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M Gschwantler

Publications and source records attributed to M Gschwantler.

At least 19 recordsLinked to original sources

Primary interferon resistance and treatment response in chronic hepatitis C infection: a pilot study.

Only 30% of patients with chronic hepatitis C virus genotype 1 (HCV-1) infection achieve a sustained virological response to interferon and ribavirin combination therapy. We prospectively assessed decline in viral load 24 h after one dose of interferon alfa as a predictor of non-response to 6 months of treatment with interferon and ribavirin. Interferon sensitivity was measured before initiation of combination therapy. We measured viral load in 29 consecutive patients, who had not previously been treated with interferon and who were chronically infected with HCV-1 within 24 h after one dose of 5 MU or 10 MU interferon alfa-2b, and 14 days of daily 5 MU interferon alfa-2b. A 24 h viral load decline by less than 70% of baseline after 5 MU interferon was the best pretreatment measure to identify non-responders (specificity 100%, n=10, 95% CI 74-100], sensitivity 83% [15/18], 59-96]).

Adult↗

Combination of interferon induction therapy and ribavirin in chronic hepatitis C.

The initial clearance of hepatitis C virus (HCV) during interferon-alfa therapy is dose-dependent. Therefore, higher initial interferon doses (induction therapy) may improve treatment results. This concept was tested in a prospective, randomized controlled trial. Previously untreated patients with chronic hepatitis C were randomized to receive 3 different interferon doses during the first 14 weeks of therapy (Group A, n = 130: 10 MU IntronA [AESCA-Schering Plough, Traiskirchen, Austria]/day for 2 weeks, followed by 10 MU/2 days for 12 weeks; Group B, n = 124: 5 MU/day for 14 weeks; Group C, n = 119; 5 MU/2 days for 14 weeks) followed in all by 5 MU/2 days for 24 weeks. Throughout the whole study all patients received 1 to 1.2 g ribavirin/day. On treatment, no differences in viral clearance rates were observed. Sustained response rates were also not different among the groups (A: 48.5%, B and C: 41.3%, intent to treat). When data were analyzed according to genotypes, sustained response was almost twice as high in patients with genotype 1 receiving high-dose interferon induction therapy (A: 44.2%, B: 28.6%, C: 27%, P <.05). In contrast, results were not different in genotype 3a patients (A: 61.3%, B: 75.9%, C: 56.3%; P >.1). These data indicate that high-dose interferon induction therapy may improve the outcome of interferon/ribavirin combination therapy in genotype 1 patients.

Adult↗

Development of insulin-dependent diabetes mellitus in a patient with chronic hepatitis C during therapy with interferon-alpha.

Interferon (IFN)-alpha is used for the treatment of chronic viral hepatitis. It has been associated with various forms of autoimmune disease, e.g. autoimmune hepatitis, Hashimoto thyroiditis and insulin-dependent diabetes mellitus. Further, an increase of insulin resistance and development of non-insulin-dependent diabetes mellitus has been described after treatment with IFN-alpha. Several studies have investigated the induction of different autoimmune markers by IFN-alpha, but only few specified patients who developed insulin-dependent diabetes mellitus. We report the case of a 37-year-old man with chronic hepatitis C who was treated with IFN-alpha plus ribavirin. Thirty weeks after the start of treatment, the patient developed insulin-dependent diabetes mellitus and therapy was withdrawn. HLA typing showed an HLA-DR1,3 phenotype. At manifestation of diabetes mellitus, the C-peptide level was 0.37 ng/ml (normal range 0.5-3 ng/ml). The patient had a positive family history for type 2 diabetes. Several autoimmune markers were investigated before, during and 6 months after withdrawal of antiviral treatment. High titres of glutamic acid decarboxylase (GAD) antibodies were present before therapy. A significant increase in titres of islet cell antibodies, parietal cell antibodies and sperm antibodies was present after 14 weeks of IFN-alpha treatment. Six months after withdrawal of IFN-alpha therapy, these antibodies had significantly decreased whereas GAD antibodies remained unchanged. There was no clinical sign of any other autoimmune disease. Our data show that, in patients with a predisposition to insulin-dependent diabetes mellitus, the disease may become manifest as a side-effect during therapy with IFN-alpha. Several pathogenetic factors may be involved in this process, and, in addition to IFN-alpha, hepatitis C itself may induce autoimmune mechanisms. We conclude that screening for autoantibodies specific for type 1 diabetes should be performed before the start of IFN-alpha treatment. In patients found to be at increased risk of developing diabetes mellitus type 1, monitoring of titres of these antibodies during therapy could help to assess the individual risk-benefit ratio of IFN-alpha treatment.

Adult↗

Treatment of patients with chronic hepatitis C not responding to interferon with high-dose interferon alpha with or without ribavirin: final results of a prospective randomized trial. Austrian Hepatitis Study Group.

OBJECTIVE: To investigate the efficacy of high-dose interferon alpha (IFN-alpha) with or without ribavirin in interferon (IFN) non-responders. STUDY DESIGN: 304 chronic hepatitis C patients received 5 MU IFN-alpha2b (IntronA, Schering-Plough, Kenilworth, NJ, USA) three times a week for 3 months. Non-responders were randomized either to continue with IFN (IFN 5 MU/TIW followed by 10 MU/TIW, each for 3 months) alone (group A: n = 76, m: f = 54: 22, age 45.7 +/- 12 years, 16% cirrhosis, alanine aminotransferase [ALT] 66 +/- 35 U/l) or in combination with ribavirin (approximately 14 mg/kg/day) (group B: n = 81, m: f = 57: 24, age 48.2 +/- 12 years, 17% cirrhosis, ALT 71 +/- 40 U/l). At the end of treatment, patients were followed for 6 months. MAIN OUTCOME MEASURES: Virological response at end of treatment and 6 months thereafter. SETTING: University hospitals and tertiary referral centres. RESULTS: At the end of treatment, eight (10.8%) and 25 (31.3%, P= 0.0066) patients were HCV-RNA negative, and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop-outs in each group. Six months after treatment, only one patient in group A (1.3%) and seven patients (8.6%, P= 0.06) in group B had normal ALT and undetectable serum HCV-RNA. CONCLUSIONS: A combination of high-dose IFN with ribavirin induces a short-lasting complete response in about one-third of IFN-non-responders.

Adult↗

Helicobacter pylori and gastric cancer:current status of the Austrain Czech German gastric cancer prevention trial (PRISMA Study).

AIM: To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease. METHODS: It is a prospective, randomized, double blind, placebo controlled multinational multicenter trial. Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacter pylori gastritis are randomized to receive a 7 day course of omeprazole 2 X 20mg, clarithromycin 2 X 500mg, and amoxicillin 2 X 1g for 7 days, or omeprazole 2 X 20mg plus placebo. Follow-up endoscopy is scheduled 3 months after therapy, and thereafter in one-year intervals. Predefined study endpoints are gastric cancer, precancerous lesions (dysplasia, adenoma), other cancers, and death. RESULTS: Since March 1998, 1524 target patients have been screened, 279 patients (18.3%) had a corpus dominant type of H. pylori gastritis, and 167 of those were randomized (58.8%). In the active treatment group (r = 86), H. pylori infection infection was cured in 88.9% of patients. Currently, the cumulative follow-up time is 3046 months (253.38 patient years, median follow up 16 months). So far, none of the patients developed gastric cancer or any precancerous lesion. Three (1.8%) patients reached study endpoints other than gastric cancer. CONCLUSION: Among men between 55 and 65 years of age, the gastric cancer phenotype of H. pylori gastritis appears to be more common than expected. Further follow up and continuing recruitment are necessary to fulfil the main aim of the study.

Amoxicillin↗

Reconstructive intestinal surgery after open management of severe intraabdominal infection.

Open management (OM) of severe intraabdominal infection often is complicated by fistula formation and the need for complex reconstructive procedures. From 1988 to 1998 a series of 145 patients were treated by OM. Of these patients, 24 developed intestinal fistulas and 42 had to be treated by discontinuity resections prior to OM for intestinal perforations or anastomotic insufficiency. Of the patients with fistulas or enterostomies, 61% survived. Reconstructive surgery was performed after infections had completely subsided. Patients were examined on follow-up, and the quality of life was assessed by 36-item short-form health survey questionnaires. Restorative surgery was performed in 32 of 40 patients 102 days (median) after beginning OM. All patients survived. Anastomotic leakage developed in six patients (18%). Thirty patients (94%) were followed up; 70% indicated their quality of life to be good. Despite a higher rate of anastomotic problems than with elective visceral operations, reconstructive intestinal surgery after OM may be performed without mortality and satisfying long-term outcome.

Abdominal Abscess↗

[Physiopathology of Helicobacter pylori infections].

Helicobacter pylori (H.p.) causes active chronic gastritis in nearly all infected patients. Cytotoxic factors elaborated by H.p. as well as autoimmune cell damage from the abundant inflammatory response contribute to gastric epithelial cell injury. Antrum gastritis increases gastrin release. The impact of H.p.-infection on gastric acid physiology is complex and usually results in increased gastric acid secretion in duodenal ulcer patients and diminished acid output in patients with gastric cancer. Multiple clinical outcomes including asymptomatic gastritis, duodenal ulcer, gastric ulcer, gastric carcinoma and gastric MALT lymphoma are associated with H.p.-infection. Differences in disease manifestation seem to result from a complex interaction of bacterial virulence, host factors as well as environmental factors. The acid-secretory ability of the infected individual seems to be the main variable determining outcome: Patients with high acid production typically develop antrum-predominant gastritis and are at an increased risk for duodenal ulcer. In contrast patients with low gastric acid secretion frequently develop pangastritis, which may progress to chronic atrophic gastritis and carcinoma.

Duodenal Ulcer↗

[In Process Citation]

BACKGROUND: Although the majority of surgeons regard Hartmann's operation as therapeutic standard in perforations of the colon complicated by peritonitis this procedure has been critically discussed in recent years. Advocates of one-stage techniques criticized bad postoperative results (high morbidity and mortality) and long-term outcome (low rates of intestinal restoration). The aim of our study was to investigate whether the late results after Hartmann's operation justify this criticism. METHOD: From 1982 to 1997 Hartmann's operations were performed in 103 patients for colonic perforations. In 63% of cases inflammatory diseases caused colonic complications. The average Mannheimer Peritonitis Index (MPI) was 19. Seventeen patients died postoperatively (mortality: 16.5%). In 69 patients (80%) intestinal restoration could be performed after an average interval of 122 days (complication rate: 6%, no mortality). On follow-up, patients were asked to give information on their general state, changes of housing, abdominal complaints, and quality of life. RESULTS: Data on 93% of patients could be obtained. The median follow-up time was 75 months. Eleven patients had died; the remaining 72 were investigated. 86% described the quality of their lives as good or very good; only 11% indicated severe loss of activity. Quality of life did not differ between patients in whom intestinal continuity had been restored and those in whom it had not been restored. Anastomotic structures developed in 7% of cases, always after stapled anastomosis. CONCLUSIONS: According to our results, long-term outcome after Hartmann's operation is good. 80% of patients underwent intestinal restoration with low morbidity (6%) and no mortality. A great majority of patients indicated the quality of their lives as good or very good: this assessment was not dependent on restoration of intestinal continuity.

Journal Article↗

[In Process Citation]

The aim of this study was to investigate postoperative und long-term results after radical tumor surgery in complicated colorectal cancers. One hundred and twenty-six (11.7%) of 1071 patients treated for large bowel cancer between 1986 and 1997 were operated on for bowel obstruction (84; 7.8%): or perforation (42; 3.9%). Postoperative mortality was significantly higher in complicated than in uncomplicated cancers (19% after bowel obstruction, 38% after perforation, 6% in uncomplicated cases). Development of preoperative organ dysfunction determined survival in both complications. Mortality after perforations was influenced by the degree of peritonitis and tumor stage, while patients after bowel obstruction were at greater risk in the case of cardiac comorbidity. Long-term results depended on tumor stage but not on complications. Our concept of radical tumor surgery in emergency operations was supported by the fact that long-term results of patients surviving the acute stage of complicated colorectal cancers did not differ from those of patients with uncomplicated carcinomas.

Journal Article↗

Course of platelet counts in cirrhotic patients after implantation of a transjugular intrahepatic portosystemic shunt--a prospective, controlled study.

BACKGROUND/AIMS: The pathogenesis of thrombocytopenia associated with advanced liver disease is still controversial. To study the impact of portal decompression on this hematologic complication, we conducted a prospective, controlled study to compare the course of platelet counts in patients after implantation of a transjugular intrahepatic portosystemic shunt (TIPS) with matched controls without shunts. METHODS: Fifty-five TIPS patients and 110 controls matched for age, sex, Child-Pugh class, etiology of liver disease and baseline platelet count were included, and followed for 1 year. Follow-up visits were scheduled after 1 month, after 3 months, and at 3-month intervals thereafter. RESULTS: Nonparametric Mann-Whitney U-tests revealed significantly higher platelet counts for TIPS patients as compared to controls from the 1st through the 12th month (p<0.01). During the study period, the median platelet count of TIPS patients increased by 19.7%, from 104.0/nl (IR: 68.0) to 124.5/nl (IR: 41.0). In contrast, during the same period the median platelet count of controls decreased by 17.1%, from 102.5/nl (IR: 66.0) to 85.0/nl (IR: 67.5). In the group of cases with baseline platelet counts < or =100/nl, platelet counts had increased by at least 25% at month 12 in 65% of TIPS patients, but in only 5% of controls (p<0.001). However, normalization of platelet counts, i.e. > or =150/nl, was not achieved in any case. Neither the portosystemic pressure gradient after TIPS implantation, nor the percentage of portosystemic pressure gradient reduction during the procedure was predictive of platelet response. CONCLUSIONS: TIPS implantation increases platelet counts significantly. However, portal hypertension is clearly not the only mechanism contributing to thrombocytopenia in advanced liver disease.

Adult↗

Famotidine versus omeprazole in combination with clarithromycin and metronidazole for eradication of Helicobacter pylori--a randomized, controlled trial.

BACKGROUND: One-week low-dose triple therapy is currently considered the gold standard regimen for treatment of Helicobacter pylori infection. However, the mechanisms involved in the synergy between antibiotics and proton pump inhibitors are controversial. AIMS: To test the hypothesis that acid suppression represents the crucial mechanism by which the antibacterial activity of antibiotics can be enhanced, and to assess the impact of primary resistance on treatment outcome. METHODS: One hundred and twenty patients with H. pylori infection and duodenal ulcer, gastric ulcer or non-ulcer dyspepsia were randomly assigned to a 1 week course of either famotidine 80 mg b.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (FCM group; n = 60) or omeprazole 20 mg o.d., clarithromycin 250 mg b.d. and metronidazole 500 mg b.d. (OCM group; n = 60). Gastroscopy was performed at baseline and 5 weeks after completion of treatment. H. pylori status was assessed by biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 47 of 60 patients (78%; 95% CI: 66-88%) in the FCM group, compared to 44 of 60 patients (73%; 95% CI: 60-84%) in the OCM group (N.S.). Using per protocol analysis, eradication therapy was successful in 47 of 52 patients (90%; 95% CI: 79-97%) treated with FCM and 44 of 57 patients (77%; 95% CI: 64-87%) treated with OCM (N.S.). Primary metronidazole resistance was present in 27% and primary clarithromycin resistance in 8% of strains. Overall per protocol eradication rates in strains susceptible to both antibiotics and strains with isolated metronidazole resistance were 93% and 84%, respectively. No patient with clarithromycin resistance responded to treatment. CONCLUSIONS: High-dose famotidine and omeprazole, combined with clarithromycin and metronidazole, are equally effective for eradication of H. pylori. In 1-week low-dose triple therapy, metronidazole resistance has no major impact on eradication rates whereas clarithromycin resistance is associated with a poor treatment outcome.

Adult↗

Interim analysis of a randomized controlled trial of combination of ribavirin and high dose interferon-alpha in interferon nonresponders with chronic hepatitis C.

UNLABELLED: This trial investigated the efficacy of a combination of high-dose interferon-alpha (IFN-alpha) with ribavirin in IFN nonresponders. STUDY PROTOCOL: 304 patients with chronic hepatitis C were treated with 5 MU IFN-alpha2b (IntronA(R), Schering-Plough) per TIW for 3 months. Nonresponders (defined by HCV-RNA positivity in serum after the 3 months of therapy) were randomized either to continue with IFN (5 MU IFN per TIW followed by 10 MU per TIW for each 3 months) alone (group A) or in combination with ribavirin (1-1.2 g per day) (group B). ALT was measured in monthly intervals, HCV-RNA in 3 monthly intervals. Pretreatment characteristics of the randomized patients were as follows: group A, n = 76; m/f, 54/22; 16% cirrhosis, age, 45. 7 +/- 12 years; ALT (U per litre), 66 +/- 35; group B, n = 81; m/f, 57/24; 17% cirrhosis, age, 48.2 +/- 12; ALT, 71 +/- 40. After 9 months of treatment, nine (11.6%) and 27 (32.5%, P = 0.0066) patients were HCV-RNA negative and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop-outs in group A and 15 in group B. Six months after treatment only two patients in group A (2.5%) and five (6%, P = 0.06) in group B had normal ALT and no detectable HCV-RNA in serum. In addition to the well-known side-effects of IFN the mean haemoglobin concentration dropped by 2 g per litre in group B. These data indicate that a combination of high-dose IFN with ribavirin is effective in inducing a short-lasting complete response in one-third of IFN nonresponders. Prolonged treatment with IFN/ribavirin may be necessary to obtain a sustained response.

Adult↗

Complications after surgery for necrotising pancreatitis: risk factors and prognosis.

OBJECTIVE: To evaluate risk factors, results of treatment, and prognostic influence of complications on survival from acute necrotising pancreatitis. DESIGN: Retrospective study of prospectively collected data. SETTING: Tertiary referral centre, Austria. SUBJECTS: 100 consecutive patients operated on for necrotising pancreatitis confirmed by dynamic angio-computed tomography from 1988-1997. INTERVENTIONS: 77 patients were operated on acutely followed by open management, and in 23 the operations were delayed. MAIN OUTCOME MEASURES: Morbidity, mortality, factors predisposing to complications, prognostic effect of complications on survival. RESULTS: Acute operations, alcoholic origin, APACHE II scores of > or = 10 on admission, and organ dysfunction on admission were independent factors that predisposed patients to complications. Colonic necrosis (n = 17) bleeding (n = 12) and intestinal fistulisation (n = 10) predominated. The overall mortality of complicated pancreatic necrosis was higher among patients admitted with surgical complications than in those who were not, but not significantly so (12/33 compared with 7/44 p = 0.06). Colonic necrosis (mortality 53%, relative risk: 2.45, p = 0.01), however, seemed to be of prognostic relevance. CONCLUSIONS: Complications are common in severe necrotising pancreatitis leading to organ dysfunction and need for acute operations. Colonic necrosis is an independent prognostic factor for survival.

Adult↗

Eradication of Helicobacter pylori by a 1-week course of famotidine, amoxicillin and clarithromycin.

OBJECTIVES: The combination of a proton pump inhibitor (PPI) such as omeprazole with amoxicillin and clarithromycin constitutes one of the most effective treatments for the eradication of Helicobacter pylori. Nevertheless, the mechanisms of interaction between these drugs remain unclear. It has been shown that minimal inhibitory concentration values of both antibiotics are considerably lower at neutral pH levels than in an acid environment. Further, omeprazole possesses bacteriostatic activity. To evaluate the significance of these mechanisms we replaced omeprazole with famotidine, a drug which only suppresses acid production, but has no intrinsic antimicrobial activity. METHODS: We evaluated the efficacy of a 1-week course of famotidine 80 mg b.i.d., amoxicillin 1000 mg b.i.d. and clarithromycin 500 mg b.i.d. in a pilot study (20 patients), and then confirmed our results in a larger replication study (87 patients). A total of 107 patients with H. pylori-associated duodenal ulcer (n = 54), gastric ulcer (n = 14) or non-ulcer dyspepsia (n = 39) were included. Endoscopy was performed at baseline and 4-6 weeks after discontinuation of treatment. H. pylori status was assessed by the urease test and histology. RESULTS: H. pylori was successfully eradicated in 94 of 104 patients who completed the study (90.4%; CI 95%, 83.0-95.3%). By intention-to-treat analysis, the eradication rate was 87.9% (CI 95%, 80.1-93.4%). Ulcer healing was observed in 98.1% of duodenal ulcers and 92.9% of gastric ulcers (based on per-protocol analysis). Mild side effects that did not require termination of treatment were reported by seven patients (6.7%). CONCLUSION: A 1-week course of famotidine, amoxicillin and clarithromycin is a highly effective, simple and safe eradication regimen. Our data indicate that acid suppression is the crucial mechanism by which the activity of amoxicillin and clarithromycin against H. pylori is enhanced, whereas additional antimicrobial activity or other specific effects of PPIs seem to be less important.

Adult↗

Patients' assessment and recall of surgical information after laparoscopic cholecystectomy.

BACKGROUND: While patients' needs for adequate preoperative information are generally recognized, data evaluating the effectiveness of the consultation before laparoscopic cholecystectomy have not been published until today. This prospective study was performed to investigate the success of preoperative information. METHODS: A combination of oral and written information was given to all patients in two interviews. Information concentrated on indications for surgery, operative procedures, and risks. Patients were asked to answer questionnaires 5 days after the operation. RESULTS: From January 1996 to January 1997, 200 patients were interviewed. Ninety-seven percent indicated to wish detailed information. Eighty-four percent indicated a high level of satisfaction with the presented information. While the levels of knowledge concerning indications for surgery and procedures were satisfactory in 85 and 51% respectively, only 30% were able to name at least one risk factor of laparoscopic cholecystectomy. CONCLUSION: This study demonstrated that patients' evaluation of their surgical knowledge and the process by which it was communicated to them did not correspond to their ability to recall this information after surgery.

Adolescent↗

Clinical outcome two years after implantation of a transjugular intrahepatic portosystemic shunt for recurrent variceal bleeding.

OBJECTIVE: Implantation of a transjugular intrahepatic portosystemic shunt (TIPS) is a relatively new therapy for variceal bleeding. The aim of this study was to assess clinical course 2 years after TIPS procedure. DESIGN: The study was designed as a prospective, uncontrolled cohort study. METHODS: Forty-six patients who underwent successful TIPS implantation were followed prospectively by clinical examinations, duplex sonography and portal venography. Mean follow-up in surviving patients was 24.1 +/- 9.0 months. RESULTS: The cumulative rate of survival was 80.4% at 1 year and 70.2% at 2 years. The cumulative rebleeding rate was 12.4% at 1 year and 21.3% at 2 years. The mortality rate of episodes of variceal rebleeding was 22.2%. Variceal rebleeding was associated with shunt abnormalities, and successful shunt revision resulted in control of the bleeding. The cumulative incidence of shunt stenosis or occlusion was 41.2% at 1 year and 54.9% at 2 years. Of those patients without shunt abnormalities after 1 year, 23.3% developed shunt stenosis or occlusion during the second year after TIPS procedure. Shunt revision was successful in 96.6% of cases. Secondary patency rate was 88.1% after 2 years. CONCLUSION: Successful TIPS implantation results in a low rate of morbidity and mortality from variceal rebleeding over 2 years. TIPS creation in combination with careful follow-up examinations represents an effective long-term treatment of recurrent variceal bleeding. Even in patients in whom no shunt abnormality is detected during the first year, routine duplex follow-up examinations should be continued at 3-month intervals.

Adult↗