High-dose interferon alpha-2a with ribavirin and amantadine in naïve chronic hepatitis C patients--results of a randomized, prospective, pilot study.

BACKGROUND: Hepatitis C viral kinetic studies have demonstrated the increased anti-viral effect of higher than standard dosages of interferon and of daily treatment schedules. AIM: To compare, in a prospective, randomized, controlled trial, the efficacy and safety of high-dose interferon-alpha therapy vs. standard-dosage interferon-alpha therapy, in a triple therapy combination with ribavirin and amantadine. METHODS: Previously untreated patients with chronic hepatitis C were randomized to the standard interferon-alpha group (n = 15), receiving thrice weekly 6 MU interferon-alpha for 12 weeks, followed by 3 MU interferon-alpha for 36 weeks, or the high-dose interferon-alpha group (n = 15), receiving daily 9 MU interferon-alpha for 4 weeks, followed by 6 MU (weeks 5-8), 3 MU (weeks 9-12) and 1.5 MU (weeks 13-48) interferon-alpha. All patients were given ribavirin (1000-1200 mg) and amantadine (200 mg) daily for 48 weeks. RESULTS: At the end of treatment and after the 24-week follow-up period, serum hepatitis C virus RNA was undetectable in eight (53%) and six (40%) patients treated with standard-dosage interferon-alpha, respectively, compared with 11 (73%) and 10 (67%) treated with high-dose interferon-alpha, respectively (not significant). The safety profile of both treatment regimens was similar. Severe adverse events leading to withdrawal from the study occurred in one patient (7%) in each group, and in both groups one patient (7%) was lost during therapy for unknown reasons. CONCLUSIONS: The findings suggest that, although the difference between the response rates of standard and high-dose interferon-alpha regimens (within a triple anti-viral therapy combination) did not reach statistical significance, there was a clear trend towards a higher response with high-dose interferon-alpha therapy and an equal safety profile.

[MARS (Molecular Adsorbent Recycling System) as a novel hepatic detoxification procedure until orthotopic liver transplantation]. / MARS (Molecular Adsorbent Recycling System) als neues Verfahren zum Ersatz der Leberentgiftungsfunktion bis zur orthotopen Lebertransplantation.

MARS (Molecular Adsorbent Recycling System) as a novel hepatic detoxification procedure until orthotopic liver transplantation. We report the case of a 30-year-old man who was admitted because of acute liver failure due to longstanding ethanol abuse. On conservative treatment liver function progressively deteriorated and the patient was listed for orthotopic liver transplantation. Because of a rapidly progressive and clinically severe hepatic encephalopathy together with increasing bilirubin levels (maximum 39 mg/dl) we began intermittent extracorporeal detoxification with the Molecular Adsorbent Recycling System (MARS). Under MARS therapy serum bilirubin decreased significantly (to 20 mg/dl after three cycles) and encephalopathy improved rapidly until the patient was completely oriented. No effect of MARS on liver function could be demonstrated. MARS treatment was successfully continued until a cadaver liver became available after 48 days and the patient was transplanted in good clinical and neurological condition and without complications. MARS represents a novel detoxification technique which, in patients with acute liver failure, can successfully replace hepatic detoxification until orthotopic liver transplantation can be performed.

Gastric wall elasticity assessed by dynamic holographic endoscopy: ex vivo investigations in the porcine stomach.

BACKGROUND: Holographic interferometry is based on the superimposition of the holograms of different motional states of an object on a single holographic storage medium. It has been used to detect structural changes in prosthetic heart valves. The combination of holographic interferometry and endoscopic imaging were applied to assess disturbances of porcine stomach wall elasticity. METHODS: By connecting an electronic speckle pattern interferometry (ESPI) camera system (light source: continuous wave argon-ion laser, lambda = 514.5 nm) to different types of endoscopes, ex vivo experiments were performed on porcine stomachs to detect areas characterized by altered tissue elasticity. With linkage of the endoscopic ESPI camera complex to a fast image processing system, the method of double pulse exposure image subtraction was applied at a video frame rate of 12.5 Hz. RESULTS: The speckle correlation patterns resulting from gentle gastric wall deformation were analyzed in a series of experiments in 16 porcine stomachs. Interferograms of gastric wall areas without structural abnormalities exhibited concentric fringes, whereas fringe patterns corresponding to areas of reduced tissue elasticity were characterized by parallel lines. CONCLUSION: Applying the nondestructive method of dynamic holographic endoscopy, abnormalities of the gastric wall leading to diminished tissue elasticity can be distinguished reliably from surrounding healthy tissue.

Helicobacter pylori-negative gastric ulcerations associated with celiac disease at first presentation.

Ulcers of the small bowel have repeatedly been described as a late complication of celiac disease and they are considered a signum mali ominis. We report a case of a 53-year-old woman presenting with diarrhea, epigastric pain and abdominal distensions for a period of few weeks. At upper GI endoscopy, biopsies were taken showing complete atrophy of the villi and colonization of the small bowel mucosa. Additionally, uncommon multilocular peptic ulcers were seen in the gastric antrum. These ulcers proved to be Helicobacter pylori-negative with no evidence of Zollinger-Ellison syndrome. Biopsies of gastric ulcers showed signs of a lymphocytic gastritis with an extensive infiltration of the lamina propria by almost exclusively CD3- and CD45R0-positive T-lymphocytes. Intraepithelial T-lymphocytes were found to be increased in the antral as well as the corpus mucosa. Typing the patient for human leukocyte antigens showed a DQA1*0501 and DQB1*0201 phenotype. According to the present report, gastric peptic ulcers seem to be another phenomenon associated with celiac disease. In the case presented here, ulcers were diagnosed together with celiac disease already at first presentation of the patient.

Endoscopic double-pulse electronic-speckle-pattern interferometer for technical and medical intracavity inspection.

An endoscope electronic-speckle-pattern interferometer (ESPI) camera system is presented that can be applied to examinations of technical objects as well as for in vitro and in vivo minimal invasive medical diagnostics. Integration of optical fibers for the guidance of a cw-laser beam and an endoscopic imaging system yield a compact ESPI system that opens up new possibilities for highly sensitive interferometric intracavity inspection under handheld conditions. A CCD camera in combination with a fast frame-grabber system allows dynamic image subtractions at a frequency rate of as much as 25 Hz with high fringe contrast. Results from investigations of technical objects and biological objects in vitro and in vivo are obtained. In endoscopic minimal invasive therapy this method could substitute for the missing operator's tactile contact with the treated tissue by replacing it with visual information (endoscopic taction).

Budd-Chiari syndrome in a patient with factor V Leiden--successful treatment by TIPSS placement followed by liver transplantation.

The causes of Budd-Chiari syndrome (BCS) comprise several diseases leading to thrombophilia. One of the most common thrombophilic disorders is resistance against activated protein C, caused by a single point mutation of the factor V gene. In December 1993, a 22-year-old patient was given a diagnosis of subacute BCS with occlusion of all major hepatic veins. Placement of a transjugular intrahepatic portosystemic stent shunt led to rapid disappearance of ascites and hepatic encephalopathy. During the following two years, recurrent partial occlusions of the shunt were treated by balloon angioplasty. The cause of the BCS still being unknown, in October 1996 we performed extensive laboratory investigations concerning states of thrombophilia and found moderately elevated IgG anticardiolipin antibodies (19.7 U/ml) and a resistance against activated protein C caused by heterozygosity for a point mutation of the factor V gene (1691G-->A; factor V Leiden). As a consequence, oral anticoagulation with coumarin was initiated. In October 1997, elective liver transplantation was performed which led to disappearance of APC resistance. Moreover, IgG anticardiolipin antibodies have been negative since then. If BCS is caused by APC resistance, liver transplantation not only treats the chronic liver disease but also cures the state of thrombophilia since factor V is mainly synthesized in the liver.

Metastatic pancreatic VIPoma: deteriorating clinical course and successful treatment by liver transplantation.

Gastrointestinal neuroendocrine tumors are slowly growing and metastases are often limited to the liver. As a result of their favorable biological behavior these tumors have a relatively good prognosis even in metastatic stage. Due to a variety of therapeutic options patients with malignant neuroendocrine tumors may survive for extended periods of time up to ten years. Often a combination of different treatments and also alternation between the different therapeutic regimes is needed. A patient with excessive WDHA-syndrome and severe metabolic disturbances due to a pancreatic VIPoma with metastatic spread into the liver and abundant hormonal secretion is presented. Cytotoxic agents (streptozocin, 5-fluorouracil and adriamycin) were able to alleviate clinical symptoms and to control tumor growth for six years. Analogues of somatostatin (octreotide) and interferon alpha had been very useful in controlling clinical symptoms and tumor progress for 18 months. Cytotoxic agents or octreotide were not able, however, to achieve any permanent cure. Eventually, treatment failure occurred with dramatic progression of symptoms and tumor growth, unresponsive to any medical therapy. Consequently, total hepatectomy and liver transplantation together with extirpation of the pancreatic primary tumor was performed and succeeded in providing a normal life to the patient. In our opinion the overall outcome of patients with metastatic VIPoma may be improved best by maintaining the patients on medical therapy until treatment failure occurs. In case of extended hepatic metastases orthotopic liver transplantation might be considered for patients with symptomatic disease who no longer respond to conventional treatment modalities.

Injection of fibrin tissue adhesive versus laser photocoagulation in the treatment of high-risk bleeding peptic ulcers: a controlled randomized study.

BACKGROUND AND STUDY AIMS: A controlled and randomized multicenter study was carried out in order to compare the efficacy of fibrin sealant and Nd:YAG laser photocoagulation in patients with high-risk arterial bleeding from peptic ulcers of the stomach and the small intestine. PATIENTS AND METHODS: In four teaching hospitals, 53 patients presenting with either active arterial ulcer bleeding (Forrest class 1 a) or a large visible vessel in the ulcer base (diameter over 2 mm, Forrest class 2 a) were treated with infiltration of epinephrine 1: 10,000 followed by the injection of fibrin tissue adhesive (n = 28), or with epinephrine plus laser photocoagulation (n = 25). Permanent hemostasis for at least seven days served as the principal end point; rebleeding, emergency surgery, and hospital mortality served as further end points. RESULTS: There were no significant differences between the study groups in terms of age, risk factors, initial hemoglobin values, number of patients showing signs of hemodynamic impairment, ulcer size and localization, or bleeding activity. Primary hemostasis was achieved in all patients. Rebleeding rates were seven of 28 and four of 25 among the patients treated with fibrin sealant and laser coagulation, respectively (not significant). There were no significant differences regarding the rates of ultimate hemostasis (24 of 28 vs. 24 of 25), emergency surgery (four of 28 vs. one of 25), or hospital mortality (0 vs. two of 25). No complications occurred with either form of treatment. Patients who had a visible vessel in the ulcer floor at the first control endoscopy had a significantly higher incidence of rebleeding, regardless of the type of endoscopic therapy. CONCLUSIONS: We conclude that both the injection of fibrin tissue adhesive and laser photocoagulation are effective methods of treating high-risk arterial peptic ulcer bleeding. As the number of high-risk patients necessary to reach significance are difficult to recruit within a reasonable period even in a multicenter study, a new meta-analysis of all studies now available should be considered.