Clinical status of ulcerative colitis in patients who smoke

OBJECTIVES: Ulcerative colitis (UC) is largely a disease of nonsmokers. There are few patients who are current smokers, but we have identified a group and reviewed their clinical status, disease activity, and nicotine exposure to examine whether they remain well controlled while smoking. METHODS: Fifty-one patients from three centers with verified UC were reviewed. RESULTS: Thirty of the group were men; mean age 50 yr, with a mean age of onset of 37 yr. Twenty-two patients had proctosigmoid disease, 12 involvement of left colon, and 17 total colitis. All were current smokers; 41 were cigarette smokers averaging 17 daily. At the onset of colitis 30 were nonsmokers, 25 of them were ex-smokers and 19 developed colitis within 2 yr of stopping smoking. Twenty-eight believed smoking improved disease activity and none felt smoking had a detrimental effect on their UC. Eleven were receiving no medication for UC, 40 were receiving 5-ASA (5-aminosalicylic acid) preparations, and only two took oral steroids. All were in clinical remission, with the exception of one patient; mean St. Marks score was 1.5, out of a possible total of 22. Sigmoidoscopic grades were inactive in all patients except three. Histological assessment showed significant activity in only five. Median serum nicotine was 8 ng/ml (range, 0.4-24.4), median serum cotinine 180 ng/ml (range, 20-453), with corresponding salivary cotinine of 255 ng/ml (range, 34-683). Median rise in nicotine 2 min after a cigarette in 35 patients was 12.1 ng/ml (range, 0.4-44). CONCLUSIONS: Because most current smokers with UC have inactive disease, smoking may contribute to the clinical remission in these patients.     

Pneumatic lithotripsy applied through deflected working channel of miniureteroscope: results in 143 patients

OBJECTIVE: Transdermal nicotine appears to be of benefit in the short-term treatment of patients with ulcerative colitis. The aim of this study was to determine its long-term effects. DESIGN: A randomized, comparative study. PATIENTS AND METHODS: Patients with mild to moderate clinical relapses of left-sided ulcerative colitis during maintenance treatment with mesalamine 1 g b.i.d. were allocated to an additional treatment with either transdermal nicotine or prednisone for 5 weeks. The first consecutive 15 patients per group, with clinical and endoscopic signs of remission, were followed up for 6 months, while continuing mesalamine maintenance treatment. RESULTS: Relapses of active colitis were observed in 20% of patients formerly treated with nicotine and in 60% of patients in the prednisone group (P = 0.027). Relapses occurred earlier in the latter group. CONCLUSION: Our results confirm that nicotine is useful in cases of ulcerative colitis with mild or moderate activity and suggest that remissions induced by nicotine may last longer than those obtained with oral corticosteroids.     

Intervention within days for some orbital floor fractures: the white-eyed blowout

OBJECTIVE: Exposures to respirable suspended particles (RSP) and environmental tobacco smoke (ETS) were assessed in Prague, Czech Republic, to determine the range and degree of personal exposure by means of personal monitoring over a 24-h period. DESIGN: Self-reported nonsmokers were randomly selected from a representative sample of the population of Prague. Housewives were recruited into one group, primarily for assessment exposures in the home, and office workers were recruited into a second group for assessment of the contribution from the workplace. METHODS: A total of 238 randomly selected nonsmoking subjects collected air samples near their breathing zone by wearing personal monitors for 24 h. Samples collected were analyzed for RSP, nicotine, 3-ethenylpyridine, and ETS particles (using ultraviolet absorbance, fluorescence, and solanesol measurements). Saliva cotinine analyses were also undertaken to confirm the nonsmoking status of the subjects. RESULTS: The most highly exposed subjects in this study were office workers both living and working with smokers. Median time-weighted average exposure concentrations of 60 microg m(-3)RSP, 16 microg m(-3)ETS particles, and 1.6 microg m(-3) nicotine were determined for these subjects, who also had the highest median saliva cotinine level of 2.4 ng ml(-1). Housewives living in nonsmoking households were the least exposed subjects in this study, showing levels of 32 microg m(-3) RSP, 0.17 microg m(-3) ETS particles, and 0.15 microg m(-3) nicotine. As based upon median levels of ETS particles and nicotine, no group would potentially inhale or be exposed to more than 10 cigarette equivalents per year (CE/y) and the least exposed would inhale less than 1 CE/y. The most highly exposed (90th percentile levels) nonsmokers in this study, who both worked and lived with smokers, would potentially inhale up to 29 CE/y. Overall, the workplace was estimated to contribute between 45% and 49% of the annual exposure to nicotine and ETS particles, respectively. On the basis of determined saliva cotinine concentrations, a misclassification rate of between 1.7% and 2.5% was calculated. CONCLUSION: Highest exposures were apparent for office workers both working and living in smoking environments. and our findings suggest a significant contribution to overall ETS particle and nicotine levels from the workplace where smoking takes place. Overall, the rates at which subjects were determined to have misclassified their smoking status in this study were the lowest observed in any of the European cities investigated to date. Clearly, a more sensitive method of analysis for cotinine in body fluids is needed for more accurate determination of the levels expected for nonsmokers.     

Analysis of nicotine and cotinine in the hair of hospitality workers exposed to environmental tobacco smoke

The purpose of this study was to determine if hair nicotine and cotinine levels reflect relative exposure to environmental tobacco smoke (ETS) in subjects who worked in the hospitality industry, where public smoking was permitted. Hair samples from 26 subjects were analyzed by gas chromatograph/mass spectrometry techniques for nicotine and cotinine. An exposure gradient was shown for nicotine but not cotinine. Among nonsmokers, those working in bars where there are no public smoking restrictions had the highest hair nicotine levels, which were close to levels found in smokers. Nicotine measured in hair is useful as a biological marker for exposure to ETS from multiple sources. Bar workers in particular are exposed to high levels of ETS, which may adversely affect the health of nonsmokers.     

Text analysis of critical areas narrated by adolescents at an advisory service

AIM: To compare beclomethasone dipropionate 3 mg/60 mL enema (BDP) and prednisolone sodium phosphate 30 mg/60 mL enema (PP) once daily in patients with active distal ulcerative colitis. METHODS: One hundred and fifty-seven patients were enrolled in a multicentre, 4-week, randomized, double-blind trial. Patients were assessed at baseline, 2 and 4 weeks. RESULTS: Both treatment groups showed statistically significant improvement of clinical activity after 2 and 4 weeks. Endoscopy and biopsy showed a reduction in the activity score at the end of the treatment period in both groups. No statistically significant difference was observed between the two treatment groups. After 4 weeks, 29% of patients in the BDP group and 25% in the PP group were considered to be in clinical remission; an improvement was observed in 40% of patients on BDP and in 47% on PP. Mean morning plasma cortisol levels showed a slight but significant reduction in the PP group, while the ACTH test showed that neither drug interfered with the hypothalamic-pituitary-adrenal (HPA) axis function. No significant changes were observed in the laboratory tests. Finally, there was a low incidence of adverse events in both groups. CONCLUSIONS: It is concluded that, in the topical treatment of active distal ulcerative colitis, BDP 3 mg enemas are as efficacious as PP 30 mg enemas, without interference with the HPA axis.     

Gastrointestinal pH profiles in patients with inflammatory bowel disease

BACKGROUND: 5-Amino salicylic acid preparations are used in therapy for patients with inflammatory bowel diseases. The bioavailability of these drugs depends on their coating. AIM: To determine whether intraluminal pH is decreased by the presence of inflammation, thereby altering the release of 5-amino salicylic acid in the intestinal lumen. METHODS: Intraluminal gastrointestinal pH was measured by means of a radiotelemetry capsule in 12 healthy controls, in 12 patients with Crohn's disease (five with active disease), and in 11 patients with ulcerative colitis (seven with active disease). RESULTS: The median gastric pH values in the patient groups (Crohn's disease 2.4, range 1.5-4.1; ulcerative colitis 1.95, range 1.55-4.4) were significantly higher than those observed in the controls (1.55, range 0.95-2.6). In the small bowel and colonic segments, all the pH values of Crohn's disease patients were comparable to those of the controls, as were the pH values in the proximal small intestine and in the left colon in patients with ulcerative colitis. However, the latter group had higher pH values in the terminal ileum, the caecum and the right colon. Patients with active disease had comparable median gastrointestinal pH values to patients in remission. CONCLUSIONS: The luminal release of 5-amino salicylic acid might not be inhibited by low pH in patients with active inflammatory bowel diseases. This supports a safe disintegration of the slow release mesalazine preparations even in the presence of severe disease.     

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.     

Effect of chronic nicotine administration on trinitrobenzene sulphonic acid-induced colitis

BACKGROUND: Smoking, probably due to nicotine, has a bivalent effect on inflammatory bowel disease, ameliorating disease activity in ulcerative colitis and with a deleterious effect on Crohn's disease. The effect of nicotine patches in ulcerative colitis is controversial. AIM: To investigate the effect of chronic nicotine use in a rat model of colitis. METHODS: Colitis was induced in Sprague-Dawley rats by rectal administration of 30 mg trinitrobenzene sulphonic acid (TNBS) in 50% ethanol. Nicotine was dissolved in drinking water (2.5, 12.5, 25 and 250 microg/ml), with rats drinking ad libitum. Nicotine administration started 10 days prior to damage induction and had no effect on weight gain or daily food intake of rats. Rats were sacrificed 1 and 5 days after TNBS administration, their colons resected, rinsed, weighed, damage assessed macroscopically (mm2) and microscopically and tissue processed for myeloperoxidase (MPO) and nitric oxide synthase (NOS) activities, leukotriene B4 (LTB4), prostaglandin E2 (PGE2) generation and interleukin-1 (IL-1) serum levels. RESULTS: Nicotine, by itself, caused no damage to the colon. Nicotine had a dose-dependent bivalent effect on colitis, significantly reducing macroscopic damage from 983 +/- 10 mm2 on TNBS alone to 429 +/- 118 mm2 on TNBS plus 12.5 microg/ml of nicotine, and escalating to 1086 +/- 262 mm2 on 250 microg/ml of nicotine. Segmental weight declined significantly (from 2.4 +/- 0.2 to 1.65 +/- 0.20 g/10 cm), on 12.5 microg/ml nicotine, as did MPO activity (from 3.2 +/- 0.4 to 0.7 +/- 0.1 units/g). All these parameters returned to the levels of TNBS alone when the dose of nicotine was increased to 250 microg/ml. Nicotine had no effect on NOS activity, PGE2 generation and serum IL-1 levels, but increased LTB4 generation. CONCLUSIONS: Nicotine has a dose-dependent bivalent effect on TNBS-induced colitis which is not due to reduction in IL-1 serum levels or PGE2 generation, and is not NOS-mediated.     

Abnormal mucosal glycoprotein synthesis in inflammatory bowel diseases is not related to cigarette smoking

Patients with ulcerative colitis are usually non- or ex-smokers in contrast to Crohn's disease where smoking is common. Abnormalities of quantity and quality of intestinal mucus have been postulated in the pathogenesis of these diseases. It is possible that smoking habit may exert its effects via changes in mucus in inflammatory bowel disease. We have therefore studied incorporation of N-acetylglucosamine into synthesized colonic mucin in explants from 85 controls with normal colonoscopic appearances and histology, including 27 smokers and 58 nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn's disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into normal explants was 31.3 +/- (SD) 7.1 dpm/microgram biopsy protein, incorporation was increased in patients with active Crohn's disease (mean 41.2 +/- (SD) 10.4 dpm/microgram biopsy protein, p = 0.003), decreased in inactive ulcerative colitis (mean 24.1 +/- 7.8 dpm/microgram biopsy protein, p = 0.0006) but normal in active ulcerative colitis (mean 35.0 +/- 13.8 dpm/microgram biopsy protein, p = 0.44). No significant relationship was found between cigarette smoking habits and mucus synthesis in controls with normal mucosa (nonsmokers, n = 58, mean 31.0 +/- (SD) 7.52 dpm/microgram biopsy protein; smokers, n = 27, mean 31.8 +/- (SD) 6.1 dpm/microgram biopsy protein, p = 0.9). This study shows that mucus glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to normal levels in active disease and that synthesis is increased in Crohn's disease. There is no effect of smoking on mucus synthesis by control biopsies suggesting that the differences seen in inflammatory bowel disease are not related to cigarette smoking.     

Aneurysmal bone cyst involving the distal phalanx of a child

BACKGROUND: The synthesis of nitric oxide (NO) in the colonic mucosa of patients affected by ulcerative colitis (UC) has been previously investigated using indirect measurements of enzyme activity and non-specific measurements of luminal NO gas. The aim of this study was to determine unequivocally if luminal NO gas in active UC is present in greater concentrations than in healthy control subjects. METHODS: Luminal gas was collected from eight patients with active UC and eight healthy volunteers. NO gas concentration was measured using diode laser spectroscopy. RESULTS: NO gas was detected in four of eight patients with active UC (range 0.13-1.1 nmol) and none of the healthy control subjects. CONCLUSION: NO gas is present in greater concentrations in patients with active UC than in control subjects. This supports the view that mucosal NO synthesis is increased in ulcerative colitis.     

Measurement of rectal blood flow by laser Doppler flowmetry in inflammatory bowel disease

BACKGROUND/AIMS: Vascular alterations have been suggested as pathogenic factors in inflammatory bowel disease, particularly Crohn's disease. The aim of our study was to assess rectal blood flow in patients with active inflammatory bowel disease involving the rectum. METHODOLOGY: Endoscopic measurement of rectal blood flow was performed by laser Doppler flowmetry in 45 subjects divided into three groups: healthy controls, ulcerative colitis and rectal Crohn's disease. RESULTS: Rectal perfusion was found to be significantly impaired in patients with ulcerative colitis, but not in those with Crohn's colitis. CONCLUSIONS: Our results confirm the role of local ischemia in ulcerative colitis, but do not support the theory that vascular factors play a key role in the pathogenesis of Crohn's disease.     

Pre-mRNA processing enhancer (PPE) element increases the expression of an intronless thymidylate synthase gene but does not affect intron-dependent S phase regulation

Maternal smoking during pregnancy causes reduction of fetal breathing movements, an effect attributed to nicotine in fetal blood. Nicotine is metabolized to cotinine which has a long plasma half-life and exhibits slow clearance across membrane barriers. It is also known to activate placental phospholipase-A2-like enzymes, resulting in formation of prostaglandins. Therefore, we studied transport of nicotine in isolated perfused cotyledon of normal human term placenta. The placental cotyledon was perfused with aerated (21% O2, 5% CO2) Krebs-Ringer bicarbonate buffer (pH 7.4, 37 degrees C) containing 2% albumin on both maternal (230 ml, 15 ml/min, 35 mm Hg) and fetal (93 ml, 1.75 ml/min, 70 mm Hg) sides in a closed recirculating system. Nicotine (2 mg) was added to the maternal perfusate; perfusate samples (1 ml) were collected from both sides at regular intervals and analyzed for nicotine and cotinine by high-pressure liquid chromatography. This study gave the following results: (1) In about 60-80 min, 18.6% of the nicotine added to the maternal perfusate was transferred to the fetal perfusate, and the maternal/fetal concentration ratio reached 1.0. These results show rapid placental transfer of nicotine, consistent with its high lipid solubility. (2) Less than 1% is metabolized to cotinine in placenta. The ratio of cotinine concentrations in maternal and fetal perfusates reached 1.0 in about 40 min. These studies were also verified using 14C-nicotine. (3) Maximal reduction in fetal breathing movements occurs at about 30 min, and recovery occurs at 90 min after tobacco smoking by the mother. These observations agree with the rate of placental transfer of nicotine. (4) When nicotine was added on the fetal side, part of it was metabolized to cotinine. However, the maximal concentration of cotinine was twice higher on fetal than on maternal side. These observations suggest that accumulation of cotinine on fetal side may activate prostaglandin formation and trigger spontaneous abortions in pregnant smokers.     

A double-blind comparison of oral versus rectal mesalamine versus combination therapy in the treatment of distal ulcerative colitis

OBJECTIVES: The aim of this study was to compare the efficacy of mesalamine rectal suspension enema (Rowasa) alone, oral mesalamine tablets (Asacol) alone, and the combination of mesalamine enema and mesalamine tablets in patients with active mild-to-moderate distal ulcerative colitis. METHODS: Sixty outpatients with ulcerative colitis at least 5 cm above the anal verge and not more than 50 cm, inclusive, and a total disease activity index (DAI) score between 4 and 10, inclusive, were randomized to either mesalamine rectal enema (n = 18) once nightly, oral mesalamine 2.4 g/day (n = 22), or a combination of both treatments (n = 20). Placebo capsules and enemas were used to maintain a blind procedure. Total DAI scores and abbreviated DAI scores were evaluated at wk 3 and 6, and wk 1 and 2, respectively. Patients recorded the amount of blood in stools, urgency, straining at stools, and abdominal pain in daily diaries. Physicians and patients rated overall improvement at each visit. RESULTS: At wk 6, combination therapy produced a greater improvement (-5.2) in total DAI scores than did either mesalamine enema (-4.4) or mesalamine tablet (-3.9) therapy alone; similar treatment differences were observed at wk 3. Compared with patients given mesalamine enemas or mesalamine tablets, combination-therapy patients reported an absence of blood in stools significantly sooner and, at all visits, the combination therapy group had the highest percentage of patients who reported no blood in their stools. Physicians' and patients' ratings of improvement indicated that combination therapy significantly improved disease status, compared with mesalamine tablet therapy alone. All treatments were well tolerated. CONCLUSIONS: The combination of oral and rectal mesalamine therapy was well tolerated and produced earlier and more complete relief of rectal bleeding than oral or rectal therapy alone.     

The radiological differentiation between ulcerative and granulomatous colitis by double contrast radiology

The purpose of this report is to illustrate the value of the double contrast technic for the detection of early changes of colitis and for the differentiation between ulcerative and granulomatous colitis. Fifty consecutive patients with radiologically-diagnosed nonspecific colitis are included and the radiographs, endoscopic and pathologic reports and photographs were reviewed. On radiological grounds ulcerative colitis were diagnosed in 23 patients and granulomatous colitis in 27 patients. There were no radiologically indeterminate cases. Follow-up information was obtained by colectomy in nine patients, colonoscopy in nine patients and sigmoidoscopy in the remainder. In no case did the endoscopic or pathologic diagnosis conflict with the radiological diagnosis. With the double contrast technic, very fine mucosal detail can be seen including features such as granular mucosa, "aphthoid" ulcers and discontinuous disease which are not demonstrable by the conventional single contrast barium enema. This detailed mapping of the nature and extent of disease facilitates the differential diagnosis between ulcerative and granulomatous colitis.     

X-ray symptoms in ulcerative colitis

Barium enema studies in 200 patients with ulcerative colitis were analyzed according to radiological symptoms. The results of the radiological examination were compared with those of rectoscopy and biopsy. In about 75 per cent of patients good agreement was achieved.     

Surgery for inflammatory bowel disease in Singapore

Inflammatory bowel disease is uncommon in Asians and reports of surgery in these populations are rare. Eighty-two patients with inflammatory bowel disease were seen in the Department of Colorectal Surgery over a five-year period (1989-1994). Twenty-three patients underwent surgery for their disease. There were 12 males and 11 females with 16 Chinese, 4 Indians and 3 Malays. Twelve had Crohn's disease and 11, ulcerative colitis. The majority of patients with Crohn's disease had emergency surgery for bleeding, perforation, abdominal masses and intestinal fistulae. Fifty percent of these had the diagnosis made intraoperatively or post-operatively. Surgery for ulcerative colitis was indicated because of multiple relapses, non-response to medical treatment, side effects of therapy or malignant change. The median age at surgery of patients with Crohn's disease and ulcerative colitis was 39 years (range 24-84) and 40 (range 18-60) respectively. The median follow-up was 22.4 months (range 9-50). The results of surgical therapy in these patients show that surgery when indicated can be done with minimum morbidity and mortality.     

Human immunodeficiency virus and resistance]

CONTEXT: Racial differences in tobacco-related diseases are not fully explained by cigarette-smoking behavior. Despite smoking fewer cigarettes per day, blacks have higher levels of serum cotinine, the proximate metabolite of nicotine. OBJECTIVE: To compare the rates of metabolism and the daily intake of nicotine in black smokers and white smokers. DESIGN: Participants received simultaneous infusions of deuterium-labeled nicotine and cotinine. Urine was collected for determination of total clearance of nicotine and cotinine, fractional conversion of nicotine to cotinine, and cotinine elimination rate. Using cotinine levels during ad libitum smoking and clearance data, the daily intake of nicotine from smoking was estimated. SETTING: Metabolic ward of a university-affiliated public hospital. PARTICIPANTS: A total of 40 black and 39 white smokers, average consumption of 14 and 14.7 cigarettes per day, respectively, of similar age (mean, 32.5 and 32.3 years, respectively) and body weight (mean, 73.3 and 68.8 kg, respectively). MAIN OUTCOME MEASURES: Clearance (renal and nonrenal), half-life, and volume of distribution of nicotine and cotinine and the calculated daily intake of nicotine. RESULTS: The total and nonrenal clearances of nicotine were not significantly different, respectively, in blacks (17.7 and 17.2 mL x min(-1) x kg(-1)) compared with whites (19.6 and 18.9 mL x min(-1) x kg(-1)) (P=.11 and .20). However, the total and nonrenal clearances of cotinine were significantly lower, respectively, in blacks (0.56 and 0.47 mL x min(-1) x kg(-1)) than in whites (0.68 vs 0.61 mL x min(-1) x kg(-1); P=.009 for each comparison). The nicotine intake per cigarette was 30% greater in blacks compared with whites (1.41 vs 1.09 mg per cigarette, respectively; P=.02). Volume of distribution did not differ for the 2 groups, but cotinine half-life was higher in blacks than in whites (1064 vs 950 minutes, respectively; P = .07). CONCLUSIONS: Higher levels of cotinine per cigarette smoked by blacks compared with whites can be explained by both slower clearance of cotinine and higher intake of nicotine per cigarette in blacks. Greater nicotine and therefore greater tobacco smoke intake per cigarette could, in part, explain some of the ethnic differences in smoking-related disease risks.     

Cytokine production from colonic T cells in patients with ulcerative colitis with and without primary sclerosing cholangitis

PURPOSE: Only five percent of all patients with ulcerative colitis develop primary sclerosing cholangitis. T cells accumulate at the sites of the colonic and bile duct inflammation in both ulcerative colitis and primary sclerosing cholangitis. T helper cell populations comprise functionally distinct subsets characterized by the cytokines they produce. Several alterations in cytokine production have been described in patients with ulcerative colitis. The aim of this study was to investigate possible differences in T helper subsets and cytokine production in peripheral blood and colonic mucosa among ulcerative colitis patients with and without primary sclerosing cholangitis. METHODS: Eleven patients with primary sclerosing cholangitis and extensive ulcerative colitis, 11 patients with extensive ulcerative colitis and no liver disease, and 5 patients without any history of liver disease who underwent routine colonoscopy because of previous polypectomy were included in the study. Colonoscopy with multiple biopsies was performed on all patients. Lamina propria mononuclear cells and peripheral blood mononuclear cells were isolated. A modified version of solid-phase enzyme-linked immunospot assay was used for the separate counting of cells producing interferon-gamma, interleukin-2 (T helper 1), and interleukin-4 (T helper 2). RESULTS: No differences in spontaneous production of cytokines from peripheral blood mononuclear cells was found among the three groups. Patients with primary sclerosing cholangitis compared with patients with ulcerative colitis without liver disease showed a significant increase in the number of cells secreting interferon-gamma after purified protein derivative stimulation (P < 0.02). More cells secreting interferon-gamma were found in the two ulcerative colitis groups than in the cell populations from healthy controls (P < 0.03). The number of cells secreting interferon-gamma in the primary sclerosing cholangitis group was significantly lower than in the ulcerative colitis group without liver disease (P < 0.04). The number of cells secreting interleukin-4 was lower in the primary sclerosing cholangitis group than among the patients with ulcerative colitis only (P = 0.05). CONCLUSION: Isolated lymphocytes from colonic mucosa differ in cytokine production in patients with ulcerative colitis with and without primary sclerosing cholangitis.     

Pharmacokinetics and retrograde colonic spread of budesonide enemas in patients with distal ulcerative colitis

METHODS: The retrograde spread of two budesonide enema formulations with different viscosities was investigated. The study design was open, randomized and two-period crossover. Three female and two male patients (age range: 35-45 years) with distal ulcerative colitis or proctitis participated. Both enema formulations contained a dose of 2 mg budesonide/100 mL. An unabsorbable radioactive marker (99mTc-labelled human serum albumin microcolloid) was added to the enema just before administration. All doses were given in the evening with the patients lying in a supine position during the whole investigation. The intestinal spread was followed for 8 h using scintigraphic imaging. Plasma samples for budesonide assay were taken during the 12 h after administration of the low viscosity enema. RESULTS: Budesonide plasma levels were measurable for up to 4-6 h. Cmax was 2.5 nmol/L (range: 0.9-4.5 nmol/L) and was attained in 1.5 h (range 1-3 h). The patients had no difficulty in retaining the enemas. There was a statistically significant difference in spread between the low and high viscosity enema. The low viscosity enema spread over an area situated between the rectum and the splenic flexure. The spread occurred mainly in the first 15 min after administration. In contrast, the high viscosity enema, in most cases, spread only over a minor part of this area and the rate and extent of spreading was also more variable with this formulation. CONCLUSION: The spread of a low viscosity enema appears to be well suited for the treatment of proctitis and distal colitis.     

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.