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J Kjeldsen

Publications and source records attributed to J Kjeldsen.

At least 19 recordsLinked to original sources
PubMed2004

Prediction of therapy in primary endoscopic retrograde cholangiopancreatography.

BACKGROUND AND STUDY AIMS: It seems rational to perform endoscopic retrograde cholangiopancreatography (ERCP) if the probability of endoscopic therapy is high, but to carry out magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) first if this probability is moderate or low. The aim of the present study was to develop a model describing the probability of endoscopic therapy in patients without previous biliary imaging. PATIENTS AND METHODS: The development of the model was based on stepwise multiple logistic regression applied to 2470 prospectively registered first-time ERCP procedures. The model was evaluated by application to 442 prospectively registered first-time ERCP procedures entered in the database in the following 2 years. RESULTS: Predictors selected were: age, gender, p-amylase >/= 400 U/l, ln(s-bilirubin), ln(s-alkaline phosphatase), common bile duct (CBD) stone seen on transabdominal ultrasonography, gallbladder stone seen on transabdominal ultrasonography, interaction of dilated bile ducts seen on transabdominal ultrasonography with ln(s-bilirubin), and interaction between age and male gender. The area under the receiver operating characteristic (ROC) curve was 0.875 and there was good fit of the model. A test with a probability cutoff value of 80 % had a positive predictive value (PPV) of 92.8 %. Specificity was 87.1 % and, using this test, 52.4 % of patients would have been selected for primary ERCP. In the application cohort, the frequency of therapy was higher than in the development cohort. The area under the ROC curve was 78.7 %. When used in the evaluation cohort, with a cutoff probability of 80 %, the test had sensitivity 84.0 %, specificity 49.5 %, negative predictive value (NPV) 46.6 % and PPV 85.6 %. Of the patients, 76.7 % would have been selected for ERCP. This would have identified 85.5 % of individuals needing therapeutic ERCP without use first of MRCP or EUS. Test-positive cases constituted 90.3 % of stent insertions and 86.3 % of stone extractions. CONCLUSIONS: The model is useful for selection of patients for ERCP at our center.

Adolescent↗
PubMed2003

Incomplete remission with short-term prednisolone treatment in collagenous colitis: a randomized study.

BACKGROUND: Microscopic colitis is a disease of unknown aetiology characterized by chronic watery diarrhoea and diarrhoea can be eliminated by budesonide but frequently recurs when budesonide is stopped. We studied whether prednisolone could induce remission in patients with disabling, chronic diarrhoea due to microscopic colitis. METHODS: A double-blind, randomized (3:1) trial of oral prednisolone 50 mg daily or placebo for 2 weeks. Remission was defined as stool weight < or = 200 g/day or frequency < or = 2/day; effect was defined as > 50% reduction of either stool frequency or weight. Six centres screened 31 consecutive patients and included 11 with collagenous colitis and 1 with lymphocytic colitis. Median duration of diarrhoea was 9 months. Patients had a normal colonoscopy, and no evidence of coeliac disease, bile acid or lactose malabsorption. Patients with gastrointestinal infection, previous gastrointestinal surgery, abnormal biochemical screening or recent treatment with immunosuppressive agents were excluded. RESULTS: Stool weight (grams) declined in 7 of 9 patients given prednisolone and in 1 of 3 receiving placebo; changes in median weight were from 430 to 278 and from 825 to 489, respectively. Stool frequency (per day) declined from 6 to 3 and from 8 to 5. Remission was obtained in 2 and 0, and effect in 5 and 0, respectively (NS; Fisher exact test). CONCLUSIONS: Prednisolone 50 mg daily for 2 weeks induces incomplete remission in patients with chronic diarrhoea due to collagenous colitis.

Adult↗
PubMed2003

Pharmacological monitoring of azathioprine therapy.

BACKGROUND: Studies on azathioprine (Aza) treatment in Crohn disease have indicated a positive correlation between clinical remission and a concentration in erythrocytes of the metabolites 6-thioguanine nucleotides (E-6-TGN) above 230 pmol/8 x 10(8) RBC. A concentration of the methylated Aza metabolites (E-6-MMP) above 5000 pmol/8 x 10(8) RBC has been correlated to hepatotoxicity. Thiopurine methyltransferase (TPMT) is responsible for the formation of methylated metabolites and lower E-TGN levels, and TPMT genotyping has been proposed as guidance for dosage. In a cross-sectional study we investigated relationships between the clinical outcome and Aza dose, the TPMT genotype and the Aza metabolite levels among patients with Crohn disease. METHODS: TPMT genotype (PCR assay), azathioprine metabolite levels (HPLC analysis) and xanthine oxidase (XO) activity were determined once in 71 randomly selected Crohn patients on an unaltered Aza dose for at least 3 months. RESULTS: None of the doses of Aza, TPMT genotype, E-6-TGN-, E-6-MMP levels or XO activity were significantly related to disease activity (H-B score), (P = 0.18, P = 0.69, P = 0.90, P = 0.54, P = 0.29, respectively). Leucopenia and/or hepatotoxicity were not demonstrated in any patient. Four patients had a heterozygous TPMT genotype (6.1%; 95% CI: 1.68%-14.80%). The 4 TPMT heterozygous patients had higher E-6-TGN levels than did the 67 remaining patients (P = 0.008). CONCLUSIONS: To explore the applicability of TPMT genotyping, E-6-TGN and E-6-MMP levels for therapeutic drug monitoring, large prospective studies with patient entry at the start of Aza therapy are needed. Until the results of such studies are available, the dose adjustments of Aza should be guided primarily by clinical response and blood counts; metabolite level measurements can only be applied to identify therapeutic non-compliance.

Adult↗
PubMed2002

Effects of topical ropivacaine on eicosanoids and neurotransmitters in the rectum of patients with distal ulcerative colitis.

BACKGROUND: Topical administration of lidocaine has been suggested to have beneficial clinical effects in patients with active ulcerative colitis, but the mechanism of action, if any, remains obscure. As local anaesthetics may exert anti-inflammatory actions through their inhibition of nervous reflexes, we have studied the local effects of a single rectal dose of ropivacaine gel on rectal concentrations of eicosanoids and neurotransmittors in patients with relapsing ulcerative colitis. METHODS: In a randomized, double-blind, placebo-controlled study, concentrations of leukotriene B4, thromboxane B2 and prostaglandin E2 in rectal dialysates and concentrations of substance P, neurokinin A, somatostatin, vasoactive intestinal polypeptide and calcitonin gene-related peptide in rectal biopsies from 19 patients with active, distally located, ulcerative colitis were measured before and after rectal administration of a 200-mg dose of ropivacaine- or placebo-gel by use of radioimmunoassays. For comparison with normal conditions, concentrations of neuropeptides were measured in another 19 patients with relapsing ulcerative colitis and 14 controls with non-inflamed colon. RESULTS: No significant changes in concentrations of eicosanoids or neuropeptides were observed after ropivacaine or placebo administration. Baseline concentrations of all neuropeptides, except somatostatin, were significantly lower in active ulcerative colitis than in controls with non-inflamed colon. CONCLUSIONS: These findings reveal no evidence of anti-inflammatory actions by ropivacaine in active ulcerative colitis and thus provide no rationale for topical treatment with local anaesthetics.

Administration, Rectal↗
PubMed2001

[Cyclosporine treatment of patients with active ulcerative colitis refractory to high-dose glucocorticoid].

In around 30-40% of patients with acute severe ulcerative colitis the disease is refractory to treatment with high-dose glucocorticoids. Adding intravenous cyclosporine to the therapy in these patients has shown encouraging short-term results. Case notes of twenty-three acutely ill patients, who received intravenous cyclosporine during the period 1992 to 1998 due to failure of high-dose glucocorticoid (n = 20) or due to medical complications (n = 3) which made surgery difficult, were reviewed. Eight patients had their first episode of ulcerative colitis whereas 15 had relapse or chronic active disease. Cyclosporine (4 mg/kg/dag) was added to glucocorticoid treatment after a median of 11 days. Clinical remission was achieved in 13 patients (57%) after a median of nine days, of these five subsequently underwent surgery. Ten did not obtain remission and went to surgery. Approximately a third of acutely ill ulcerative colitis patients refractory to standard treatment with high-dose glucocorticoids will benefit from intravenous cyclosporine in the longer term.

Adolescent↗
PubMed2001

Collagen metabolites in the peripheral and splanchnic circulation of patients with Crohn disease.

BACKGROUND: Fragments of collagen arising during synthesis and breakdown have been suggested as markers of fibrous tissue remodelling in Crohn disease. We compared serum concentrations of the C-terminal propeptide of collagen I (PICP), the N-terminal propeptide of collagen III (PIIINP) and the C-terminal telopeptide of type I collagen (ICTP) in the splanchnic and systemic circulation in Crohn disease requiring segmental intestinal resection. METHOD: 15 consecutive patients undergoing surgery due to strictures or continuous inflammation. Male:female ratio was 6:9. Blood was drawn from a peripheral vein prior to surgery. Immediately before intestinal resection, additional samples were drawn from the antecubital vein and from a mesenteric vein draining the affected intestinal segment. PIIINP, PICP and ICTP were measured with radioimmunoassays. RESULTS: Pre-surgery S-ICTP (median 5.5 microg/L; range 3.2-17.2 microg/L) was significantly increased in peripheral blood compared with healthy controls (median 2.6 microg/L; range 0.6-5.7 microg/L), P < or = 0.05. By contrast, S-PICP (median 98 microg/L; range 62-137 microg/L) and S-PIIINP (median 2.5 microg/L; range 1.2-7.4 microg/L) were significantly lower than S-PICP (median 133 microg/L; range 66-284 microg/L) and S-PIIINP (median 3.4 microg/L; range 1.0-7.1 microg/L) in healthy controls, P < or = 0.05. During surgery. no difference in S-PICP and S-PIIINP was documented between peripheral blood and splanchnic blood. In contrast, S-ICTP was increased in splanchnic blood (median 6.2 microg/L; range 2.7-17.4) compared to peripheral blood (median 5.0 microg/L; range 3.1-13.4) (P=0.05). CONCLUSION: The present study provides further evidence that the altered intestinal collagen metabolism in Crohn disease is reflected in the local and systemic circulation.

Adult↗
PubMed2000

Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia.

OBJECTIVE: Gastrointestinal bleeding occurs in a number of patients with hereditary hemorrhagic telangiectasia (HHT) and may lead to a high transfusion need. The aim of this study was to estimate the occurrence and severity of gastrointestinal bleeding in a geographically well defined HHT population. METHODS: All HHT families in the county of Fyn, Denmark, (470,000 population) have been identified. Probands and their first degree relatives, and all descendants from probands for whom one parent had HHT were eligible for inclusion in the study. A total of 77 patients with HHT were identified; of these, 76 patients (mean age: 52 yr) were evaluated and interviewed with regard to gastrointestinal bleeding, that is, a history of either hematemesis or melena. Patients charts were reviewed. RESULTS: A total of 25 HHT patients (33%) had a history of either hematemesis or melena. Of these, 12 (48%) had received blood transfusions. Seven patients had severe bleeding (that is, > or =6 units of blood within 6 months before inclusion in the study). Endoscopy had been performed in 16 of the 25 (64%) patients. Telangiectatic lesions were documented in nine at upper endoscopy and in one at sigmoidoscopy. Telangiectatic lesions were observed in all patients with severe bleeding, but in two patients epistaxis is likely to have contributed to the anemia. Among 51 HHT patients without a history of gastrointestinal bleeding, only five (10%) had previously received blood transfusions; however, none fulfilled the definition of severe bleeding. In the HHT population 29 patients were > or =60 yr old, but all patients with severe bleeding were > or =60 yr. CONCLUSIONS: A history of gastrointestinal bleeding is common in patients with HHT (33%). This study documents that 25% of HHT patients > or =60 yr suffer from severe gastrointestinal bleeding.

Adolescent↗
PubMed1998

Markers of coagulation and fibrinolysis as measures of disease activity in inflammatory bowel disease.

BACKGROUND: Activation of coagulation and fibrinolysis occurs in patients with inflammatory bowel disease. Our aim was to study the course of a marker for activation of the coagulation cascade, prothrombin fragment 1 + 2 (F1+2), and fibrinolysis, fibrin degradation products (FbDP), in patients with ulcerative colitis and Crohn's disease before and during therapy with glucocorticoids. METHODS: Twenty-seven patients with active ulcerative colitis and 42 with active Crohn's disease treated with glucocorticoids were studied. Plasma samples were drawn before, during, and at end of therapy or at time of treatment failure. F1+2 and FbDP were measured with commercially available enzyme immunoassays. RESULTS: Mean base-line concentrations of F1+2 were significantly increased in patients with ulcerative colitis (4.77 +/- 0.50 nmol/l; P < 0.0001) and in Crohn's disease (4.66 +/- 0.59 nmol/l; P < 0.0001) compared with healthy controls (1.57 +/- 0.09 nmol/l). Mean base-line concentrations of FbDP were significantly increased in patients with ulcerative colitis (1264 +/- 161 microg FE/l; P < 0.0001) and in Crohn's disease (491 +/- 51 microg FE/l; P < 0.0001) compared with healthy controls (194 +/- 21 microg FE/l). During treatment with glucocorticoids the plasma concentrations of FbDP decreased in patients with Crohn's disease achieving remission and in patients with ulcerative colitis avoiding surgery but remained unchanged in patients not responding to therapy. In contrast, F1+2 remained increased in patients with Crohn's disease and ulcerative colitis irrespective of outcome. CONCLUSION: The present data support the concept that coagulation cascade and fibrinolysis is activated in patients with active inflammatory bowel disease. F1+2 and FbDP correlate poorly with the clinical disease activity and acute-phase reactants. The clinical response to treatment with glucocorticoids is accompanied by a decrease in plasma concentrations of FbDP but not in F1+2. FbDP may emerge as a new marker in the assessment of disease activity in patients with inflammatory bowel disease.

Adult↗
PubMed1997

[Legionella infection with rhabdomyolysis].

Rhabdomyolysis complicating infection with Legionella pneumophila has previously been reported and may in some cases have led to acute tubular interstitial necrosis. We report a case of severe Legionnaires' disease complicated with rhabdomyolysis, myoglobinuria and neurological symptoms. Treatment with erythromycin and rifampicin was initiated early in the course of disease. The myoglobinuria was treated with forced diuresis and alkanization and renal failure did not develop. The frequency of rhabdomyolysis as a complication to Legionnaires' disease is not known. In addition, the pathogenesis and possible risk factors have not yet been determined. Considering the seriousness of this complication and until further investigations have been performed we recommend that routine determinations of creatine phosphokinase are performed in the evaluation of these patients.

Adult↗
PubMed1997

Serum concentrations of orosomucoid: improved decision-making for tapering prednisolone therapy in patients with active inflammatory bowel disease?

BACKGROUND: The reliability of clinical judgment for the tapering of glucocorticoids in patients with active inflammatory bowel disease has been questioned. METHODS: The current study compared decision-making strategies on the basis of a combination of disease indices and serum concentrations of orosomucoid (strategy A) and disease indices only (strategy B) for the tapering of prednisolone. Twenty-nine patients with clinically active ulcerative colitis and 59 patients with Crohn's disease and increased concentrations of S-orosomucoid participated. The initial dose of prednisolone was 40 or 75 mg, which was tapered off over a minimum of 6 or 8 weeks. RESULTS: The tapering schedule was completed in 11 of 44 (25%) patients treated in accordance with strategy A, whereas 28 of 44 patients (64%) and prednisolone completely tapered, in accordance with strategy B. At follow-up 4 of 11 patients (36%) and 17 of 28 patients (61%) treated in accordance with strategies A and B, respectively, had clinical relapse (0.10 > P > 0.05). By means of multiple regression analysis a high serum concentration of orosomucoid and previous disease activity were identified as predictors of relapse. CONCLUSION: A therapeutic end-point of normalization of an increased level of S-orosomucoid in addition to clinical remission may be difficult to use, as serum concentrations may be continuously increased in spite of clinical remission. However, this goal may still be relevant, as a trend towards higher risk of relapse was found in patients with increased orosomucoid concentrations after completing therapy.

Adult↗
PubMed1997

Graphical interpretation of analytical data from comparison of a field method with reference method by use of difference plots.

Various viewpoints have been offered regarding the appropriate use of scatter plots or difference plots (bias plots or residual plots) in comparing analytical methods. In many of these discussions it seems the basic concepts of identity (within inherent imprecision) and acceptability based on analytical goals (analytical quality specifications) have been forgotten. With the increasing number of Reference Methods in laboratory medicine, these basic concepts are becoming more important in validation of field methods. Here we describe a simple and effective graphical test of these hypotheses (identity and acceptability) by use of difference plots. These plots display the underlying hypothesis before the measured differences are plotted and allow interpretation of the results according to specific criteria. We further describe simple but effective interpretations of the data, when the hypothesis is not fulfilled, by using two data sets drawn from comparisons of field methods for S-creatinine with a Reference Method for this analyte. The difference plot is a graphical tool with related simple statistics for comparison of a field method with a Reference Method, focusing on (a) identity within the inherent analytical imprecision or (b) acceptability within analytical quality specifications. Calculation of the standard deviation of the differences is an indispensable tool for evaluation of aberrant-sample bias (matrix effects).

Chemistry, Clinical↗
PubMed1997

Biological variation of International Normalized Ratio for prothrombin times, and consequences in monitoring oral anticoagulant therapy: computer simulation of serial measurements with goal-setting for analytical quality.

Oral anticoagulant therapy (OAT) has a well-established efficacy in prophylaxis and treatment of thromboembolic disorders. Because complications are related to intensity of OAT, optimal control of treatment is mandatory. In studies of OAT, as many as 30% of International Normalized Ratio (INR) measurements for prothrombin times fall outside the therapeutic interval. Preanalytical, analytical, and biological variation all contribute to this. Computer simulations of serial INR measurements were performed for various assumed in-treatment setpoints within the therapeutic interval INR 2.0-3.0 and for an "in-treatment within-subject variation" (CV) of 10.1%. Results are presented in difference plots with therapeutic intervals and critical differences. If the in-treatment setpoint is mid-interval (INR = 2.5), only 5% of simulated INR values fall outside the therapeutic interval. Setpoints deviating from the mid-interval and increases in the in-treatment within-subject variation considerably increase the number of observations outside the therapeutic interval and the critical differences. In conclusion, random variation, biological or analytical, and setpoints (targets) deviating from mid-interval explain a substantial number of the INR values outside therapeutic intervals observed in clinical studies. Analytical imprecision should be kept < 5% and analytical bias < +/- 0.2 INR.

Administration, Oral↗
PubMed1995

Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis.

BACKGROUND: 5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response in a number of human inflammatory diseases, such as ulcerative colitis. MK-0591 (3-(1((4-chlorophenyl)methyl)-3((1,1-dimethyl-ethyl)thio)-5(quinolin+ ++-2ylmethyl-oxy)-1H-indol-2yl)-2,2-dimethyl-propanoate) exerts its effect by binding to the 5-lipoxygenase activating protein, thereby inhibiting the translocation and activation of 5-lipoxygenase. METHODS: Concentrations of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) in rectal dialysis fluid, ex vivo biosynthesis of LTB4 in whole blood, and urinary excretion of leukotriene E4 (LTE4) from 16 patients with mild to moderately active distally located ulcerative colitis were measured by use of radioimmunoassays in a double-blind, placebo-controlled parallel-design study before and after oral administration of a 250 mg dose of MK-0591 or placebo. RESULTS: The mean LTB4 concentration in rectal dialysis fluid was lowered after MK-0591 by > 90% (p < 0.05) from 4 to 8 hours, with a maximum inhibition of 97.5% +/- 3.4% (mean +/- SD) at 20 to 24 hours after dosing, whereas PGE2 was unchanged. In whole blood, MK-0591 decreased ex vivo biosynthesis of LTB4 (p < 0.01), with a maximum inhibition of 96.4% +/- 2.1% at 4 hours after dosing. Urinary excretion of LTE4 was reduced by more than 85% (p < 0.001) from 4 to 48 hours. No adverse events were observed. CONCLUSION: These findings show that a single oral 250 mg dose of MK-0591 results in nearly complete blockade of systemic leukotriene production and LTB4 formation in the target tissue of inflammation (the rectum). Controlled multiple-dose trials to assess the clinical efficacy of this novel 5-lipoxygenase-activating protein inhibitor seem to be worthwhile.

Acute Disease↗
PubMed1995

Selective blockade of leukotriene production by a single dose of the FPL 64170XX 0.5% enema in active ulcerative colitis.

5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response of several inflammatory diseases, including ulcerative colitis. FPL 64170XX is a selective inhibitor of the enzyme 5-lipoxygenase. Concentrations of leukotriene B4 and prostaglanding E2 in rectal dialysis fluid from 23 males with clinically and sigmoidoscopically active, distally located ulcerative colitis were measured by radioimmunoassays in a double-blind, placebo-controlled, parallel design study before and after rectal administration of an enema containing 0.5% of FPL 64170XX. Repeated measures analysis of leukotriene B4, after adjusting for baseline, showed a significant treatment effect (P = 0.0014). The concentration of leukotriene B4 from rectal dialysates in patients receiving the active drug dropped to 15% (95% confidence interval 5-40%) of the placebo level in the second dialysis following administration of FPL 64170XX 0.5%. By contrast, prostaglanding E2 concentrations doubled (P = 0.0068) in patients receiving FPL 64170XX 0.5% with no change in the placebo group. These findings demonstrate that a single dose of FPL 64170XX 0.5% enema selectively blocks the generation of the 5-lipoxygenase product, leukotriene B4, to a mean of 85% in the target tissue of inflammation. Topical administration of this new leukotriene synthesis inhibitor may prove to be a clinically useful approach to the treatment of active, distally located ulcerative colitis.

Adult↗
PubMed1995

Seromarkers of collagen I and III metabolism in active Crohn's disease. Relation to disease activity and response to therapy.

Crohn's disease is characterised by gradual development of intestinal fibrotic lesions containing large amounts of collagen type I, III, and V. Measurement of circulating connective tissue metabolites has emerged as a useful tool for assessment of fibroproliferative activity in various diseases. Serum concentrations of procollagen peptides, N-terminal propeptide of type III procollagen (PII-INP), and C-terminal propeptide of type I procollagen (PICP), reflect the synthesis rate of the parent collagens, while the C-terminal telopeptide of type I collagen (ICTP) reflects its degradation. S-PIIINP, S-PICP, and S-ICTP were measured by radioimmunoassays in 29 patients with active Crohn's disease. S-ICTP was significantly increased, median 6.2 micrograms/l (95% CI 5.2 to 8.7 micrograms/l) versus controls 2.6 micrograms/l (2.5 to 2.7 micrograms/l) (p < 0.0001), S-PICP reduced, 100 micrograms/l (80 to 110 micrograms/l) versus 132 micrograms/l (124 to 141 micrograms/l) (p = 0.001), and S-PIIINP did not differ from controls. Patients with sustained clinical remission during prednisolone therapy exhibited an increase in S-PICP (p = 0.0052). S-PIIINP changed significantly (p = 0.0002), however, exhibiting a biphasic pattern. S-ICTP decreased (p = 0.015) in treatment responders but remained above the upper normal limit even when clinical remission had been achieved. Non-responders showed no significant changes in any of the marker molecules of collagen synthesis or degradation. Correlations were found between S-PIIINP and S-PICP (p < 0.005) and S-ICTP (p < 0.02), and between S-ICTP and S-orosomucoid (p < 0.005) and S-C reactive protein (p < 0.02). By contrast, there was no relation between the connective tissue metabolites and Harvey Bradshaw Index. These data provide evidence that collagen I degradation is increased not only in active Crohn's disease, but also in patients entering clinical remission. The concurrent normal/low-normal values of markers of collagen formation may reflect a changed local or systemic elimination of the propeptides.

Adolescent↗