients with Crohn's disease should not smoke.     

Pharmacokinetics of nicotine carbomer enemas: a new treatment modality for ulcerative colitis

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis.     

Incidence of inflammatory bowel diseases in the department of Puy-de-D?me in 1993 and 1994. EPIMICI. Epidémiologie des Maladies Inflammatoires Cryptogenetiques de l'Intestin group

The aim of this prospective epidemiological study was to investigate the incidence of Inflammatory Bowel Disease in the Puy-de-D?me county using the same methodology as EPIMAD's registry. METHODS: From 01/01/93 to 31/12/94, each gastroenterologist (n = 22) collected patients consulting for the first time with clinical symptoms compatible with inflammatory bowel disease. Data were reported on a questionnaire by an interviewer practitioner. The final diagnosis of Crohn's disease and ulcerative colitis was made in a blind manner by two expert gastroenterologists and recorded according to the Calkin's criteria as definite, probable, or possible diagnosis, or unclassifiable chronic colitis or acute colitis. RESULTS: 167 new cases were identified: 112 (67.1%) inflammatory bowel disease for the combined group of definite and probable cases with 79 Crohn's disease (70.5%), 29 ulcerative colitis (25.9%) of which 11 ulcerative proctitis (37.9%), 4 unclassifiable chronic colitis (3.6%) and 55 acute colitis (32.9%). The crude and age-adjusted incidence (per 10(5)/year) was respectively 6.6 and 5.7 for Crohn's disease and 2.4 and 1.9 for ulcerative colitis. The highest age-specific incidence rate for Crohn's disease was between 40-49 years (14.1) and for ulcerative colitis between 80-89 years (6.8). The female/male ratio was 0.8 for Crohn's disease and 1.1 for ulcerative colitis. The median age at the time of diagnosis was 42.6 years for Crohn's disease and 35.3 years for ulcerative colitis. CONCLUSIONS: These preliminary findings revealed a high incidence of Crohn's disease and low of ulcerative colitis in this county. However, these results must be managed carefully because these data were recorded only on two years and the inflammatory bowel disease classified possible and acute colitis require a follow-up.     

25-hydroxy vitamin D deficiency with reduction of intestinal calcium absorption and bone density in chronic alcoholism

Plasma levels of 25-hydroxycalciferol (25-OH-D), 47-calcium intestinal absorption, bone mineral content and the biologic parameters of phospho-calcium metabolism were studied in 30 chronic alcoholics, 15 with Laennec's cirrhosis (group A) and 15 without (group B). These patients were compared with 27 normal subjects. In group A, the mean 25-OH-D plasma level was 23.7 +/- SD 18.5 microgram/l and in group B 35.2 +/- SD 21.8 microgram/l. These mean levels were lower than those of the control group, which were 57.2 +/- SD 22.5 microgram/l (p less than 0.001). The mean value of the 47Ca intestinal absorption, measured as the percentage of the ingested dose per litre of plasma and multiplied by the body weight, was also significantly lower in group A, which was 140 +/- SD 47 (p less than 0.01), and in group B, which was 145 +/- SD 69 (p less than 0.05), compared with the normal subjects whose average was 182 +/- SD 45.6. Similarly, the total plasma calcium was low: 1.99 +/- SD 0.24 mmol/l in all the alcoholics, while that of the control group was 2.22 +/- SD 0.18 mmol/l (p less than 0.001). For the 30 chronic alcoholics there was a positive correlation between 25-OH-D and 47Ca intestinal absorption, (r = 0.484; p less than 0.004). This suggests that in chronic alcoholism the deficiency of 25-OH-D induces a diminution of the intestinal absorption of calcium which, in the long term, can result in bone demineralization evidenced in the patients studied by a bone mineral content lower than normal (p less than 0.001).     

The analgesic effect of fentanyl, morphine, meperidine, and lidocaine in the peripheral veins: a comparative study

It has been reported that in patients with inflammatory bowel disease (IBD), the airways are involved, and a number of clinical manifestations have been described. The aim of this study was to investigate the function of the small airways in IBD. Thirty patients with IBD (mean age, 47 yr), 12 with Crohn's disease and 18 with ulcerative colitis, were studied and compared with a control group of 16 normal subjects. Maximal expiratory flow-volume curves were performed breathing room air and a mixture of 80% helium, 20% oxygen. The differences of flows at 50% of FVC (delta Vmax50) and the volume of equal flows (Visov) were calculated as indices of small airways function. In addition, spirometry, lung volumes, and diffusing capacity were measured. Visov was statistically significantly greater in patients with either CD or UC than in control subjects (x +/- SD) (24.99 +/- 1.35 and 25.95 +/- 1.5 versus 20.1 +/- 1.39), (p < 0.01 and p < 0.001, respectively). A reduction in TL(CO) was noticed in the active stage of the disease in both groups of patients (p < 0.05). This may indicate that lung parenchyma is also involved in active IBD. Our results suggest that the function of the small airways and diffusion capacity of the lungs are affected in patients with IBD.     

Incidence of inflammatory bowel disease in northern France (1988-1990)

There were no data concerning the incidence of inflammatory bowel disease (IBD) in France. The aim of this study was to investigate the incidence of Crohn's disease and ulcerative colitis in northern France. This prospective population based study was realised through the gastroenterologists of the region Nord-Pas de Calais and the Somme Department. Each gastroenterologist referred patients consulting for the first time with clinical symptoms compatible with IBD. Data were collected by an interviewer practitioner present at the gastroenterologist's consulting room. Two independent expert gastroenterologists assessed each case in a blind manner and made a final diagnosis of Crohn's disease, ulcerative colitis, ulcerative proctitis, or unclassifiable chronic colitis. From 1988 to 1990, 1291 cases of IBD were recorded: 674 (52%) Crohn's disease, 466 (36%) ulcerative colitis including 162 proctitis (35%), and 151 (12%) unclassifiable chronic colitis. The mean annual incidence was 4.9 per 100,000 for Crohn's disease and 3.2 for ulcerative colitis. The sex ratio F/M was 1.3 for Crohn's disease and 0.8 for ulcerative colitis. The highest age specific incidence rate for Crohn's disease was between 20 and 29 years: 13.1 for women and 9.8 for men. The highest age specific incidence rate for ulcerative colitis was between 20 and 39 years: 5.5 for women and 6.5 for men. This first French prospective study has shown an incidence rate for Crohn's disease comparable with that seen in north European studies but lower than that seen for ulcerative colitis. These results could be related to the different environmental factors or the genetic background of the population studied, or both.     

Risk indicators for inflammatory bowel disease

We investigated the association between different risk indicators and inflammatory bowel disease in a case-control study based on the population of Stockholm County during 1980-1984. Information on physical activity, oral contraceptives, some previous diseases and childhood characteristics was collected using a postal questionnaire for 152 cases of Crohn's disease, 145 cases of ulcerative colitis, and 305 controls. The relative risk (RR) of Crohn's disease was inversely related to regular physical activity and estimated at 0.6 (95% CI: 0.4-0.9) and 0.5 (95% CI: 0.3-0.9) for weekly and daily exercise, respectively. Having psoriasis prior to the inflammatory bowel disease was associated with an increased relative risk of Crohn's disease (RR = 2.9, 95% CI: 1.1-7.9). Use of oral contraceptives was associated with an increased RR of 1.7 for both Crohn's disease and ulcerative colitis. Crohn's disease confined to the colon and total ulcerative colitis at diagnosis were most strongly associated with oral contraceptives.     

Antineutrophil cytoplasmic antibodies in Estonian patients with inflammatory bowel disease. Prevalence and diagnostic role

BACKGROUND/AIMS: In Estonia, the incidence of ulcerative colitis and especially Crohn's disease appears to be rare. Antineutrophil cytoplasmic antibodies (ANCA) are frequently found in ulcerative colitis but less frequently in Crohn's disease, their pathophysiological significance is still unclear. METHODOLOGY: Fifty-nine serum samples from patients with ulcerative colitis, 17 with Crohn's disease, 25 with irritable bowel syndrome, and 86 healthy persons were studied. Sera were analyzed for the presence of ANCA by indirect immunofluorescence, and enzyme-linked immunosorbent assay for specific ANCA using different antigens was performed. RESULTS: ANCA were detected in 29 of 59 (49%) patients with ulcerative colitis, 4 of 17 (24%) patients with Crohn's disease, and in 4 of 111 (4%) controls. The immunofluorescence staining was mostly perinuclear (pANCA). There was no correlation between ANCA and the duration or extent of the inflammatory bowel disease. In specific enzyme-linked immunosorbent assays, only 14 sera elicited binding above the normal range. CONCLUSIONS: Although the prevalence of ulcerative colitis and Crohn's disease in Estonia is much lower than in European countries, there seem to be no differences in the presence of ANCA.     

Prevalence of enteropathogenic bacteria in surgically treated chronic inflammatory bowel disease

BACKGROUND/AIMS: In order to assess the potential impact of bacterial eradication on recurrence rates, the prevalence of various enteropathogenic bacteria and toxins in chronic inflammatory bowel diseases (CIBD) was prospectively examined. METHODOLOGY: Stool, sera and gut tissue samples from a total of 59 patients (33 males, 26 females; mean age: 42 years +/- 14; 21 Crohn's disease, 14 ulcerative colitis, 24 controls) were examined for the presence of enteropathogenic bacteria by culture, immunoblotting and PCR. RESULTS: Conventional cultures failed to detect obligate pathogenic bacteria. By PCR, mycobacteria were found in 85% of all groups, with mycobacterium paratuberculosis not detected. Yersinia species were observed in 63% of patients with Crohn's disease, in 46% of patients with ulcerative colitis, and in 36% of the control patients. Pathogenic E. coli were identified in stool samples of three patients with ulcerative colitis (21%) by amplifying the EAE-gene, one of whom exhibited shiga-like-toxin as well. CONCLUSIONS: We concluded that mycobacteria do not play a causative role in CIBD. Yersinia species seem to persist in intestinal tissue in CIBD patients without adequate immune response and might, thus, contribute to tissue destruction. E. coli infections contribute to the disease process in a small group of patients with ulcerative colitis and their eradication might eliminate the need for immediate surgical intervention.     

Influence of the smoking habit in the surgery of inflammatory bowel disease

The smoking habit is a key factor in the development of inflammatory bowel disease (IBD), but little information exists as to the relationship between smoking habit, the need of surgery and its complications. OBJECTIVES: To investigate the relationship between smoking habit, the need of surgery, their complications and clinical recurrence after surgery in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We studied a group of 62 patients (22 with UC and 40 with CD) with previous surgery. We analyzed the clinical and surgical characteristics of the disease. Smoking habit was established by a personal interview. This group of patients was compared with another control group of 202 patients (133 with UC and 69 with CD) with IBD without previous surgery. RESULTS: Smoking habit was similar between operated and non-operated patients for both UC (73% and 80% non-smokers) and CD (67% and 63% smokers) The number and type of complications after surgery were not related with smoking habit. In CD patients, although the recurrences did not depend on the smoking habit, they did occur earlier in smokers than in non smokers (83.6 +/- 21 vs 155 +/- 50 weeks, p = ns). CONCLUSIONS: The smoking habit does not seem to influence significantly the need of surgery and post surgical development of IBD, although in CD the smokers seems to present recurrence before non smokers.     

The role of neutrophils in the pathogenesis of idiopathic pulmonary fibrosis

STUDY OBJECTIVES: The prognostic value of the neutrophil count in BAL fluid (BALF) has been controversial. The role of neutrophils in this inflammatory lung disease, therefore, was evaluated in this study by additional measures. MATERIALS AND METHODS: We performed BAL in 22 patients with idiopathic pulmonary fibrosis (IPF) diagnosed by open lung biopsy specimen. Percent polymorphonuclear leukocyte (PMN) in BALF and absolute neutrophil counts were compared with those of normal nonsmokers. Elastase complexed to alpha-1-proteinase inhibitor (alpha1-PI) in plasma and BALF was measured as a marker of elastase burden, and neutrophil distribution in 22 lung tissues was observed by immunohistochemistry using antineutrophil elastase antibody. RESULTS: Percent PMN and absolute neutrophil counts in BALF did not increase in patients with IPF as compared with normal nonsmokers (n=15); the plasma elastase-alpha1-PI complex value (mean+/-SE) of patients with IPF (668.5+/-112.4 ng/mL) was significantly high as compared with that of normal nonsmokers (130.3+/-21.3, p<0.001). In addition, the BALF elastase-alpha1-PI complex value (mean+/-SE) of patients with IPF was also significantly high (333.1+/-87.0 ng/mg albumin) as compared with that of normal nonsmokers (83.1+/-29.3 ng/mg albumin, p<0.05). Immunohistochemistry demonstrated considerable numbers of neutrophils infiltrating the lung parenchyma in biopsy specimens obtained by open lung biopsy. CONCLUSIONS: These results suggested that although the neutrophil count in BALF could not represent the distribution of neutrophil in the lung, high levels of neutrophil elastase were demonstrated in lung parenchyma and also in both BALF and sera. Therefore, neutrophils might indeed play an important role in the pathogenesis of IPF.     

Treatment of refractory rapid cycling bipolar disorder with risperidone

BACKGROUND: There is evidence for a hypercoagulable state in inflammatory bowel disease (IBD), and small vessel thrombosis has been identified in the bowel of patients with Crohn's disease, suggesting thrombosis as a possible etiologic factor. Activated protein C (APC) resistance is the most common inherited disorder leading to thrombosis and accounts for 30% to 40% of episodes of idiopathic venous thrombosis. METHODS: The prevalence of APC resistance was studied in 23 patients with IBD (17 with Crohn's disease, 6 with ulcerative colitis) and in 11 control subjects with recurrent abdominal pain or celiac disease, using an APC resistance screening method. RESULTS: One patient with Crohn's disease had a positive screen result, two patients (one with Crohn's, one with ulcerative colitis) had borderline results, and results in all of the control subjects were normal. One patient with Crohn's disease had a history of a thromboembolic event but had a normal screen result. CONCLUSIONS: Activated protein C resistance does not seem to play a major role in the etiology of the hypercoagulable state in inflammatory bowel disease.     

Prothrombin fragment 1 + 2 and thrombin-antithrombin III complex as markers of activation of blood coagulation in inflammatory bowel diseases

OBJECTIVES AND METHODS: The aims of the present work were to assess the presence of thrombin generation in Crohn's disease and in ulcerative colitis by using the prothrombin fragment 1 + 2 and the thrombin-antithrombin III complex assays and to study the possible relationships between these markers and disease activity. RESULTS: Prothrombin fragment 1 + 2 and thrombin-antithrombin III complex were significantly raised in patients with Crohn's disease (n = 69) and with ulcerative colitis (n = 25) as compared with healthy controls (n = 50). In Crohn's disease these two markers of thrombin generation were correlated with the Van Hees index (P < 0.05 and P < 0.001, respectively); values were significantly different from controls even in the patient group displaying the lowest disease activity (P < 0.001). No correlation was found with tumour necrosis factor alpha and C-reactive protein; nevertheless patients with C-reactive protein less than or equal to 10 mg/l had significant lower values of prothrombin fragment 1 + 2 (P < 0.03). In ulcerative colitis prothrombin fragment 1 + 2 and thrombin-antithrombin III complex were significantly increased by comparison with controls, were higher in patients with pancolitis and correlated with C-reactive protein (P < 0.002 and P < 0.009, respectively). CONCLUSION: These data show that prothrombin fragment 1 + 2 and thrombin-antithrombin III complex are increased in inflammatory bowel diseases and suggest that thrombin generation might be an early event in their pathogenesis.     

Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease with special attention for IgA-class antibodies

Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) of the IgG class have been reported in inflammatory bowel disease, mainly in ulcerative colitis. Since this disease affects the gastrointestinal tract, we determined whether IgA class ANCA were present in inflammatory bowel disease. We used an indirect immunofluorescence assay for IgG and IgA ANCA testing. Sera from 34 patients with Crohn's disease and 29 patients with ulcerative colitis were collected together with clinical and laboratory data. We found IgA class ANCA of a perinuclear type in 52% of patients with ulcerative colitis and in 9% of Crohn's disease patients. There was a significant association between the presence of IgA ANCA and the occurrence of blood in the feces in the ulcerative colitis group (P = 0.03). IgG ANCA was found in 56% of patients with ulcerative colitis and in 7% of patients with Crohn's disease. Because of partial overlap between IgG and IgA ANCA positivity, the sensitivity of ANCA testing in ulcerative colitis increased from 56% up to 78% by combining IgG and IgA assays. In conclusion, IgA ANCA occurs with a high prevalence in ulcerative colitis. Moreover there is a possible relationship between IgA ANCA and disease activity in ulcerative colitis.     

Comparison of three different methods for radiolabelling human activated T lymphocytes

The purpose of this study was to determine both the selenium (Se) level and glutathione peroxidase (GSH-Px) activity in plasma, erythrocytes and platelets from 51 healthy Japanese individuals. The Se levels (mean +/- SD) of plasma, erythrocytes and platelets were 117.4 +/- 15.7 micrograms/L, 0.954 +/- 0.159 microgram/g hemoglobin, and 4.93 +/- 1.52 ng/mg protein, respectively, and GSH-Px activity was 318 +/- 50 U/L, 18.0 +/- 5.0 U/g hemoglobin, and 0.142 +/- 0.035 U/mg protein, respectively. There was a negative correlation between age and the platelet Se level in men (r = -0.761, p < 0.001), and a positive correlation between the plasma and platelet GSH-Px activities in women (r = 0.663, p < 0.001).     

Direct detection of Mycobacterium tuberculosis complex and M. avium complex in tissue specimens from cattle through identification of specific rRNA sequences

BACKGROUND: In many cases inflammatory bowel disease is accompanied by extraintestinal manifestations. This results in lowering of live quality. The aim of this study was to gather data retrospectively about initial symptoms, extraintestinal manifestations and course of pregnancy in a large unselected population with inflammatory bowel disease in South Germany. PATIENTS AND METHODS: Data from 1975 to 1989 (392 patients) were analyzed and partially compared with data from 1992 to 1995 (211 patients). RESULTS: Patients with Crohn's disease in average have been 25 years old at the time point of initial symptoms, whereas the age of ulcerative colitis patients was 30 years (p < 0.0001). The number of Crohn's disease patients with a long interval between initial symptoms and diagnosis (> 1 year) was significantly decreased in the second population (50% vs 38%; p < 0.05). Dominant initial symptoms in Crohn's disease were indisposition, abdominal pain and nonbloody diarrhea in contrast to ulcerative colitis which manifested mostly with bloody diarrhea. Extraintestinal manifestations occurred in 76% of patients with Crohn's disease and 64.6% with ulcerative colitis. Complications during the course of pregnancy have been detected in 40.5% in Crohn's disease and 60% in ulcerative colitis. CONCLUSION: A better knowledge of initial symptoms and extraintestinal manifestations in inflammatory bowel disease can help to decrease the interval between initial symptoms and the diagnosis. Pregnancy in patients with inflammatory bowel disease needs to be treated with special care.     

Interleukin-1 receptor antagonist in differential diagnosis of inflammatory bowel diseases

BACKGROUND: Immunoregulatory properties of cytokines may mediate disordered inflammatory events in inflammatory bowel diseases (IBDs). On the basis of data obtained in experimental colitis, the hypothesis has been advanced that in IBD the balance between interleukin-1 (IL-1) and the naturally occurring IL-1 receptor antagonist (IL-1ra) might influence disease expression. OBJECTIVE: We studied the profiles of IL-1ra and acute phase proteins produced by activated macrophages to determine whether the level of IL-1ra in peripheral blood is a marker of disease activity in IBD and a possible differential diagnostic marker. PATIENTS AND METHODS: Levels of IL-1ra, serum neopterin, urinary neopterin, alpha 1-glycoprotein and C-reactive protein (CRP) were measured in 80 patients with ulcerative colitis, Crohn's disease or infectious colitis. RESULTS: Levels of IL-1ra were markedly increased in patients with active ulcerative colitis or active Crohn's disease compared with those in patients with infectious colitis. Patients with active Crohn's disease had significantly higher serum IL-1ra levels than patients with active ulcerative colitis. Moreover, a positive correlation was found between levels of C-reactive protein, alpha 1-glycoprotein, and serum neopterin and the level of IL-1ra in active Crohn's disease but not in active ulcerative colitis, strongly suggesting that the pathogenesis of the two conditions differs. CONCLUSION: Levels of IL-1ra in the peripheral blood of patients with IBD are of clinical relevance, representing a potent marker of disease activity and a possible differential diagnostic marker.