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J Brynskov

Publications and source records attributed to J Brynskov.

At least 37 records · Page 2Linked to original sources
PubMed1996

A simple filter-paper technique allows detection of mucosal cytokine levels in vivo in ulcerative colitis. Interleukin-1 and interleukin-1-receptor antagonist.

A simple filter-paper method for in vivo assessment of cytokines in intestinal mucosa of patients with ulcerative colitis (UC) was developed and evaluated. Twenty-eight patients were included. Twenty-three patients had ulcerative colitis (UC) and five irritable bowel syndrome (IBS). Inflammation was assessed endoscopically. Through a rectoscope, filter paper was applied to the macroscopically most inflamed area of the rectal mucosa until soaked. The filter paper was transferred to a buffer solution, and IL-1 beta and IL-1ra were assessed using ELISA. Positive correlations between endoscopic grading and In(IL-1 beta) (P < 0.0001) and In(IL-1ra) (P < 0.001) and a negative correlation between endoscopic grading and In(IL-1ra /IL-1 beta) (P < 0.02) were found. In measurements during and after a flare-up no significant change in IL-1ra but a significant decrease in IL-1 beta was detected, which is in agreement with investigations on biopsies. In conclusion, the filter-paper technique is an easily applicable, low-risk method that provides a means of monitoring cytokines in vivo in UC.

Colitis, Ulcerative↗
PubMed1996

Increased mucosal concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), sE-selectin, and interleukin-8 in active ulcerative colitis.

Cell surface adhesion molecules (CAM) are important promotors of the immunoinflammatory cascade. The circulating levels of soluble intercellular adhesion molecule 1 (ICAM-1) have previously been shown to correlate with disease activity in inflammatory bowel disease. The primary aim of this study was consequently to investigate if this also applies to mucosal levels of soluble ICAM-1. We measured soluble ICAM-1 levels in intestinal biopsy specimens and the endoscopic activity of 69 patients with ulcerative colitis (UC) and 14 controls and found that the median concentration of soluble ICAM-1 was significantly higher in patients with moderately or very active UC (15.0 ng/ml) as compared to slightly active (9.8 ng/ml) and inactive UC (9.5 ng/ml) as well as controls (6.5 ng/ml) (P < 0.005). To further elucidate the interactions, two other CAM [E-selectin and vascular cellular adhesion molecule 1 (VCAM-1)], together with interleukin-8 (IL-8), IL-2 receptor (IL-2R) alpha and beta chains, were also measured. A significant trend towards higher soluble E-selectin levels in biopsies with active UC (1.8 pg/ml) as compared to inactive UC (1.3 pg/ml) and to controls (< 1.0 pg/ml) (P < 0.01) was also found. In contrast, soluble VCAM-1 was barely detectable in biopsies from two UC patients. A significant correlation was found between soluble ICAM-1 and IL-8 concentrations (r = 0.46; P < 0.0001), and between sICAM-1 and sIL-2R alpha concentrations (r = 0.69; P < 0.0001), while sIL-2R beta was not detected. This study shows that intestinal ICAM-1 and E-selectin correlate with endoscopic activity of UC and with IL-8 and IL-2R alpha levels. These mediators may be useful in monitoring mucosal inflammation in studies exploring the therapeutical potential of targeting CAM. The lack of detectable VCAM-1, which is induced only in venous endothelium is interesting. It may suggest that intestinal inflammation mainly affects arterial endothelial cells and support the theory that intestinal vasculitis is involved in the pathogenesis of inflammatory bowel disease.

Acute Disease↗
PubMed1996

Clinical pharmacology in gastroenterology: development of new forms of treatment of inflammatory bowel disease.

Kinetic-dynamic aspects of the development of slow-release mesalazine, Pentasa (now an established treatment of inflammatory bowel disease (IBD)), and cyclosporin, a T cell selective immunosuppressant (still in the investigative phase), are reviewed as examples of Danish contributions at an early stage to international, clinical drug research. Apart from increasing the therapeutic options for patients with IBD, current and future studies with these (and other) drugs may add important clues to a more precise understanding of the basic pathogenetic mechanisms (e.g. cytokines, adhesion molecules) involved in these diseases. The future development and clinical implementation of novel drug designs in IBD and other gastrointestinal diseases may be expected to benefit from a continued or even closer collaboration between clinical gastroenterologists and basic research institutions, including the pharmaceutical industry at an early stage.

Aminosalicylic Acids↗
PubMed1995

Interleukin-2 receptor alpha and beta chain expression by circulating alpha beta and gamma delta T cells in inflammatory bowel disease.

The pathogenetic role of activated alpha beta and gamma delta T cells in inflammatory bowel disease (IBD) is not well defined. To elucidate this, interleukin-2 receptor (IL-2R) alpha and IL-2R beta single chain expression and coexpression by peripheral blood TCR alpha beta + cells and TCR gamma delta + cells was studied in 21 patients with ulcerative colitis (UC), 25 with Crohn's disease (CD), and 15 controls. The percentages of IL-2R alpha + beta-, IL-2R alpha-beta +, and IL-2R alpha + beta + TCR alpha beta + cells were increased in IBD patients with moderate and severe disease activity, as compared to controls (P < 0.01). In contrast, the percentages of IL-2R alpha-beta + and IL-2R alpha + beta + TCR gamma delta + cells were increased in patients with inactive UC (P < 0.01), but not in CD. The results suggest that activated alpha beta T cells are involved in the development of IBD. The differences in gamma delta T cell IL-2R expression between inactive UC and CD may correspond to a yet undefined etiopathogenetic difference between these two diseases.

Adolescent↗
PubMed1994

Direct and quantitative vitamin B12 absorption measurement in patients with disorders in the distal part of the bowel. Comparison of stool spot test [SST] with whole body counting in patients with ileal pelvic reservoir, ileostomy or Crohn's disease.

Direct and quantitative vitamin B12 absorption studies were performed in 25 patients with disorders in the distal small intestine using whole body counting as the gold standard. Simultaneously, vitamin B12 absorption was also determined by the more simple stool spot test (SST) which incorporates 51CrCl3 as a nonabsorbable marker. The SST provided a reliable direct and quantitative measure of vitamin B12 absorption in patients with previous ileal resections due to Crohn's disease (CD) (n = 7) as compared with whole body counting. In ulcerative colitis (UC) patients with either an ileal pelvic reservoir (n = 10) or a conventional ileostomy (n = 8), markedly shorter bowel transit times and absence of colon may have hindered sufficient mixture of the tracer and marker isotopes which could explain the false absorption values according to the SST in single patients. Therefore, an intact colon and a near-normal bowel transit time seem to be essential for performance of the SST. Whole body counting showed, as expected, that all CD patients except one had decreased vitamin B12 absorption (median 23%; range 3-39%) (normally > 35%). In UC patients with ileostomy, only one had a markedly decreased vitamin B12 absorption, two borderline normal values, while the rest had normal values (median 54%, range 15-76%). All UC patients with ileal pelvic reservoir had normal vitamin B12 absorption values (median 40.5%, range 36-87%). We conclude that vitamin B12 substitution therapy is probably required in patients with CD with ileal resection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in active inflammatory bowel disease.

Intercellular adhesion molecule (ICAM)-1 promotes the initial interaction between macrophages and T cells during immune activation. We have measured serum levels of soluble ICAM-1 (sICAM-1) by ELISA in 27 patients with ulcerative colitis (UC), 31 with Crohn's disease (CD), and 29 healthy subjects. The median sICAM-1 serum concentration was significantly increased in inflammatory bowel disease (IBD) patients (355 ng/ml, range 195-855) compared to controls (245 ng/ml, 155-580) (P = 0.001). Variance analysis for trend showed that sICAM-1 levels were significantly higher in patients with active CD and UC, compared to those with inactive disease and controls (P = 0.00002). The concentration of sICAM-1 was higher in CD patients (365 ng/ml 230-470) compared to UC (300 ng/ml 195-855) (P = 0.01). Furthermore, weak but significant correlations were found between serum levels of sICAM-1 and: soluble IL-2 receptors, orosomucoid, and C-reactive protein. It is suggested that increased circulating sICAM-1 levels may reflect increased adhesiveness and signal transmission across cells, probably as a result of shedding of the parent molecule during local cellular immunoresponses in vivo.

Acute-Phase Proteins↗
PubMed1993

Circulating and mucosal concentrations of tumour necrosis factor and inhibitor(s) in chronic inflammatory bowel disease.

Monokines, in particular the interleukin-1 family and tumour necrosis factor alpha, have been implicated in the pathogenesis of chronic inflammatory bowel disease. We initially assessed the circulating levels of tumour necrosis factor alpha by ELISA in 20 patients with active Crohn's disease, ten patients with active ulcerative colitis, and ten healthy volunteers. Circulating levels of tumour necrosis factor alpha did not differ significantly between patients (median 80 pg/ml, range 0-2.375) and healthy volunteers (median of 0 pg/ml, range 0-780) (p = 0.16). If a limit of 40 pg/ml was applied, 21 of 30 patients had abnormal values compared to three out of ten controls (p = 0.06), and for the subgroup of patients with Crohn's disease, there was a significantly higher number of abnormal values as compared to controls (p < 0.05), whereas no such difference was found for ulcerative colitis. A parallel study of ten Crohn's disease patients suggested that this result was not explained by differences in circulating tumour necrosis factor alpha inhibitor levels of tumour necrosis factor alpha were measured in 31 patients with active chronic inflammatory bowel disease, 16 with Crohn's disease and 15 with ulcerative colitis. Very low mucosal tumour necrosis factor alpha values were detected in only three patients. Taken together, these results suggest that increased production of tumour necrosis factor does not play a major role in the pathogenesis of chronic inflammatory bowel disease.

Adolescent↗
PubMed1992

Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin.

Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.

Adolescent↗
PubMed1992

Increased concentrations of interleukin 1 beta, interleukin-2, and soluble interleukin-2 receptors in endoscopical mucosal biopsy specimens with active inflammatory bowel disease.

Concentrations of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), and soluble IL-2 receptors (sIL-2R) were determined by enzyme linked immunosorbent assays (ELISA) in supernatants of sonicated endoscopical mucosal biopsy specimens from 31 patients with inflammatory bowel disease and 19 controls. IL-1 beta was detected in 53% of the patient supernatants (p = 0.0001), IL-2 in 35% (p = 0.0031), compared with none of the controls. Soluble IL-2R was present in 55% and 26% of the specimens, respectively (p = 0.07). The concentrations of IL-1 beta (p = 0.00015), IL-2 (p = 0.0019), and sIL-2R (p = 0.0073) were highest in the most inflamed biopsy specimens, compared with less inflamed specimens and controls. There were no significant differences in IL-1 beta, IL-2, and sIL-2R concentrations between ulcerative colitis (16) and Crohn's disease patients (15). The results suggest that enhanced cellular immunity operates in vivo at the mucosal level in active inflammatory bowel disease.

Aged↗
PubMed1992

Cyclosporin pharmacokinetics after intravenous and oral administration in patients with Crohn's disease.

Cyclosporin kinetics were estimated after single-dose intravenous and oral administration in 12 patients with Crohn's disease in accordance with a three-compartment model with zero-order inputs. Cyclosporin was measured in whole blood with a specific monoclonal radioimmunoassay. The median bioavailability (f) was 23.7% (range, 0-49.1%); the distribution volume at steady state, 2.3 l/kg (range, 1.0-3.5 l/kg); clearance (CL), 7.6 ml/min/kg (range, 4.8-10.8 ml/min/kg); and t1/2(z) 7.9 h (range, 3.2-13.9 h). Both the extent and rate of bioavailability were significantly lower in six of the patients, who had low or undetectable cyclosporin levels during a preceding therapeutic trial. After repeated oral administration significant correlations were found between the single-dose f/CL ratios and the steady-state blood concentrations, indicating that the kinetics did not change markedly with time. We conclude that the disposition kinetics of cyclosporin in patients with Crohn's disease are comparable to those of other groups, whereas the bioavailability may be decreased. It is suggested that cyclosporin levels should be monitored closely, and intravenous treatment should be considered in patients with a rapid gut transit time, because cyclosporin absorption seems to follow zero-order kinetics.

Administration, Oral↗
PubMed1991

Inhibitor of interleukin-1 alpha and interleukin-1 beta-induced T-cell activation in serum of patients with active Crohn's disease.

Interleukin-1 is a family of polypeptides with a wide spectrum of immunoinflammatory activities pertinent to Crohn's disease, including T-cell activation. Using specific enzyme-linked immunosorbent assays, only sera from two of 19 patients (11%) with active Crohn's disease contained interleukin-1 alpha and interleukin-1 beta activity. Using the thymocyte proliferation assay, sera from the same patients contained significantly increased inhibitory activity against interleukin-1 alpha (P = 0.025) and interleukin-1 beta-induced cell activation (P = 0.00005) as compared with controls. Changes in both interleukin-1 alpha (P = 0.020) and interleukin-1 beta (P = 0.012) inhibitor concentrations correlated significantly with changes in clinical disease activity. None of the patient sera contained IgG or IgM autoantibodies to IL-1 alpha, nor did they exert significant inhibitory activity against interleukin 1 beta in the fibroblast prostaglandin E2-induction assay. Taken together, these data provide evidence for the presence of one or several regulators of interleukin-1-induced T-cell activation in sera from patients with active Crohn's disease.

Adult↗
PubMed1991

Interleukin-2 stimulation of blood mononuclear cells from patients with inflammatory bowel disease.

The functional capacity of biologically active, high-affinity interleukin-2 receptors (IL-2R) was studied by means of interleukin-2 (IL-2) stimulation of blood mononuclear cells (BMC) from 22 patients with inflammatory bowel disease (IBD) and 24 controls. The spontaneous, as well as the IL-2-induced, proliferative responses were significantly decreased in patients with active IBD, whereas the expressions of biologically inactive, low-affinity IL-2R (i.e. TAC antigen or CD25) were significantly increased in the same BMC cultures. In contrast, no significant differences were seen between patients and controls when BMC were stimulated with a nonspecific mitogen (phytohemagglutinin). The results suggest that a downregulation of IL-2 responsiveness may contribute to decreased BMC proliferation in vitro in active IBD.

Adolescent↗
PubMed1991

Final report on a placebo-controlled, double-blind, randomized, multicentre trial of cyclosporin treatment in active chronic Crohn's disease.

In a previous report we published the immediate results of a 3-month placebo-controlled trial (n = 34) showing that cyclosporin (n = 37) has a beneficial therapeutic effect in active chronic Crohn's disease. Here we report on the final outcome of the patients. During the 3-month tapering-off period eight initially improved patients (36%) in the cyclosporin group worsened, as did six (55%) in the placebo group. The therapeutic gain of cyclosporin treatment was consistently significant during this period. It ranged from 22% to 25% (95% confidence limits, 2-46%). An outcome ranking showed that 7 patients of the cyclosporin group (19%) were substantially improved, 7 (19%) moderately improved, and 23 (62%) not improved after the tapering off. In contrast, no significant differences were seen during the 6-month follow-up period. Four patients of the cyclosporin group (11%) were substantially improved, 3 (8%) moderately improved, and 30 (81%) not improved at final follow-up. Significant interactions between cyclosporin and prednisolone treatment were demonstrated both at the end of the initial treatment period and at the end of the tapering-off period. We conclude that a short course of cyclosporin treatment does not result in long-term improvement in active chronic Crohn's disease.

Chi-Square Distribution↗