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Biomedical subjects

W E Fleig

Publications and source records attributed to W E Fleig.

At least 37 records · Page 2Linked to original sources
PubMed2003

6-thioguanine--efficacy and safety in chronic active Crohn's disease.

BACKGROUND: : Azathioprine and mercaptopurine are commonly used in chronic active Crohn's disease. They share the disadvantage of a delayed onset of action and potentially serious side-effects, and are metabolized to thioguanine nucleotides which are thought to be the active metabolites. The direct use of 6-thioguanine may offer a more rapid and safer alternative. We conducted an open prospective study to investigate the efficacy and safety of 6-thioguanine in chronic active Crohn's disease. METHODS: : Thirty-seven patients with chronic active Crohn's disease and a Crohn's disease activity index of > 150 were enrolled in this study. Inclusion criteria were steroid dependence (n = 19), steroid refractoriness (n = 9) and/or intolerance (n = 16) or refractoriness (n = 6) to azathioprine. Patients were treated with 40 mg/day of 6-thioguanine for 24 weeks; a dose escalation to 80 mg was allowed at week 12. Remission was defined as a Crohn's disease activity index of < 150 associated with a decrease of > 70 points; response was defined as a decrease of > 70 points in the Crohn's disease activity index. RESULTS: : In the intention-to-treat analysis, 13 of 37 patients achieved remission (35%). Twelve of these 13 patients achieved remission after 4 weeks. Fifty-seven per cent of patients (21/37) achieved a response. The mean Crohn's disease activity index decreased from 284 +/- 74 to 153 +/- 101. 6-Thioguanine was more effective in azathioprine-intolerant than in azathioprine-refractory patients. Twelve of 16 patients intolerant to azathioprine tolerated 6-thioguanine. Adverse events included phototoxicity, pancreatitis, headache, nausea, alopecia, arthralgia, minor infections and reversible elevation of transaminases. Six patients required discontinuation of medication, two because of leucopenia. CONCLUSIONS: : In this patient group with chronic active Crohn's disease, 6-thioguanine appeared to be effective with acceptable short-term toxicity, but long-term controlled trials are clearly needed to further define its role.

Adult↗
PubMed2003

[Acute upper gastrointestinal hemorrhage. Diagnosis and management].

Upper gastrointestinal hemorrhage calls for a team approach. Early endotracheal intubation of unconscious patients helps to prevent aspiration. Erythromycin i.v. 20 min. before emergency endoscopy improves the diagnostic yield. Patients without increased risk of rebleeding may be treated on an outpatient basis. Band ligation is the gold standard for acute variceal bleeding. Terlipressin, somatostatin and octreotide are equally effective but require additional measures for prevention of late recurrence. Somatostatin and analogues used as adjunct to ligation slightly reduce the risk of rebleeding but not of death. Three to seven days of prophylactic antibiotics decrease the risk of uncontrolled or recurrent bleeding. Therapeutic failures are rescued by transjugular intrahepatic portosystemic shunting (TIPS). Patients with nonvaricose bleeding should only be treated when active hemorrhage or a "visible vessel" is found. First line treatment is endoscopic injection of diluted adrenalin or isotonic saline. Thermal coagulation is an alternative. Tissue-destructing sclerosants should be avoided. Clipping and injection of fibrin glue are second and third line measures. Proton pump inhibitors improve endoscopic hemostasis, however, it is unclear whether high i.v. doses are required. H. pylori must be eradicated to prevent late recurrence. Rebleeding is treated endoscopically with angiographic intervention or surgery as rescue measures.

Acute Disease↗
PubMed2001

Ofloxacin and ursodeoxycholic acid versus ursodeoxycholic acid alone to prevent occlusion of biliary stents: a prospective, randomized trial.

BACKGROUND AND STUDY AIMS: Biliary plastic stents are highly effective in the treatment of malignant biliary obstruction, but may become occluded over time, leading to jaundice and cholangitis. Stent occlusion is thought to be caused by bacterial adhesion and formation of biofilm. This study was carried out to assess whether treatment with ofloxacin in combination with ursodeoxycholic acid is superior to ursodeoxycholic acid alone in preventing stent occlusion. PATIENTS AND METHODS: Patients with obstructive jaundice due to inoperable malignant disease underwent placement of a straight 11.5-Fr polyethylene stent. After stent insertion, the patients were randomly assigned to receive either ofloxacin (200 mg b.i.d.) with ursodeoxycholic acid (250 mg t.i.d.) or ursodeoxycholic acid alone. The end points of the study were the frequency of stent occlusions, the time to stent occlusion, and the safety of the two regimens. RESULTS: Fifty-two patients were enrolled, of whom 26 were assigned to the combined therapy group and 26 to the control group. Thirty patients were suffering from pancreatic cancer, 13 from gallbladder or bile duct cancer, and nine had metastases from other malignant tumors. Eight stent occlusions (31%) occurred in the ofloxacin group and six (23 %) in the control group (P = 0.76). The mean times to stent occlusion were 95 +/- 9 days and 101 +/- 9 days, respectively (P = 0.91). No significant differences regarding survival time or safety were observed between the two groups. CONCLUSIONS: Ofloxacin in combination with ursodeoxycholic acid is not superior to ursodeoxycholic acid alone in preventing stent occlusion in patients with malignant obstructive jaundice.

Aged↗
PubMed2000

Induction of cytochrome P450 (CYP)1A1, CYP1A2, and CYP3A4 but not of CYP2C9, CYP2C19, multidrug resistance (MDR-1) and multidrug resistance associated protein (MRP-1) by prototypical inducers in human hepatocytes.

Human hepatocytes cultured serum-free for up to 6 weeks were used to study expression and induction of enzymes and membrane transport proteins involved in drug metabolism. Phase I drug metabolizing enzymes cytochrome P450 (CYP)1A1, CYP1A2, CYP2C9, CYP2C19, CYP2E1, and CYP3A4 were detected by Western blot analyses and, when appropriate, by enzymatic assays for ethoxyresorufin-O-deethylase(EROD)-activity and testosterone-6beta-hydroxylase(T6H)-activity. Expression of the membrane transporter multi-drug resistance protein (P-glycoprotein, MDR-1), multidrug resistance-associated protein (MRP-1), and lung-resistance protein (LRP) was maintained during the culture as detected by RT-PCR and Western blot analyses. Model inducers like rifampicin, phenobarbital, or 3-methylcholanthrene and beta-naphtoflavone were able to induce CYP1A or CYP3A4 as well as EROD or T6H activities for up to 30 days. CYP2C9, CYP2C19 and CYP2E1 expression was maintained but not inducible for 48 days. Also, rifampicin and phenobarbital were unable to increase MDR-1 and MRP-1 protein levels significantly.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Serum-free, long-term cultures of human hepatocytes: maintenance of cell morphology, transcription factors, and liver-specific functions.

Since human hepatocytes are available only in limited number, the development of a serum-free culture system for long-term cultivation of differentiated and functional hepatocytes is of great importance. Here we describe the culture of human hepatocytes in a chemically defined serum-free medium for up to 5 weeks. Cell morphology was assayed by light and electron microscopy and revealed a well-preserved cellular morphology. Marker proteins for epithelial and bile duct cells, cytokeratin (CK) 18 and 19, and liver-specific proteins, like phosphoenolpyruvate carboxykinase-2 (PCK2) and serum proteins, were expressed. Liver-enriched transcription factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and hepatocyte nuclear factor-4 (HNF-4), cytokine and mitogen activated factors (nuclear factor kappa B) NFkappaB, and activator protein-1 (AP-1) were maintained and active for several weeks in our cultures. In summary, our serum-free culture system allows the culture of differentiated human hepatocytes for several weeks. It may serve as a model system for metabolic, pharmacologic-toxicologic studies, and studies on human pathogens under defined chemical conditions.

Blood Proteins↗
PubMed2000

Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI.

BACKGROUND & AIMS: This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection. METHODS: In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model. RESULTS: Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003). CONCLUSIONS: Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.

Adult↗
PubMed2000

Hepatic arterial blood flow velocities: assessment by transcutaneous and intravascular Doppler sonography.

BACKGROUND/AIMS: Doppler sonography has been used to assess hepatic arterial perfusion in a number of published reports. However, adequate validation studies are available for neither the transcutaneous nor the intravascular Doppler approach. The aim of this comparative study was to assess hepatic arterial perfusion with both methods. METHODS: In 15 patients the right hepatic artery was examined with intravascular and transcutaneous Doppler sonography after calibration of Doppler devices in vitro with a thread model. The measurements were performed simultaneously in five and separately within 24 h in 10 patients. RESULTS: In vitro, the correlations between the velocities of the thread and the velocities as determined by intravascular (r=1.0, p<0.001) and transcutaneous Doppler sonography (r=1.0, p<0.001) were excellent. In vivo, the best correlation was found for systolic peak velocities (intravascular: 58.5+/-18.1 cm/s, mean+/-standard deviation, transcutaneous: 58.2+/-25.2 cm/s, r=0.63, p=0.01). Although lower mean (intravascular: 26.5+/-7.7 cm/s, transcutaneous: 32.5+/-14.4 cm/s) and end-diastolic velocities (intravascular: 11.5+/-4.0 cm/s, transcutaneous: 18.4+/-8.6 cm/s) were found with intravascular compared to transcutaneous Doppler sonography, significant correlations were demonstrable between results obtained by both methods (r=0.63, p=0.01 for mean and r=0.57, p=0.025 for diastolic velocities). Similarly, the calculated resistive (intravascular: 0.79+/-0.07, transcutaneous: 0.68+/-0.06, r=0.65, p=0.009) and pulsatility indices (intravascular: 1.78+/-0.47, transcutaneous: 1.26+/-0.25, r=0.55, p=0.034) were somewhat higher using the intravascular device, but correlated well with the numbers obtained by the transcutaneous approach. CONCLUSIONS: The data suggest that with use of different Doppler devices, systolic velocities are the most suitable parameter for Doppler assessment of hepatic arterial perfusion.

Adult↗