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.     

Rat big endothelin-1-induced bronchoconstriction and vasoconstriction in the isolated perfused rat lung: role of endothelin converting enzyme and neutral endopeptidase 24.11

We encountered two chemotherapy cases related to anticancer drug-induced colitis. Case 1 was a 35-yo-female with a recurrence of ovarian cancer. She was treated with intraarterial infusion consisting of continuous 5-fluorouracil (250 mg/day 5 days/week x 4) following low-dose consecutive cisplatin (20 mg/day 5 days/ week x 1). The catheter was inserted into the abdominal aorta about 2 cm above the carina of the common iliac arteries. Six weeks after the start of chemotherapy, severe abdominal pain and melena occurred. Case 2 was a 68-yo-female with an endometrial cancer recurrence. The same intraarterial chemotherapy used in case 1 was was initiated. Four weeks after the start of chemotherapy, before intraarterial infusion of CDDP, she suffered from constipation and than diarrhea, abdominal pain and melena. Both cases were diagnosed as anticancer drug-induced colitis with the pathological findings from colon biopsy and the clinical course, and improved in about 1 month with the discontinuation of intraarterial infusion, fasting and TPN. Intraarterial infusion of only CDDP caused both patients no intestinal symptoms, so it is supposed that intraarterial infusion of 5-fluorouracil induced the colitis. Anticancer drug-induced colitis should be taken into consideration as a rare but possible course of chemotherapy-related complication with intraarterial infusion of 5-fluorouracil.     

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.     

Network of inflammatory cytokines and correlation with disease activity in ulcerative colitis

OBJECTIVE: The inflammatory component of most human inflammatory chronic diseases implicates the production of proinflammatory cytokines. Tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL1beta) seem to play an important role in ulcerative colitis (UC) in relevant experimental models. Moreover, antiTNF therapy seems promising experimentally and clinically. However, these cytokines, and TNFalpha more particularly, are hardly seen in vivo in such patients. The mediators of choice, correlated with disease activities or drug efficacy, remain unclear. To characterize in vivo the network of colonic cytokines in patients with UC, and the contribution of the various cytokines to disease activity we performed this study, using the colonic perfusion method. METHODS: A 20-cm colon length was perfused. Perfusate samples were collected for cytokine determination by enzyme-linked immnoassays. Nineteen perfusions were performed in mild to moderate UC, including two successive perfusions in four patients. Six healthy control patients and four having Crohn's disease (CD) with rectal involvement were studied. Endoscopic score, leukocyte scintigraphy, and systemic markers of inflammation were simultaneously quantified. RESULTS: Large amounts of IL1beta, TNFalpha, IL6, and IL8 were produced in UC patients with a highly significant correlation between TNFalpha, IL1beta and IL8 two by two. Multivariate factorial analysis indicated that IL1beta showed the best correlation with disease activity. Locally produced IL6 was strongly associated with circulating platelet counts. Moreover, production of inflammatory cytokines was associated with similar variations of disease activity in the four patients with two successive perfusions performed. The level of inflammatory cytokines in CD was lower than in UC; TNFalpha, IL1beta, and IL6 were not found in any control patients. CONCLUSION: UC appears to be a chronic inflammatory disease characterized by high production of all four proinflammatory cytokines (IL1beta, TNFalpha, IL6, and IL8). These results suggest that colonic perfusion may be a suitable method to evaluate the local anticytokine properties of new drugs, in correlation with disease activity and systemic markers of inflammation.     

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.     

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.     

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.     

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 role of smoothing techniques in the interpretation of results from genomic scans using sib-pair data

BACKGROUND: Budesonide, a corticosteroid with high topical anti-inflammatory activity and low systemic activity, has been shown to prolong time to relapse in Crohn's disease. In the present study, the efficacy of budesonide in an oral pH-modified-release formulation was evaluated for maintenance treatment in patients with steroid-dependent ulcerative colitis. METHODS: Fourteen patients with steroid-dependent ulcerative colitis in the reduction phase of conventional glucocorticosteroids (c-GCS) following a severe attack, were treated with budesonide 3 mg t.d.s. for 6 months. The primary investigation parameters were changes in the clinical activity index (CAI) and in the daily dose of c-GCS. RESULTS: In 11 cases the CAI improved significantly and treatment with c-GCS could be terminated. Three patients experienced relapse and needed further c-GCS treatment. The average daily dose of c-GCS and the average value of the CAI before treatment with budesonide were significantly higher in the relapse group than in the remission group. CONCLUSIONS: In patients with c-GCS-dependent ulcerative colitis, a dose of 9 mg budesonide daily in an oral pH-modified-release formulation was well tolerated, significantly decreased the CAI, and rendered c-GCS unnecessary in the majority of cases.     

Hormonal profiles of early gestations with abnormal karyotype

OBJECTIVE: To describe the hormonal profiles of chromosomally abnormal pregnancies during the first trimester. DESIGN: A prospective study from 1984 through 1990 in which infertility patients who conceived were monitored weekly with serum E2, P, and beta-hCG levels. SETTING: The infertility practice at Rush-Presbyterian-St. Luke's Medical Center in Chicago, Illinois. PATIENTS: Study included 15 women who had dilatation and curettage for first trimester fetal losses with confirmed abnormal karyotype, 6 women with chromosomally normal male abortuses, and 60 consecutive women whose pregnancies yielded normal term infants. RESULTS: After natural conception, E2 demonstrated a moderate rise in both normal and chromosomally abnormal pregnancies to approximately 300 pg/mL by day 29 (6 weeks of gestation). In normal gestations, E2 continued a steady increase to exceed the level of 1,000 pg/mL by day 64 (11 weeks of gestation). In chromosomally abnormal pregnancies, the mean E2 plateaued and remained at approximately 200 pg/mL until fetal demise was noted. In stimulated conceptions, the rise of E2 was sharp and early (1,200 pg/mL by day 29); in normal pregnancies, E2 steadily increased to an average of 1,400 pg/mL by the end of the first trimester, whereas in karyotypically abnormal gestations, E2 declined to approximately 200 pg/mL by day 64. In pregnancies yielding a male abortus, a sharp decline and plateau at 800 pg/mL by day 56 (10 weeks of gestation) was observed. In both natural and stimulated normal pregnancies, hCG levels first demonstrated a linear rise, followed by a curvilinear increase from day 29 until day 56, with a peak of approximately 110,000 mIU/mL. The beta-hCG in chromosomally abnormal pregnancies, as well as in pregnancies yielding a male abortus, was characterized by a slow and gradual rise to a maximum of 40,000 mIU/mL, which remained relatively linear until day 64 when fetal demise was detected in all cases. Progesterone level data were excluded from analysis because of frequent P supplementation. CONCLUSIONS: There were significant differences in the hormonal profiles of chromosomally normal and abnormal pregnancies. Serial measurements of serum E2 and beta-hCG from the 6th week of gestation may be useful in predicting an abnormal karyotype sooner than other current diagnostic tests.     

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.     

Changes in plasma and colonic mucosa fatty acid profiles in rats with ulcerative colitis induced by trinitrobenzene sulfonic acid

Polyunsaturated fatty acids have a key role in the pathogenesis of inflammatory bowel disease since some of the arachidonic acid-derived eicosanoids have been found to be increased in inflamed intestinal mucosa in the acute phase of human disease. The aim of this study was to prospectively assess plasma and colon mucosa fatty acid patterns in rats with experimental ulcerative colitis. Twenty rats were treated with trinitrobenzene sulfonic acid and 20 with NaCl; two groups were killed after one week and two after two weeks to evaluate colon damage. Plasma was obtained by aortic puncture and colonic mucosa was scraped off and the fatty acid pattern was determined by gas-liquid chromatography. Total, saturated, and monounsaturated plasma fatty acids were significantly higher in both periods of ulcerative colitis as compared to controls. Plasma n-6 fatty acids were increased after treatment, but no significant changes were observed concerning to n-3 fatty acids. With regard to colon mucosa, saturated and monounsaturated fatty acids did not change because of the disease; however, n-6 fatty acids decreased in the first week and increased in the second week and n-3 fatty acids were increased. Changes on the fatty acid distribution in plasma did not parallel to those of colonic mucosa except for 22:6(n-3). We have also found that experimental ulcerative colitis induced by trinitrobenzene sulfonic acid reproduces many of the features related to changes in plasma and colon mucosa fatty acids observed in the human disease.     

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.     

The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts

BACKGROUND & AIMS: Crohn's disease and ulcerative colitis show a familial aggregation. In both diseases, anti-goblet cell autoantibodies (GABs) have been described. The aim of this study was to define the role of GABs in the pathogenesis of inflammatory bowel disease. METHODS: The study population comprised 61 patients with ulcerative colitis, 76 patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 105 first-degree relatives of patients with Crohn's disease. Thirty-five patients with infectious enterocolitis and 56 healthy unrelated subjects served as controls. Autoantibodies were detected by indirect immunofluorescence. RESULTS: Thirty-nine percent of patients with ulcerative colitis (24 of 61) and 30% of patients with Crohn's disease (23 of 76) were positive for GABs. GABs were detected in 21% (21 of 101) of first-degree relatives of patients with ulcerative colitis and in 19% (20 of 105) of first-degree relatives of patients with Crohn's disease. In patients with infectious enterocolitis and in healthy controls, GABs were seen in 3% (1 of 35) and 2% (1 of 56), respectively. The differences between control groups and both groups of patients or their first-degree relatives were significant. CONCLUSIONS: The high prevalence in first-degree relatives suggests that GABs may represent a marker characterizing susceptibility to inflammatory bowel disease.     

Suppressibility of plasma adrenocorticotropin by hydrocortisone: potential usefulness in the diagnosis of Cushing's disease

Repeatedly normal cortisol suppressibility by dexamethasone in 2 patients with Cushing's disease led to the present study of the prevalence of this phenomenon in 58 patients with otherwise incontrovertible evidence of Cushing's disease. Because as many as 23% of these patients manifested this phenomenon, we investigated the suppressibility of plasma ACTH: 1) during i.v. infusion of hydrocortisone, after a priming dose (7 mg), at 3 mg/h in 8 patients and 8 normal controls; and 2) for 2 h, after oral hydrocortisone, 0.25 mg/kg, in 13 patients and 16 controls. The data showed invariable suppression of plasma ACTH to < or = 10 pg/mL (< or = 2.2 pmol/L) after 120 min of the infusion or at 90 min after oral hydrocortisone in 16 fasting normal subjects given oral hydrocortisone between 0800 and 0830 h. Plasma ACTH exceeded 10 pg/mL (2.2 pmol/L) at the same times in 14/14 patients with active Cushing's disease, including 3 patients whose cortisol suppressibility by dexamethasone had been misleadingly normal and in 4/7 patients with intermittent hypercortisolism. Occasional variations in plasma cortisol elevations after the oral dose require that plasma cortisol concentration be monitored at 60 min after the oral hydrocortisone dose, because the present evidence supports the validity of the conclusion that a plasma ACTH concentration below 10 pg/mL excludes Cushing's disease only when plasma cortisol concentration at 60 min lies between 16 and 38 microg/dL. Further evaluation of ACTH suppressibility by cortisol would be worthwhile, to confirm its potential value in facilitating positive diagnosis of Cushing's disease when dexamethasone suppressibility seems misleading.     

Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss

In view of the recent demonstration that obesity in animals and humans is associated with an increase in tumor necrosis factor-alpha (TNFalpha) expression, that this expression falls with weight loss, and that TNFalpha may specifically inhibit insulin action, the possibility that TNFalpha may be a mediator of insulin resistance has been raised. We have undertaken this study to investigate whether serum TNFalpha concentrations are elevated in obese subjects, whether they fall after weight loss, and whether this fall parallels the fall in insulin release after glucose challenge. Obese patients (age range: 25-54, weight mean +/- SD: 96.4 +/- 13.8 kg, body mass index: 35.7 +/- 5.6 kg/m2) were started on a diet program. The mean weight fell to 84.5 +/- 11.3 (P < 0.0001) and body mass index to 31.3 +/- 4.9 (P < 0.0001). Plasma TNFalpha concentrations were markedly elevated in the obese (3.45 +/- 0.16 pg/mL), when compared with controls (0.72 +/- 0.28 pg/mL), and fell significantly (2.63 +/- 1.40 pg/mL) after weight loss (P < 0.02). The magnitude of insulin release after glucose (75 g) challenge (area under the curve) also fell significantly (P < 0.01) after weight loss. The magnitude of weight loss and fall in TNFalpha were related to basal body weight (r = 0.57, P < 0.001) and basal TNFalpha (r = 0.55, P < 0.001) concentrations, respectively, but not to each other or to the glucose-induced insulin release (area under the curve). We conclude that obesity is associated with increased plasma TNFalpha concentrations, which fall with weight loss. Because circulating TNFalpha may mediate insulin resistance in the obese, a fall in TNFalpha concentrations may contribute to the restoration of insulin resistance after weight loss, Thus, TNFalpha may be an important circulating cytokine, which may provide a potentially reversible mechanism for mediating insulin resistance.     

Neutrophil signaling alteration: an adverse inflammatory response after burn shock

BACKGROUND: Perinuclear antineutrophil cytoplasmic antibodies occur frequently in adult patients with chronic pouchitis after colectomy and ileal pouch-anal anastomosis for ulcerative colitis. The purpose of the study was to determine the prevalence of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in children and adolescents who undergo colectomy and ileal pouch-anal anastomosis for ulcerative colitis and familial adenomatous polyposis. METHODS: Five groups of children and adolescents (age, <20 years) were studied, with the following histories: acute pouchitis and history of ulcerative colitis; chronic pouchitis and history of ulcerative colitis; pouchitis with Crohn's disease features and a history of ulcerative colitis; no pouchitis and a history of ulcerative colitis; and familial adenomatous polyposis, with or without pouchitis. Antineutrophil cytoplasmic antibody levels and titers were detected in postoperative sera by enzyme-linked immunosorbent assay, and positive results were subtyped by indirect immunofluorescence. RESULTS: The frequency of perinuclear antineutrophil cytoplasmic antibodies and cytoplasmic antineutrophil cytoplasmic antibody in patients with a history of ulcerative colitis were 67% and 15%, compared with a 0% presence in patients with familial adenomatous polyposis (p < 0.001). There was no significant correlation between the frequency of perinuclear antineutrophil cytoplasmic antibodies and ulcerative colitis patient subgroups (patients with and without pouchitis, 66% and 75%). Similarly, there was no significant correlation between the frequency of cytoplasmic antineutrophil cytoplasmic antibodies among ulcerative colitis patient subgroups (patients with and without pouchitis, 19% and 8%). The frequency of cytoplasmic antineutrophil cytoplasmic antibody in patients with Crohn's disease features (50%), was increased, but this difference was not significant. CONCLUSIONS: There is a high frequency of perinuclear antineutrophil cytoplasmic antibodies in children and adolescents who undergo ileal pouch-anal anastomosis for ulcerative colitis, whether or not they have pouchitis. The frequency of cytoplasmic antineutrophil cytoplasmic antibody is lower in this patient population. Additional studies will be required to determine whether the presence of cytoplasmic antineutrophil cytoplasmic antibody is associated with the postoperative development of features of Crohn's disease.     

Recognition of bactericidal/permeability-increasing protein by perinuclear anti-neutrophil cytoplasmic antibody-positive sera from ulcerative colitis patients: prevalence and clinical significance

BACKGROUND: The aim of this study was to evaluate a) the role of bactericidal/permeability-increasing protein (BPI) as a possible antigen determining perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) reactivity in ulcerative colitis and b) the prevalence and clinical correlates of anti-BPI antibodies in patients with ulcerative colitis on the basis of their p-ANCA status. METHODS: p-ANCA and anti-BPI antibodies were evaluated by means of indirect immunofluorescence and enzyme-linked immunosorbent assay methods in a group of 112 ulcerative colitis patients (including 42 patients subjected to proctocolectomy) well defined as far as their clinical features and p-ANCA status. RESULTS: Anti-BPI antibodies were detected in 24% of non-operated patients and were significantly more frequent in p-ANCA-positive patients (32% versus 5% in p-ANCA-negative patients; P < 0.015). The prevalence of anti-BPI antibodies was similar in non-operated and operated patients and was high in men, in patients with an extensive and aggressive disease, and in patients developing pouchitis after surgery. CONCLUSIONS: These data indicate that BPI is a neutrophil antigen frequently recognized by p-ANCA-positive ulcerative colitis sera. The presence of anti-BPI antibodies appears to identify further immunologic and clinical heterogeneity in ulcerative colitis.     

The safety of transurethral prostatectomy: a cohort study of mortality in 9,416 men

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCAs) from patients with vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs with a perinuclear pattern of immunofluorescence are found in most patients with ulcerative colitis, but several findings are against ANCAs having a pathogenetic role in this disease. AIMS: To evaluate the influence of ANCAs associated with ulcerative colitis on the respiratory burst activity of neutrophils. PATIENTS: Serum samples were obtained from 14 patients with ulcerative colitis, seven of whom showed positivity for p-ANCAs, three patients with vasculitidis, two with positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers. METHODS: A positive ANCA serology was determined with a standard indirect immunofluorescence assay. Purified immunoglobulins (IgGs) were prepared from serum samples by DEAE-Affigel blue chromatography. Human neutrophils were prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-.) generation was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome. RESULTS: There were no significant differences among samples from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA negative patients, and controls on O2-. production, whereas ANCA positive IgG from vasculitidis significantly enhanced O2-. release (p < 0.001). CONCLUSIONS: p-ANCAs associated with ulcerative colitis have no effect on the respiratory burst activity of normal human neutrophils in vitro. These results reinforce the hypotheses that ANCAs are unlikely to contribute to the pathogenesis of ulcerative colitis.     

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.