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A Tromm

Publications and source records attributed to A Tromm.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mechanism-based PK/PD model for the lymphocytopenia induced by endogenous and exogenous corticosteroids.

OBJECTIVE: Lymphocytopenia is a sensitive surrogate marker for the immunological effects of corticosteroids. This pharmacokinetic/pharmacodynamic (PK/PD) study investigated whether the circadian variation of blood lymphocytes observed after placebo is secondary to the circadian rhythm of endogenous cortisol, and developed based on this relationship an improved PK/PD model for a more sensitive description of the effect of low-dose corticosteroid therapy on blood lymphocytes considering the net activity of the exogenous corticosteroid budesonide and endogenous cortisol. METHODS: In an open, parallel study design, 3 mg oral budesonide or placebo were given at 8.00 a.m., 4.00 p.m. and midnight to two groups of 12 volunteers. Lymphocyte counts and serum concentrations of budesonide and cortisol were monitored for 24 hours. A mechanism-based PK/PD model which considered the non-linear protein binding of cortisol and the budesonide-induced cortisol suppression was employed to relate changes in blood lymphocytes to free cortisol levels after placebo and to the net activity of free budesonide and free endogenous cortisol after active treatment. RESULTS: The circadian rhythm of blood lymphocytes observed after placebo could inversely be related to the circadian rhythm of serum cortisol. After budesonide administration, lymphocyte counts could accurately be linked to the net activity of budesonide and endogenous cortisol. The resulting EC50 values for the effect of budesonide on cortisol, budesonide on lymphocytes and cortisol on lymphocytes were 0.063 +/- 0.034, 0.22 +/- 0.13 and 26.3 +/- 15.0 ng/ml (placebo group 15.4 +/- 3.4 ng/ml), respectively. CONCLUSIONS: The presented mechanism-based PK/PD model suggests that blood lymphocytes are under physiological control of cortisol. It further indicates that endogenous and exogenous corticosteroids and their pharmacological interaction need to be considered for modeling the effects of low doses of exogenous corticosteroids on the immune system.

Anti-Inflammatory Agents↗
PubMed1998

[Optimizing antrum planimetry for ultrasound determination of gastric emptying using emptying function reference lines].

UNLABELLED: Previous studies have shown high inter- and intraindividual variation coefficients (Vkinter; Vkintra) of the gastric emptying time t(end) determined by sonographical antrum planimetry. PURPOSE: Are there new parameters reflecting the functional process of gastric emptying? METHOD: Gastric emptying of 300 ml water was studied in 20 healthy volunteers by sonographical antrum planimetry. 10 volunteers were examined a second time on another day. RESULTS: High variation coefficients Vkinter (42%) and Vkintra (31%) could be demonstrated. Moreover, a correlation of r = +0.922 between tend and the maximal percentual increase of the antral area was evident. This relation is introduced as the functional-emptying-line (FEL). CONCLUSION: Using the functional aspects of FEL, gastric emptying can be studied sonographically under functional aspects.

Adult↗
PubMed1998

Increased serum levels of vascular endothelial growth factor in patients with inflammatory bowel disease.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic, vascular permeability-enhancing, and calcium-dependent enzyme-modulating cytokine with overexpression in various pathologic disorders, including granulomatous inflammation, tissue repair, delayed hypersensitivity reactions, rheumatoid arthritis, and tissue ischemia. The present study investigates the role of VEGF in chronic inflammatory bowel disease. METHODS: Thirty-one patients with Crohn's disease, 15 patients with ulcerative colitis, and 9 healthy volunteers were studied. VEGF serum levels were measured with a solid-phase enzyme-linked immunosorbent assay. RESULTS: Significantly increased VEGF serum levels were observed in both active Crohn's disease and active ulcerative colitis when compared with healthy controls. Patients with active Crohn's disease and active ulcerative colitis showed significantly higher VEGF serum levels than patients with quiescent disease. No difference was observed between inactive disease and healthy controls. In addition, strongly increased VEGF serum levels were found in patients with Crohn's disease with fistulas in the absence of clinical, endoscopic, histologic, and laboratory findings of disease activity. CONCLUSIONS: Significantly increased VEGF serum levels were observed in patients with active Crohn's disease and ulcerative colitis, which suggests that VEGF has an important role in chronic inflammatory bowel disease. Its possible association with fistulas has yet to be determined.

Adult↗
PubMed1998

[Jaundice and progressive liver failure: delayed diagnosis of autoimmune hepatitis due to abrupt termination of steroid therapy?].

A 27-year-old woman was successfully treated with a highly dosed steroid therapy over several months during summer 1994 in the event of urticaria. In October 1994, when the patient was complaint free, therapy was abruptly terminated. In November 1994 jaundice, nausea and loss of appetite occurred. Biochemical results showed markedly elevated serum transaminases, negative hepatitis serology, normal immunoglobulins and inconspicious autoantibodies. Histology showed a florid hepatitis. In January 1995 the patient was hospitalized again in very low general and nutritional condition with a marked jaundice, high serum transaminases, insufficient liver synthesis function, established ANA(+), ASMA(+2) and normal immunoglobulins. This time histology painted out an active hepatitis going into liver cirrhosis. Evaluation in view of liver transplantation was carried out in this case of liver failure. At that time, tests showed a distinct gamma globulin fraction increase although the antibody pattern had remainded identical. An immunosuppressive therapy with azathioprine and steroids was decided upon under suspicion of an autoimmune hepatitis leading to a prompt positive response and therefore confirmation of the diagnosis. Complete biochemical remission was attained in April 1995 and a complete histological remission in March 1998.

Adrenal Cortex Hormones↗
PubMed1997

[Bronchopulmonary manifestations of gastroenterologic and hepatic diseases].

Topics of this review are the bronchopulmonary manifestations of gastroesophageal reflux disease, cirrhosis of the liver and chronic inflammatory bowel diseases. About 20% of patients with chronic obstructive airway disease show evidence of gastroesophageal reflux disease. Reflux bronchoconstriction seems to be of greater importance than microaspiration. First studies show the positive effects of acid inhibition by proton pump inhibitors on pulmonary symptoms. Hepatorenal syndrome is characterized by arterial hypoxemia with PaO2-values < 70 mm Hg. Different mediators (endotoxins, amines, polypeptides or allergens) are discussed. Furthermore, elevated levels of prostacycline, atrial natriuretic factor and platelet activating factor have been described. Recently published studies focused on the role of nitric oxide (NO). Patients with cirrhosis of the liver show a higher rate of a pathologically elevated airway resistance which might be induced by a reduced histamine clearance. Ascites leads to reversible restrictive airway disease. Bronchopulmonary manifestations in chronic inflammatory bowel diseases include obstructive and restrictive airway diseases, vascular or serosal changes and show low clinical evidence. In contrast, pathological changes of the common function tests were found in 30 to 50%. These findings may be induced by circulating immune complexes, vasculitis, increased permeability or a combined immune reaction of both, the bronchial and intestinal mucosa. Undesired effects of salicylates should be taken into account. This review shows that bronchopulmonary manifestations in diseases of the Gl-tract or the liver are more common than usually known and should be taken into clinical consideration.

Gastroesophageal Reflux↗
PubMed1996

Oral pH-modified release budesonide versus 6-methylprednisolone in active Crohn's disease. German/Austrian Budesonide Study Group.

OBJECTIVE: Corticosteroids are effective in acute Crohn's disease (CD). The present study assessed the effectiveness and safety of oral pH-modified release budesonide (BUD) in patients with active CD in comparison with 6-methylprednisolone (MPred). DESIGN: This was a prospective multicentre, randomized, double-blind, double-dummy study. METHODS: A total of 67 patients with active CD (CDAI > 150) were included. Patients were treated with 3 x 3 mg BUD (n = 34) or MPred (n = 33) according to a weekly tapering schedule (48-32-24-20-16-12-8 mg). The primary aim was remission of CD (CDAI < 150 and decrease by at least 60 points from baseline) after eight weeks. RESULTS: Baseline demographics, disease activity and localization of CD in the small bowel and the colon were similar in both treatment groups. On an intention-to-treat basis 19/34 patients in the BUD group (55.9%) and 24/33 patients in the MPred group (72.7%) were in remission after eight weeks (P = 0.237). Therapy failed in 15/34 patients (44.1%) of the BUD group and in 9/33 patients (27.3%) of the MPred group. The mean CDAI decreased from 262 +/- 50 to 118 +/- 69 in the BUD-group and from 262 +/- 81 to 95 +/- 61 in the Mored group (P = 0.183, final CDAI BUD vs. MPred). Steroid-related side effects appeared in 28.6% of the patients in the BUD group and in 69.7% of the patients in the Mored group (P = 0.0015). CONCLUSIONS: Oral pH-modified release budesonide (3 x 3 mg/day) is almost as effective as a conventional corticosteroid in patients with active CD but causes significantly less corticosteroid-related side effects.

Administration, Oral↗
PubMed1995

Enhanced superoxide anion release of normal neutrophil granulocytes primed with sera of patients with inactive inflammatory bowel disease.

During active inflammatory bowel disease (IBD) the respiratory burst of neutrophil granulocytes has been shown to be impaired using isolated circulating neutrophil granulocytes of patients with active disease. Using normal neutrophil granulocytes of healthy volunteers the present study examines the potential priming effect of sera of patients with active and quiescent IBD. The superoxide anion (O2-)-release of normal neutrophil granulocytes in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) has been investigated after incubation with sera of patients with active and inactive Crohn's disease and ulcerative colitis. O2(-)-release was measured using the superoxide dismutase inhibitable reduction of ferricytochrome c. The O2(-)-release of normal neutrophil granulocytes primed with sera of patients with inactive Crohn's disease (607.1 +/- 218.2 nmol/60 min, n = 10, p = 0.001) or cultured with sera of patients with quiescent ulcerative colitis (497.4 +/- 94.9 nmol/60 min, n = 3, p = 0.005) was significantly enhanced when compared with sera of normal controls (319.8 +/- 86.5 nmol/60 min, n = 10). There was no significant difference between priming with sera of patients with quiescent or active Crohn's disease (481.0 +/- 113.0 nmol/60 min, n = 5). Normal neutrophil granulocytes primed with sera of patients with active ulcerative colitis produce significantly larger amounts of O2- (809.5 +/- 256.9 nmol/60 min, n = 4, p = 0.001) when compared with sera of normal controls. The study shows that sera of patients with quiescent IBD as well as sera of patients with active disease have the potential to prime normal neutrophil granulocytes for an enhanced O2(-)-release in response to FMLP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

[Rheumatoid disorders in Crohn disease and ulcerative colitis. Dominance of non-inflammatory factors].

82 consecutive outpatients with Crohn's disease (n = 52) and ulcerative colitis (n = 30) were examined ambulatory. Rheumatic complaints, objective results and diagnosis were correlated to the activity of the underlying illness and the extent of the bowel affected. 61% of the examined patients complaint about rheumatic pains. In two thirds this could be attributed to noninflammatory causes (30% insertion tendinitis. 16% degenerative arthritis, 16% wrong carriage), which appeared to be independent of the activity and severity of the underlying disease. One fourth of the rheumatic complaints was caused by inflammation (21% arthritis, 5% sacroileitis). In these cases a dependency on the disease activity and the extent of the colon involvement could be found. No cause was found for 12% of the rheumatic complaints. In patients with ulcerative colitis suffering from arthritis a significant increase of disease activity (Rachmilewitz index) could be shown as compared to ulcerative colitis patients without arthritis (p < 0.02). For patients with Crohn's disease no significant correlation between arthritis and disease activity could be established. In these cases the occurrence of arthritis was associated with the colon involvement (Chi2 = 8.48). The data indicate the high frequency of rheumatic complaints in inflammatory bowel diseases due to noninflammatory causes.

Adolescent↗
PubMed1994

[Osteopenia in chronic inflammatory bowel diseases. Results of a cross-sectional study using quantitative computerized tomography].

53 unselected patients with Crohn's disease (CD) (35 female, 18 men; mean age: 32.3 +/- 12.5 y.; mean duration of CD: 78.6 +/- 65.7 months) and 23 patients with ulcerative colitis (UC) (8 female, 15 men; mean age: 43.7 +/- 17.9 y.; mean duration of UC: 100.7 +/- 86.0 months) were examined by quantitative computertomography (lumbar spine 1-3). Incipient (manifest) osteopenia (OP) was defined as a reduced axial bone mineral density from -1 standard deviations (SD) to -2 (SD) (< -2SD) as compared to a control Group. Reduced bone mineral density was found in 30.2% (16/53) of patients with CD and 9% (2/23) with UC (p < 0.05). In particular 12/53 pts. (22.6%) with CD and 1/23 pts. (4.35%) with UC showed incipient OP, whereas 4/53 pts. (7.5%) with CD and 1/23 pts. (4.35%) with UC showed manifest OP. With respect to the location of CD the mean relative bone density (SD) was found to be significantly lower in patients with ileal involvement of CD (-0.88 +/- 0.8 SD; n = 39) as compared to patients with colonic involvement (-0.09 +/- 0.86 SD; n = 14) and UC (-0.09 +/- 0.55 SD; n = 23) (p < 0.05). No significant correlation to the duration of the disease was found. Previous therapy with steroids led to lower mineral bone density as compared to untreated patients. As a trend duration of steroid treatment and bone density were shown to be correlated inversely.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1993

[Acute effect of metoclopramide on esophagus motility in diabetes mellitus].

The acute effect of metoclopramide on oesophageal motility was investigated prospectively in 33 consecutive patients (20 men and 13 women; mean age 60.5 +/- 12.6 years) with type I (n = 8) or type II (n = 25) diabetes. 15 patients had a peripheral sensory-motor polyneuropathy only and three just an autonomic cardial neuropathy. Both lesions were present in ten, none in five. No patient had oesophago-gastroduodenal lesions. Sphincter pressure, relaxation time, contraction amplitude and propulsion velocity of bolus-induced oesophageal peristalsis were measured manometrically after intravenous administration of 10 mg metoclopramide. Resting pressure in the lower oesophageal sphincter rose significantly by 26.7%, contraction amplitude in the tubular portion of the oesophagus by more than 30%, and propulsion velocity by more than 20% (P for each < 0.05). At the same time the amount of segmental and aperistaltic oesophageal contractions regressed significantly. The effect of metoclopramide was demonstrated regardless of the type of diabetes, duration of diabetes and any manifestation of autonomic cardial or peripheral sensory-motor neuropathy.

Adult↗
PubMed1993

[The long-term effect of molsidomine on frequency of hemorrhage, portal and cardiac hemodynamics in patients with liver cirrhosis--a pilot study].

The aim of the study was to examine the effects of maintenance molsidomine therapy on portal and cardiac haemodynamics in patients with confirmed alcoholic or nonalcoholic liver cirrhosis and portal hypertension. Molsidomine is a selective reducer of preload without development of tolerance. 16 patients with portally decompensated cirrhosis of the liver following an initial or recurrent episode of bleeding form oesophageal/fundal varices were on long-term treatment (4-24 months) with 2 or 3 x 8 mg molsidomine/day (Corvaton retard). They were followed up after 3-6 months. 6 of the 16 had been treated previously with propranolol for haemorrhage prophylaxis over 11 +/- 15 months. In a total of 70 treatment months with propranolol, 10 recurrent bleeds had occurred. During 166 treatment months with propranolol, 10 recurrent bleeds had occurrences of bleeding. This long-term treatment showed reductions in hepatic venous pressure gradient of 24.8% (n = 8) (p < 0.05), variceal pressure of 28.7% (n = 7) (p < 0.05) and size of varices of 17% (n = 8). This occurred without any clinically relevant impairment of systemic cardiovascular regulation. Therefore long-term therapy with molsidomine may be suitable for prophylaxis of haemorrhage of oesophageal varices.

Adult↗
PubMed1992

[Lactose intolerance in chronic inflammatory bowel diseases].

In 124 patients with Crohn's disease (69 women, 55 men; mean age 33.7 [11-66] years) and 53 with ulcerative colitis (30 women, 23 men; mean age 36.2 [19-74] years) the incidence of lactose intolerance, as measured by the H2 breath test and blood sugar concentration, was determined prospectively. To exclude abnormal bacterial colonization of the small intestine or rapid small-intestine transit after partial resection of the small intestine as a cause of lactose intolerance, the oro-caecal transit time for lactulose (H2 breath test) was measured. While 21 of 124 patients with Crohn's disease (16.9%) had the expected incidence of lactose intolerance, this was present in only 2 of 53 patients with ulcerative colitis (3.8%; P < 0.05). The lactose intolerance was independent of the site of any inflammatory changes, disease activity and extent of small-intestine resection. Oro-caecal transit time for lactose was similar for all patients. There was no lactose intolerance in two patients with abnormal small-intestinal bacterial colonization.--Because of their considerable diagnostic and prognostic significance, tests for lactose intolerance should be performed routinely in all cases of Crohn's disease or ulcerative colitis.

Adolescent↗
PubMed1992

[Value of alpha-1-antitrypsin and thrombocytes in the assessment of inflammatory activity in Crohn disease].

In 40 patients with Crohn's disease the subsequent parameters were determined in relation to the endoscopic features (group A: no or slight activity respectively [n = 26]; group B: severe inflammation of the mucosa [n = 14]; group C: patients of group B after four-weeks treatment): Crohn's disease activity index (CDAI), van Hees activity index (VHAI), C-reactive protein (CRP), ESR (erythrocytic sedimentation rate), albumin, hematocrit, platelets, alpha-1-antitrypsin (A1AT), antithrombin III, fibrinogen, clotting factors V and VIII. The hemostaseological tests were compared to the data of 16 healthy controls. The results showed significant differences regarding the mean values of CRP, ESR, albumin, CDAI, VHAI, platelets and A1AT between group A, B and C. No influence of localization or duration of the disease, age or sex could be shown by multivariate analysis. The highest test efficacy to discriminate between patients of group A and B was determined for VHAI (81.1%) and alpha-1-antitrypsin (78.4%). CDAI, platelet count, ESR (each 75.7%), CRP (70.3%) and hematocrit were less efficient. Levels of fibrinogen (59.4%) and clotting factors V (59.4%) and VIII (64.8%) were much less important. In conclusion A1AT and platelet count should be regarded as helpful tests in the evaluation of the inflammatory activity in Crohn's disease.

Adolescent↗
PubMed1992

Acute pancreatitis complicating Crohn's disease: mere coincidence or causality?

An example of acute pancreatitis developing five weeks after initial treatment with 5-aminosalicylic acid (5-ASA) and methylprednisolone for severe Crohn's disease is reported in a 37 year old female patient. She had undergone cholecystectomy for gall stones some years earlier. There was no evidence of acute or chronic pancreatitis. No morphological changes of the upper gastrointestinal tract were found except for some irregularity of the main pancreatic duct and the secondary ducts on endoscopic retrograde pancreatography. Rechallenge with 5-ASA did not induce recurrent pancreatitis or changes in pancreatic enzymes. This case report supports the concept of an association between acute pancreatitis and Crohn's disease.

Adult↗
PubMed1992

Evaluation of different laboratory tests and activity indices reflecting the inflammatory activity of Crohn's disease.

In a prospective study we compared the usefulness of various laboratory tests (albumin, alpha-1-proteinase inhibitor (A1PI), cholinesterase (CHE), C-reactive protein, erythrocyte sedimentation rate, hematocrit) and activity indices (CDAI, VHAI) in relation to the disease activity by endoscopic criteria. Except for hematocrit highly significant differences (p less than 0.0005) of the mean values of all test results were found for patients without or with slight mucosal lesions compared with patients with severe inflammation of the mucosa. Further analysis of the data indicates the highest test efficiency (84%), sensitivity (80%), and specificity (88.6%) for CHE. CHE showed good correlations to all other tests; the highest correlation was found between CHE and VHAI (r = -0.78). We suggest that a suppression of CHE synthesis mediated by endotoxins and cytokines rather than an increased intestinal loss explains the decreased CHE in severe Crohn's disease. It is concluded from the data that CHE is a useful test to assess the inflammatory activity of Crohn's disease.

Adolescent↗