PubMed Health⌕ Search

Biomedical subjects

W E Fleig

Publications and source records attributed to W E Fleig.

At least 19 recordsLinked to original sources
PubMed2006

Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).

BACKGROUND: Combinations of gemcitabine-oxaliplatin, gemcitabine-5-fluorouracil (5-FU) and 5-FU-oxaliplatin have synergistic activity and nonoverlapping adverse effect profiles. This trial assessed efficacy and safety of the triple combination gemcitabine-oxaliplatin and infusional 5-FU in patients with locally advanced (n=11) or metastatic (n=32) pancreatic adenocarcinoma. PATIENTS AND METHODS: A total of 43 eligible patients were treated with intravenous infusions of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2 h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle. RESULTS: Among all 43 patients, the tumor response rate was 19% [95% confidence interval 7% to 30%]. Nine patients were nonassessable for response because they did not complete the first two cycles of chemotherapy due to rapid disease progression, early death or treatment refusal. One patient was lost to follow-up. Median time to progression and overall survival were 5.7 and 7.5 months. Principal grade III/IV toxic effects were leucopenia in 11 (2%), thrombocytopenia in 13 (2%), nausea in 13 (0%), anorexia 16 (7%) and sensory neuropathy in 18 (0%) of patients. Unexpected cardiotoxicity was observed in this trial. CONCLUSION: Response rates and survival of the three-drug combination compare favorably with single-agent gemcitabine, but do not exceed results for doublets.

Adenocarcinoma↗
PubMed2005

Diagnosis of small bowel Crohn's disease: a prospective comparison of capsule endoscopy with magnetic resonance imaging and fluoroscopic enteroclysis.

BACKGROUND AND AIMS: The diagnostic yield of capsule endoscopy (CE) compared with magnetic resonance imaging (MRI) in small bowel Crohn's disease is not well established. We prospectively investigated CE, MRI, and double contrast fluoroscopy in patients with suspected small bowel Crohn's disease. METHODS: Fifty two consecutive patients (39 females, 13 males) were investigated by MRI, fluoroscopy and--if bowel obstruction could be excluded--by CE. In 25, Crohn's disease was newly suspected while the diagnosis of Crohn's disease (non-small bowel) had been previously established in 27. RESULTS: Small bowel Crohn's disease was diagnosed in 41 of 52 patients (79%). CE was not accomplished in 14 patients due to bowel strictures. Of the remaining 27 patients, CE, MRI, and fluoroscopy detected small bowel Crohn's disease in 25 (93%), 21 (78%), and 7 (of 21; 33%) cases, respectively. CE was the only diagnostic tool in four patients. CE was slightly more sensitive than MRI (12 v 10 of 13 in suspected Crohn's disease and 13 v 11 of 14 in established Crohn's disease). MRI detected inflammatory conglomerates and enteric fistulae in three and two cases, respectively. CONCLUSION: CE and MRI are complementary methods for diagnosing small bowel Crohn's disease. CE is capable of detecting limited mucosal lesions that may be missed by MRI, but awareness of bowel obstruction is mandatory. In contrast, MRI is helpful in identifying transmural Crohn's disease and extraluminal lesions, and may exclude strictures.

Acute Disease↗
PubMed2005

Chemotherapy for advanced gastric cancer.

BACKGROUND: Gastric cancer currently ranks second in global cancer mortality. Most patients are either diagnosed at an advanced stage, or develop a relapse after apparently curative operation. Apart from supportive measures, systemic chemotherapy is the only treatment option available in this situation. OBJECTIVES: To assess the effect of chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapy regimens in advanced gastric cancer. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE and EMBASE up to February 2004 and reference lists of articles. We also contacted pharmaceutical companies as well as national and international experts. SELECTION CRITERIA: Randomised controlled trials on systemic intravenous chemotherapy versus best supportive care, combination versus single agent chemotherapy and different combination chemotherapies in advanced gastric cancer. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. MAIN RESULTS: Chemotherapy versus best supportive care consistently demonstrated a significant benefit in terms of overall survival in favour of the group receiving chemotherapy (Hazard Ratios (HR) 0.39; 95% confidence intervals (CI) 0.28 to 0.52). Combination versus single-agent chemotherapy provides evidence for a survival benefit in favour of combination chemotherapy (HR 0.85; 95% CI 0.76 to 0.96). Numbers included in these comparisons were 184 and 1338 participants respectively. This benefit is achieved at the price of increased toxicity in the combination chemotherapy arms. When comparing 5-FU/cisplatin-containing combination therapy regimens with anthracyclines versus those without anthracyclines (HR 0.77; 95% CI 0.62 to 0.95 based on 501 participants) and 5-FU/anthracycline-containing combinations with cisplatin versus those without cisplatin (HR 0.83; 95% CI 0.76 to 0.91 based on 1147 participants), there was a significant survival benefit for regimens including 5-FU, anthracyclines and cisplatin. AUTHORS' CONCLUSIONS: Chemotherapy significantly improves survival in comparison to best supportive care. In addition, combination chemotherapy improves survival compared to single-agent 5-FU, but the effect size is much smaller. Among the combination chemotherapy regimens studied, best survival results are achieved with regimens containing 5-FU, anthracyclines and cisplatin. In this category, ECF (epirubicin, cisplatin and continuous infusion 5-FU) is tolerated best.

Anthracyclines↗
PubMed2005

[Early diagnosis of liver diseases].

In Germany, liver diseases are the leading cause of death through illness among 30 to 45 year olds. Most are chronic diseases and timely preventative or therapeutic measures could avert their manifestation or at least the following complications. Currently, screening for liver diseases is focused on specific groups at risk such as patients with alcohol abuse, relatives of patients with a genetic disease or individuals at risk of an infection with a viral hepatitis. For some diseases, studies have been started to test the practicability of population screening, which has already been successfully implemented for Hepatitis B and C in blood donors. Screening is also recommended for advanced liver disease. It helps to detect the development of cirrhosis and its complications namely varices and hepatocellular carcinoma.

Adult↗
PubMed2005

Hepatic arterial doppler sonography in patients with cirrhosis and controls: observer and equipment variability with use of the ultrasonic contrast agent SHU 508A.

PURPOSE: The aims of this study on hepatic arterial Doppler sonography were to ascertain interobserver and interequipment variability, to investigate any potential artificial influence of the ultrasonic contrast agent on the Doppler measurements and to compare the results in healthy and cirrhotic subjects. METHODS: Doppler sonography of the left hepatic artery was performed in nine healthy and nine cirrhotic subjects by three independent observers using three different devices. Continuous infusion of the ultrasonic contrast agent SHU 508A and placebo were administered in a double blind fashion. Systolic, mean and end diastolic peak velocities as well as resistive and pulsatility indices were measured. RESULTS: Equipment associated variances (5.8 - 12.7 %) of the five Doppler parameters were greater than interobserver variances (0.3 - 3.6 %). No significant differences were observed between the velocities using ultrasonic contrast agent and placebo. Systolic (65.9 +/- 3.6 vs. 47.7 +/- 4.2 cm/s mean +/- SE, p = 0.02) and mean peak velocity (35.4 +/- 1.6 vs. 24.5 +/- 1.8 cm/s, p = 0.007) were significantly higher in cirrhotic than in healthy subjects whereas the resistive and pulsatility indices were not different. CONCLUSIONS: Doppler sonography of the left hepatic artery performed by various observers is reproducible as long as the same device is used. Under clinical conditions, velocities are correctly measured with the use of ultrasonic contrast agent and are elevated in patients with cirrhosis.

Adult↗
PubMed2004

[Spontaneous bacterial peritonitis (SBP). Retrospective and prospective data from a multicenter study on prevalence, diagnosis and therapy in Germany].

BACKGROUND: Data regarding the prevalence of SBP in patients with ascites or the diagnostic and therapeutic management of SBP in Germany are lacking. PATIENTS AND METHODS: In a multicenter study (40 hospitals), retrospective, then prospective data were collected investigating the prevalence of SBP in patients with ascites and the pertinent diagnostic and therapeutic management. In 272 prospectively entered patients with ascites (cirrhosis/malignant ascites/other: n = 227/42/3) a diagnostic paracentesis was performed and SBP diagnosed using the ascitic neutrophil count. History, clinical symptoms and laboratory findings were recorded and potential risk factors analysed by univariate analysis and stepwise logistic regression. SBP was treated with a standard dose of a third-generation cephalosporin. RESULTS: In the retrospective study, SBP was diagnosed in 648 of 4,697 patients with ascites (14 %). Employed diagnostic and therapeutic pathways were not effective in several hospital departments. In the prospective trial, SBP was found in 134 of 272 patients with ascites (49,3 %). Frequency of symptoms was significantly different in patients either with or without SBP, as were macroscopic aspect of ascites, urine excretion and several biochemical parameters. However, their diagnostic precision was unsatisfactory. Predictive factors for SBP were previous paracentesis, endoscopic procedures and a history of abdominal pain. Treatment was effective in 83,5 % of cases. Inhospital mortality was 10 %. CONCLUSION: The prevalence of SBP in hospitalised patients with ascites in Germany is similar to that in southern Europe and USA. Symptoms alone lack sufficient diagnostic accuracy. Third-generation cephalosporin is an effective antibiotic in SBP. Pertinent diagnostic and therapeutic management calls for improvement.

Analysis of Variance↗
PubMed2004

[Portal vein thrombosis in a patient with lowered protein S level].

HISTORY AND CLINICAL FINDINGS: In a 39-year-old man with increasing spasmodic epigastric pain, nausea and vomiting, varices of the esophagus and the gastric fundus were found endoscopically. INVESTIGATIONS: A portal vein thrombosis and a consecutive thrombosis of the splenic vein were diagnosed by colour Doppler sonography and angio CT. A protein S deficiency (59 %) was found to be the underlying illness. TREATMENT AND COURSE: The thrombosis and the resulting clinical symptoms completely resolved shortly after starting therapeutic heparinization. For six months, the patient has been without complaints or clinical symptoms. CONCLUSION: Hence, an isolated protein S deficiency can be the cause for a portal vein thrombosis.

Adult↗
PubMed2004

Thioguanine-nucleotides do not predict efficacy of tioguanine in Crohn's disease.

BACKGROUND: 6-Thioguanine-nucleotides seem to be the active metabolites of thiopurine therapy, and their monitoring has been considered a useful tool for optimizing response in inflammatory bowel diseases. Tioguanine (thioguanine) therapy results in much higher levels of 6-thioguanine-nucleotide levels when compared with azathioprine or mercaptopurine. AIM: To elucidate the influence of 6-thioguanine-nucleotide and methylated 6-thioguanine-nucleotide levels under tioguanine on efficacy and toxicity in Crohn's disease. METHODS: 6-Thioguanine-nucleotide and methylated 6-tioguanine-nucleotide levels were measured regularly in 26 Crohn's disease patients treated with tioguanine. Nucleotide levels were related to efficacy and toxicity. RESULTS: 6-Thioguanine-nucleotide levels rose very high [median 1241 pmol/8 x 10(8) red blood cells (range 313-1853)]. Methylated 6-thioguanine-nucleotide levels were detected in all patients [491 pmol/8 x 10(8) red blood cells (154-1775)]. 6-Thioguanine-nucleotide and methylated 6-thioguanine-nucleotide concentrations correlated significantly (r = 0.7, P < 0.0001). Nucleotide levels from patients achieving remission (n = 14) did not differ significantly from non-remitters (n = 12) [6-thioguanine-nucleotide: 1077 (599-2160) vs. 1210 (534-4665); methylated 6-thioguanine-nucleotide: 510 (214-1222) vs. 421 (145-1284)]. One patient with intermediate thiopurine S-methyltransferase activity experienced bone marrow toxicity upon dose escalation parallel with excessively high thioguanine-nucleotide levels. CONCLUSIONS: 6-Thioguanine-nucleotide as well as methylated 6-thioguanine-nucleotide levels under tioguanine therapy were not related to efficacy. This suggests that monitoring of 6-thioguanine-nucleotide levels is not a useful tool to predict response to thiopurines.

Adult↗
PubMed2004

Expanding hepatocytes in vitro before cell transplantation: donor age-dependent proliferative capacity of cultured human hepatocytes.

BACKGROUND: For hepatocyte transplantation as well as experimental purposes, it would be advantageous to be able to expand human hepatocytes in vitro. However, under serum-free conditions, even with supplements of HGF (hepatic growth factor) and EGF (epidermal growth factor), proliferation of human hepatocytes is hampered. The aim of this study was to identify differences in the proliferative capacity of cultured primary human hepatocytes related to the age of the liver donors. METHODS: Proliferation was determined by BrdU-uptake, ploidy was measured using propidium iodide staining and flow cytometry, and the expression of cell cycle related proteins was determined by Western blotting. RESULTS: During the initial culture, juvenile hepatocytes proliferated better than adult hepatocytes. The proliferation rate declined to barely detectable levels after 8 days in culture in both juvenile and adult hepatocytes. The higher proliferative capacity of juvenile hepatocytes was associated with a larger fraction of diploid cells and a higher viability. The expression of regulatory cell cycle related proteins was higher in juvenile than in adult hepatocytes. CONCLUSIONS: The proliferation of human hepatocytes in vitro is critically related to a large fraction of diploid hepatocytes. The expression of regulatory cell cycle proteins reflects the proliferative capacity of cultured human hepatocytes. Juvenile as compared to adult human hepatocytes may be better suited for expansion in culture and could have a stronger repopulation capacity in vivo.

Age Factors↗
PubMed2003

13C-Methacetin metabolism in patients with cirrhosis: relation to disease severity, haemoglobin content and oxygen supply.

BACKGROUND: Hypoxia may contribute to impairment of liver function and thus interfere with results of liver tests. In patients with cirrhosis, cytochrome P-450 mediated metabolism of substrates is facilitated in the presence of supplemental oxygen. It has not been studied how this relates to liver function and haemoglobin content. AIM: We questioned how oxygen supplementation would influence the hepatic microsomal function as assessed by the 13C-methacetin breath test in patients with cirrhosis of different severity and different degrees of anaemia. METHODS: 13C/12C ratios in exhaled breath assessed by non-dispersive infrared spectrometry were studied in 34 patients with cirrhosis (Child A/B/C 9/17/8) after administration of 75 mg 13C-methacetin p.o. with and without oxygen inhalation (4 L/min). RESULTS: In patients breathing room air the total amount of 13C exhaled weakly correlated both with the Child-Pugh score (r = - 0.41, P < 0.02) and haemoglobin concentrations (r = 0.46; p = 0.006). Oxygen supplementation increased the total amount of 13C exhaled by 68 +/- 90% (P < 0.001). This effect was similar in Child-Pugh classes A (43 +/- 55%), B (83 +/- 80%) and C (66 +/- 123%) and not related to the Child-Pugh score. CONCLUSIONS: Our results suggest that tests of microsomal liver function are independently influenced both by oxygen delivery and the Child-Pugh score.

Acetamides↗