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Biomedical subjects

W Kruis

Publications and source records attributed to W Kruis.

At least 73 records · Page 4Linked to original sources

Double-blind dose-finding study of olsalazine versus sulphasalazine as maintenance therapy for ulcerative colitis.

OBJECTIVE: To determine the therapeutic efficacy and safety of three doses of olsalazine compared with the standard dose of sulphasalazine. DESIGN: Randomized double-blind multicentre 6-month study comparing three doses of olsalazine (0.5, 1.25 and 2.0 g daily) and sulphasalazine 2.0 g daily for maintaining remission in patients with ulcerative colitis. SETTING: Public hospitals and private practices in Germany, Austria and Switzerland. PATIENTS: A total of 162 patients with ulcerative colitis in remission. RESULTS: According to intention-to-treat analysis, the failure rates of the different treatment groups were not significantly different (36, 49 and 24% for 0.5, 1.25 and 2.0 g olsalazine daily and 32% for 2.0 g sulphasalazine daily). Olsalazine and sulphasalazine showed a tendency towards lower failure rates in extended (28%) than in distal disease (44%). The withdrawal rate due to adverse effects was 4%, the most frequent single event being diarrhoea (2.5, 5.2 and 11.7% for 0.5, 1.25 and 2.0 g olsalazine daily and 0% for sulphasalazine daily). CONCLUSION: This study found no significant differences between the therapeutic efficacy or safety of 0.5-2.0 g olsalazine daily. Because of its sulpha-free formulation olsalazine may, however, be preferred to sulphasalazine.

Adolescent↗

Superoxide inhibition following different stimuli of respiratory burst and metabolism of aminosalicylates in neutrophils.

Reactive oxygen species such as superoxide radicals have been proposed to play an important role in the pathogenesis of inflammatory bowel disease. Some of the antiinflammatory actions of aminosalicylates have been ascribed to their capability to scavenge superoxide radicals directly or to inhibit its production in stimulated neutrophils. However, as a controversy still exists with regard to the precise mechanisms of inhibition and the metabolism within inflammatory cells, we compared scavenger properties of 5-aminosalicylic acid, 4-aminosalicylic acid, N-acetyl aminosalicylic acid, olsalazine, and benzalazine in systems with defined superoxide radical generation such as the dimethyl sulfoxide-NaOH and the potassium superoxide system. We also studied possible inhibition of the superoxide production following different stimuli of the respiratory burst in neutrophils and investigated the uptake and potential metabolism (N-acetylation) of 5-aminosalicylic acid in lipopolysaccharide-primed and resting neutrophils. We found that 5-aminosalicylic acid and 4-aminosalicylic acid had defined scavenger properties in the dimethyl sulfoxide-NaOH or potassium superoxide systems, respectively, whereas compounds with a modified aminophenolic structure had no effects. At the cellular level, 5-aminosalicylic acid inhibited phorbol myristate acetate (100 ng/ml)-activated superoxide generation to 82.3 +/- 9.3%, the formylmethionyl leucyl peptide (10(-5) M) to 61.0 +/- 6.8%, and the NaF (20 mM)-stimulated production to 32.3 +/- 3.2% (mean +/- SD, P < 0.01). The actions of the other drugs were less pronounced. Almost identical retention times (Rt = 11.2 min) of 3H-labeled phorbol myristate acetate in the presence and absence of 5-aminosalicylic acid revealed no in vitro interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

[A rare cause of upper gastrointestinal hemorrhage: large adenoma of Brunner's glands].

We report the rare case of a large adenoma of Brunner's glands as the cause of an upper gastrointestinal hemorrhage. Endoscopic resection is the therapy of choice in the appropriate setting. An unequivocal histological diagnosis by forceps biopsy often is not possible; there are no clear cut endoscopic criteria. The development of complications especially of severe hemorrhage increases with diameter of the adenoma. Therefore, the complete excision either endoscopically or by surgery should be attempted.

Adenomatous Polyps↗

[Recent therapeutic modalities in chronic inflammatory bowel diseases: 4- or 5-aminosalicylic acid?].

In search of new therapies in IBD, the introduction of 4-aminosalicylic acid (4-ASA) has been proposed based on the longstanding, positive clinical experience in tuberculosis, the expected similar modes of action due to the close structural analogy to 5-aminosalicylic acid (5-ASA), an established therapy in IBD, and its inexpensiveness. To better understand the mechanisms of action of aminosalicylates, the intestinal inflammatory response and to develop new, more effective and cost saving drugs it is important to compare 4-ASA with 5-ASA with respect to their pharmacology, mechanisms of action and clinical efficacy. The inhibition of the upregulation of the initial local immune response, the inhibition of the production of inflammatory mediators, e.g. leukotrienes and the direct scavenging of toxic oxygen metabolites are important common antiinflammatory mechanisms. As the clinical experience with 4-ASA is promising, but still limited, 4-ASA currently cannot yet be recommended outside clinical trials. As the costs of 4-ASA are significantly lower compared to 5-ASA, 4-ASA may replace 5-ASA in the near future provided further trials will confirm the therapeutic and pharmacologic equivalency.

Aminosalicylic Acid↗

[Endosonographic findings in the upper gastrointestinal tract in staging of malignant nodal and extranodal lymphomas].

Endoscopic ultrasound has not yet become a routine procedure for the diagnosis and therapy planning of malignant lymphomas, and it was always restricted to patients with gastric or bowel involvement. From 1990 to 1992, 33 endoscopic ultrasound investigations have been performed in 25 patients with malignant lymphomas at the Cologne University Hospital. In addition, 21 of these patients had other (conventional) diagnostic procedures at the same time serving as reference. Endoscopic ultrasound showed lymphomas in 16/21 patients, and no evidence of lymphomas in 5/21 patients. The referencial investigations together showed lymphomas in 17/21 patients, and no evidence of lymphomas in 4/21 patients. Therefore, sensitivity was 94%. 5 of the patients in addition had involvement of the upper gastrointestinal tract's wall, proven by referencial investigations, which was diagnosed correctly in all cases. The pathological lymph nodes appeared mostly as echopoor, rather sharply demarcated and homogeneous. Their size was 7 mm to 55 mm in diameter, median 11 mm. The different histological types of lymphomas could not be distinguished by means of these criteria. Endoscopic ultrasound allows a detailed view at the mediastinal and epigastrical lymph node stations and may give important informations for the staging of malignant lymphomas.

Adult↗

Effect of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase. A possible diarrhogenic factor?

Olsalazine (azodisalicylate) and mesalazine (5-aminosalicylic acid) have recently been developed as new treatment modalities for inflammatory bowel disease to avoid sulfasalazine-related side effects. However, there are reports regarding new and hitherto unexpected side effects in some patients receiving olsalazine or mesalazine, such as watery diarrhea. Since sodium pump activities play an important role in the pathogenesis of water and electrolyte disturbances, we investigated the influence of olsalazine and mesalazine on human ileal and colonic (Na+ + K+)-ATPase and its specific [3H]-ouabain binding. We found a concentration-dependent inhibition of ileal and colonic (Na+ + K+)-ATPase by olsalazine with an IC50 of 4.1 mM and 4.8 mM, respectively. Mesalazine inhibited this enzyme in the ileum with an IC50 of 4.0 mM and in the sigmoid colon with an IC50 3.5 mM. In addition, [3H]-ouabain binding was inhibited by mesalazine with an IC50 of 3.6 mM. The maximal inhibition, however, did not exceed 80% under any conditions (up to 10 mM drug concentration). Olsalazine and mesalazine induce inhibition of the ileal and colonic sodium pump activities that may (in addition to other possible mechanisms) mediate impaired water and electrolyte absorption. This is possibly of clinical relevance in patients with severely damaged mucosa. In patients with milder forms of mucosal inflammation, this inhibition most likely is of minor importance because of the great capacity of the (Na+ + K+)-ATPase and the incomplete inhibition leaving at least 20% of the enzyme activity intact.

Aminosalicylic Acids↗

Comparison between endoscopic laser and different surgical treatments for palliation of advanced rectal cancer.

The results of different treatment modalities in 196 patients with rectal carcinoma were analyzed. Patients were treated by palliative endoscopic laser therapy (n = 37), palliative surgery (n = 42), and curative surgery (n = 117). Laser therapy was successful for recanalization of the stenosis with 1.3 (range, one to five) sessions. Bleeding stopped always after a single session. If necessary, treatment was repeated monthly. Good results were seen in 35/37 patients (95 percent). They received an average of four sessions during their remaining lifetime, the median of which was eight months. No morbidity and no therapy-related mortality occurred. Palliative surgery (expanded and restricted resections) showed good results in 41/42 patients (98 percent). Morbidity was 3/42 (7 percent); mortality was 1/42 (2 percent). The median survival was 14 months for local surgical treatment and 6.3 months for deep anterior rectal resection and for abdominoperineal (Dixon's) resection. No significant difference (P = 0.15) in survival times between the palliatively treated patient groups could be detected. Survival prognosis was determined by tumor stage and outcome. In the curative (outcome R0) resection patients, morbidity and mortality were each 9/117 (8 percent). The three-year survival rate was 80 percent. If curative resection is impossible, laser therapy should be considered as an alternative to palliative surgery because of less hospitalization and seemingly less side effects. The decision on the kind of palliation in patients with rectal carcinoma should be made with regard to the patient's quality of life.

Adult↗

Cisapride increases gallbladder volume in gallstone patients before and after extracorporeal shock wave lithotripsy.

We have previously shown that oral cisapride causes a dose-related increase of fasting gallbladder volume in healthy subjects. The present study investigates the effect of cisapride on gallbladder motility in 16 patients with gallbladder stones; 8 patients had no biliary symptoms, but the other 8 patients with symptomatic gallstone disease were studied before and 6 weeks after extracorporeal shock wave lithotripsy (ESWL). For each study the patients received a single oral dose of 20 mg cisapride; fasting gallbladder volume was measured by ultrasound before, and for 120 minutes after, drug administration. In the 8 asymptomatic patients a mean maximal increase of the fasting volume to 152.7 +/- 7.6% of the initial value was observed at a mean 97.5 +/- 8.3 minutes after cisapride ingestion. Similarly, in the 8 patients with biliary pain mean fasting volume after cisapride ingestion increased to 141.3 +/- 5.7% before ESWL treatment and to 145.0 +/- 5.8% after ESWL and 6 weeks of oral litholytic therapy. There were no significant differences between the results in the symptomatic and asymptomatic patients. Our results indicate that cisapride increases the gallbladder volume in gallstone patients regardless of biliary symptoms. Similar volume changes were observed before therapy and after ESWL with bile acid therapy. The therapeutic efficacy of litholytic agents could be diminished by simultaneous cisapride administration.

Administration, Oral↗

Combined treatment of large and calcified gallstones by ESWL and laparoscopic cholecystectomy.

In order to facilitate laparoscopic cholecystectomy in the presence of large gallbladder stones seven patients underwent ESWL before operation. In six cases (83%) a fragmentation to less than or equal to 1 cm could be achieved by application of 1,605 to 2,900 (mean 2,266) shock waves with the spark-gap lithotripter Philips-Dornier MFL 5000. In these cases intraoperative stone destruction or an increase of the puncture incision size could be avoided, thus proving the efficacy of this combined treatment approach. Laparoscopic inspection was performed 2 to 48 hours after ESWL. Including two additional cases operated because of unsuccessful ESWL, hematomas of the liver and adjacent organs were observed in six of nine patients (67%). This high rate of subclinical tissue lesions warrants caution if repeated ESWL sessions are scheduled at short-term intervals.

Cholecystectomy, Laparoscopic↗

Fecal occult blood testing: comparative evaluation of a two-hole versus a three-hole single slide test.

The aim of this study was to analyze the effectiveness of the three-hole fecal occult blood test hemoCARE in the detection of colorectal neoplasia in asymptomatic individuals in comparison with the conventional two-hole single slide test Hemoccult. Tests were distributed to 10,269 subjects older than 45 years. A total of 62.8% of the participants returned both tests, which were positive in 374 (5.8%). The diagnostic evaluation of 208 cases revealed 57 colorectal adenomas and carcinomas. The hemoCARE test was associated with a larger number of false-positive results than the Hemoccult test (p < 0.01). Fecal occult blood testing with the three-hole test demonstrated a significant increase in the yield of colorectal neoplasms as compared with the two-hole test (57 vs. 48 detected colorectal neoplasms; p < 0.01) without modifying the positive predictive value.

Colorectal Neoplasms↗

[Traveler's diarrhea in Turkey. Prospective randomized therapeutic comparison of charcoal versus tannin albuminate/ethacridine lactate].

In most cases traveler's diarrhea is a self-limiting disease not requiring professional assistance. As data on self-treatment are very limited, a prospective randomized trial was performed in 620 German tourists spending a two week-holiday in Turkey. 31.6% of these travelers developed diarrhea and 186 were assigned to two treatment groups, receiving either medical coal or a combination of tannalbuminate and ethacridinlactate (TA/EL). In the TA/EL group stool frequencies significantly earlier returned to normal and complaints of moderate to severe abdominal pain were recorded less frequently (50 vs. 82.2%) than in patients receiving charcoal preparations. Both medications were well tolerated and TA/EL appeared more efficient for self medication of uncomplicated traveler's diarrhea.

Adult↗

Superoxide, hydroxyl and fatty acid radical scavenging by aminosalicylates. Direct evaluation with electron spin resonance spectroscopy.

Reactive oxygen radicals such as superoxide and hydroxyl radicals, as well as intermediate unsaturated fatty acid radicals, have been proposed as playing an important role in various diseases including inflammatory bowel disease (IBD). In this study we evaluated radical scavenger properties of aminosalicylates used in the therapy of IBD using spin trapped electron spin resonance spectroscopy. 5-Aminosalicylic acid (5-ASA), 4-aminosalicylic acid and olsalazine had superoxide radical scavenger properties (IC50 = 0.4, 0.4 and 1.0 mM, respectively). 5-ASA and benzalazine also inhibited hydroxyl radicals (IC50 = 6.5 mM). Fatty acid radicals were not inhibited by aminosalicylates. Our results support the hypothesis that therapeutically active compounds may be oxygen radical scavengers and that fatty acid radical scavenging has to be performed by drugs other than aminosalicylates.

Aminosalicylic Acid↗

Ursodeoxycholic acid for treatment of primary sclerosing cholangitis: a placebo-controlled trial.

The efficacy and safety of ursodeoxycholic acid for the treatment of primary sclerosing cholangitis were evaluated in a prospective, randomized, double-blind, placebo-controlled trial. Fourteen patients with primary sclerosing cholangitis documented by cholestatic serum enzyme pattern, liver histological appearance and endoscopic retrograde cholangiography were included in the trial. Six patients received ursodeoxycholic acid (13 to 15 mg/kg body wt/day), and eight patients received placebo. Two patients had to be withdrawn from the study, one because of UDCA-related diarrhea and the other because of worsening of the disease during placebo treatment. Patients in the ursodeoxycholic acid group improved significantly during 1 yr of treatment with respect to serum levels of bilirubin (median = -50%), alkaline phosphatase (median = -67%), gamma-glutamyltransferase (median = -53%), AST (median = -54%) and ALT (median = -36%) compared with the placebo group, but not with respect to serum levels of hydrophobic bile acids. During ursodeoxycholic acid treatment, histopathological features also improved significantly, as evaluated by multiparametric score. Expression of human leukocyte antigen class I molecules appeared to be markedly reduced on liver cells after ursodeoxycholic acid treatment. We conclude that ursodeoxycholic acid is beneficial in reducing disease activity in patients with primary sclerosing cholangitis.

Adolescent↗

Olsalazine-related diarrhoea: does rat intestine adapt in vivo?

Diarrhoea may occur in up to 10% of patients with ulcerative colitis treated with olsalazine, the azolinked dimer of 5-aminosalicylic acid. However, this symptom often disappears despite continued drug medication. To examine reversibility of and adaptation to olsalazine effects on intestinal absorption, rats were fed olsalazine (4 mg/100 g body weight/day) for 0 (controls), 12, 24, and 32 days. Jejunal, ileal, and colonic loops were perfused in situ with buffer or olsalazine (11.6 mM) in a pendular perfusion system. Water and electrolyte absorption was inhibited in all intestinal segments (p less than 0.001). In the proximal small intestine, however, sodium absorption was inhibited by 61%, whereas chloride and potassium absorptions were turned into net secretion. In contrast, in ileal and colonic segments sodium, chloride, and potassium absorptions were turned into a net secretion. All inhibitory effects were reversible within a short time. Intestinal absorption remained inhibitable compared with controls (p = not significant) after chronic administration of olsalazine even for 1 month. Jejunal monosaccharide absorption was not altered by acute olsalazine perfusion. In the ileum, glucose absorption was significantly inhibited, but the inhibitory capacity of acute olsalazine application decreased significantly (p less than 0.05) depending on duration of olsalazine pretreatment (51% (controls) versus 38% (32 days)). These results point to a complex, acute, but fully reversible effect of olsalazine on intestinal passive and chloride-coupled absorptive processes. Since a mucosal adaptation to these diarrheogenic effects does not occur, the resulting increase in fluid load on the diseased colon may be important in the pathogenesis of olsalazine-related diarrhoea.

Adaptation, Physiological↗