Ablation of Barrett's epithelium by endoscopic argon plasma coagulation in combination with high-dose omeprazole.

BACKGROUND: Barrett's esophagus is a premalignant condition induced by gastroesophageal reflux. The aim of this prospective study was to assess the efficacy of argon plasma coagulation in combination with high-dose omeprazole therapy to ablate nondysplastic Barrett's epithelium. METHODS: In 73 patients with histologically confirmed Barrett's epithelium, argon plasma coagulation was used in combination with maximal acid suppression (omeprazole 40 mg three times a day). Histologic and endoscopic changes were evaluated at 6- and 12-month intervals. RESULTS: In 69 of 70 patients (98.6%) complete squamous regeneration was achieved after a median of 2 argon plasma coagulation sessions (range 1 to 5). During a median follow-up of 12 months (range 2 to 51 months) there has been no relapse or evidence of the development of dysplasia under continuous acid suppression. Three patients (4.3%) developed a mild stricture of the distal esophagus that resolved after a single session of bougie dilation. CONCLUSIONS: In our experience, argon plasma coagulation in combination with high-dose omeprazole treatment is an effective and safe technique for complete ablation of nondysplastic Barrett's epithelium. Restoration of squamous mucosa after argon plasma coagulation appears to be long-lasting.

Spontaneous regression of hepatocellular carcinoma confirmed by surgical specimen: report of two cases and review of the literature.

Two cases with spontaneous regression of a histologically confirmed hepatocellular carcinoma (HCC) are presented. This rarely seen phenomenon of a spontaneous tumor involution is discussed and compared with the current literature. The clinical symptoms were very similar to that of a liver abscess. A 56-year-old male suffered from a multicentric, highly differentiated, trabecular HCC. First symptoms were epigastric pain, septic fever and arthritis. The tumor marker AFP was constantly normal and no hepatitis could be verified. A resection of the tumor was performed. In patient 2, a 74-year-old male, a multicentric, clear cell HCC was found. The patient had completely recovered from hepatitis type B and within the liver tissue no viruses could be identified. Clinical symptoms were mainly characterized by upper abdominal pain and septic fever. AFP was excessively elevated (3850 ng/ml) but returned to normal preoperatively. In both cases, the specimen showed a subtotal necrotic HCC with insignificant amounts of vital tumor cells. Neither patient had a liver cirrhosis macroscopically, however patient 2 had local periportal fibrosis histologically. After 24 and 41 months of follow-up, respectively, both patients are in good health

Very fast ultracentrifugation of serum lipoproteins: influence on lipoprotein separation and composition.

A very short run time and small sample volumes in the separation of lipoproteins by preparative ultracentrifugation are needed for several investigations. Recently, a very fast sequential separation method was described that needs only 100 min for one run in a centrifugal field of 625,000 x g. We studied the influence of centrifugal fields of this dimension on lipoprotein separation and lipoprotein particle integrity using a Beckman Optima TLX ultracentrifuge with a TLA-120.2 rotor. Rotor speed (120/90/60/30.10(3) rev./min) and run time (100 min/3 h/6.7 h/27 h) were selected in such a way that the product of centrifugal field and run time remained constant. The first conditions correspond to the very fast ultracentrifugation (VFU) procedure with a centrifugal field of 625,000 x g. Thirty different plasma samples covering a wide range of lipid and protein concentrations were separated in the course of two centrifugal runs at densities of 1.006 and 1.063 kg/l which yielded very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and the subnatant of low-density lipoproteins, including high-density lipoproteins (HDL) and concomitant sedimented plasma proteins. The major lipid components of the lipoproteins, triacylglycerols, free and esterified cholesterol, phospholipids and the apolipoproteins B and A-I, were estimated considering the masses of the tube contents after a slicing procedure. Measurements of lipids and proteins showed a very good recovery of better than 94% and 91%, respectively, and precision-within-series (coefficient of variation) of better than 4.2% and 6.5%, respectively. The effects of the rotor speed on the lipoprotein structure appeared to be weak. With increasing rotor speed, VLDL and LDL lipid constituents principally tended to decrease, whereas they increased in the subnatant of the LDL-run. The mean lipoprotein mass composition, considering the mass percentage of each measured particle constituent, did not show significant alterations. Total protein decreased in VLDL and in LDL and increased in the subnatant of the LDL-run. As checked by an enzyme-linked immunosorbent assay (ELISA) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), the protein effects were due to nearly complete disappearance of contaminating plasma proteins, especially albumin as the major contamination of VLDL and LDL. The apolipoproteins (apo) B-100, A-I, E and C-I to C-III remained nearly unaffected. The main advantages of VFU were the very short run time (cumulative flotation time is 3.4 h) and the elemination of albumin without repeated runs. The procedure was suitable for the assessment of lipid and protein constituents in lipoproteins from very small plasma samples (500 microliters).

[Reversible thrombocytopenia due to digitoxin overdose]. / Reversible Thrombozytopenie bei Digitoxinüberdosierung.

A 65-year-old woman, known to have peptic ulcers, developed nausea and retching. Clinical examination demonstrated pain on pressure in the epigastrium with otherwise normative findings for age. Two gastric ulcers and gastritis with erosions were seen at endoscopy. The patient, who was being treated with digitoxin for heart failure, reported having taken up to four digitoxin tablets (0.07 mg each) daily because she had insomnia. The plasma digitoxin level was between 150 and 160 nmol/l (therapeutic range 17-33 nmol/l), while the ECG showed no signs of digitalis intoxication. Initially the platelet count was 40,000/microliter: there had been no history of thrombocytopenia or symptoms of abnormal haemostasis. Other laboratory tests were within normal limits. After digitoxin had been discontinued, the platelet count rose without further treatment to 373,000/microliter 3 weeks after hospital admission by which time the digitoxin level had fallen to 48.9 nmol/l. The gastrointestinal symptoms regressed completely on treatment with omeprazole (40 mg three times daily for 8 days) and ranitidine (150 mg twice daily).

Immunomodulating effect of ursodeoxycholic acid therapy in patients with primary biliary cirrhosis.

Peripheral blood lymphocytes of 22 patients with primary biliary cirrhosis under ursodeoxycholic acid therapy were examined for selected lymphocyte activation markers. The percentage of dipeptidyl peptidase IV positive Peripheral blood lymphocytes of primary biliary cirrhosis patients by using immune- and enzyme-histochemical staining was found to be low (5-12%), with healthy controls exhibiting a normal range of 18-27%. After pokeweed mitogen stimulation in vitro the interleukin-2 production by peripheral blood lymphocytes in primary biliary cirrhosis patients was significantly decreased (3.135 pg/ml mean value), compared to healthy subjects (61.167 pg/ml mean value). After 4-20 weeks ursodeoxycholic acid treatment the dipeptidyl peptidase IV expression and IL-2 production were normalised. These results provide evidence for the immunomodulating effect of ursodeoxycholic acid.

[Dipeptidyl peptidase IV of peripheral blood lymphocytes in patients with primary biliary cirrhosis]. / Untersuchungen der Dipeptidyl-Peptidase IV peripherer Blutlymphozyten bei Patienten mit primärer biliärer Zirrhose.

Investigations concerning changes of dipeptidyl-peptidase IV-positive (DP IV+) lymphocytes in the peripheral blood (PBL) were undertaken in 22 patients with primary biliary cirrhosis (PBC) under therapy with ursodeoxycholic acid (750 mg/day). We found that after 4-8 weeks of therapy the number of DP IV+ PBL was raised from an initially low, suppressed level of 5-12% to 18-33% corresponding to the range observed in healthy subjects. Concurrently liver function parameters of the patients were significantly improved. The identity of DP IV+ CD 26+ peripheral T-cells could be shown by the combination of cytochemical DP IV-staining with the indirect immuno-fluorescence of the lymphocyte marker CD 26. These results show that the UDCA-therapy in patients with PBC has a direct effect on the immune system and a positive influence on the immuno-regulative capacity.

[Dipeptidyl-peptidase IV of human lymphocytes in patients with primary biliary cirrhosis and UDCA therapy]. / Dipeptidyl-peptidase IV humaner Lymphozyten bei Patienten mit primärer biliärer Zirrhose unter UDCA-Therapie.

Investigations concerning changes of dipeptidyl-peptidase IV-positive (DP IV+) lymphocytes in the peripheral blood (PBL) were undertaken in 22 patients with primary biliary cirrhosis (PBC) under therapy with ursodeoxycholic acid (750 mg/day). We found that 4-8 weeks after therapy beginning the number of DP IV+ PBL was raised from a low initial suppressed level of 5-12% into a range of 18-33% corresponding to that of a healthy. Concurrently liver function parameters of the patients were improved significantly. The identity of DP IV+ and CDw26+ of peripheral T-cells could be shown by combination of the cytochemical DP IV-staining with the indirect immunofluorescence of the lymphocyte marker CDw26. These results show that the UDCA-therapy in patients with PBC has a direct effect on the immune system and a positive influence on the immuno-regulative capacity.

[Endoscopy in cholestasis]. / Endoskopie bei Cholestase.

The spectrum of causes of cholestasis ranges from microscopically recognizable damage to the parenchymal cells of the liver to obstruction of the ductus choledochus und papilla Vateri. Liver biopsy on the one hand and ERCP on the other therefore constitute the morphological methods that come closest to the pathological substrate. Obligatory sonography serves the restriction of diagnosis to a large extent. Laparoscopy is nearly always dispensable. Even in case of liver biopsy the therapeutic consequences should have an influence. Consequently, for transpapillary endoscopic methods in obstructive jaundice it is essential to remove the obstruction (papillotomy and extraction of the calculus or nasobiliary probe or intraluminal tube) if possible in one and the same session. The purely diagnostic ERC possibly causes dangerous cholangitis in mechanical icterus. Transpapillary and percutaneous transhepatic endoscopic methods are becoming more and more sophisticated and new indications are being discovered. However, the results of sonography and endoscopy in obstructive jaundice depend very much on the equipment available and experience of the investigator. He should realistically estimate what he is able to do as well as the patients' chances of recovery. In addition he should maintain contact to large departments of surgery and endoscopy.

[The significance of internal medicine intensive care within the complex of intensive medicine. Discussion contribution to the structural and professional classification in adult intensive medicine]. / Stellenwert der internistischen Intensivbehandlung im Komplex der Intensivmedizin. Diskussionbeitrag zur strukturellen und fachlichen Gliederung in der Erwachsenenintensivmedizin.

The development and establishment of intensive care units for adult patients requires a far-reaching subdivision into surgical and conservatively oriented intensive care for qualitative and quantitative reasons. Insufficiently substantiated claims to monopolization of intensive care techniques that are polemically asserted have to be strongly contradicted. The present paper is concerned with approved structural concepts of intensive care developed by Deutsche Krankenhausgesellschaft and various medical societies. They are supplemented by personal experience in the field of internal intensive care.

[Lipid metabolism disorders in primary biliary cirrhosis (PBC)]. / Fettstoffwechselstörungen bei primär biliärer Zirrhose (PBC).

40 women, average age 52.5 years, with varying stages of primary biliary cirrhosis, were observed. One third of them suffered from a mild anaemia, mean plasma concentrations of ALAT were increased four times and those of AP six times. Despite the hepatocellular damage products of the liver synthesis such as transport proteins or coagulation factors were found to be normal or enhanced. 60% of the patients had a hypercholesterolaemia. The risk factors low density lipoprotein (LDL)- and very low density lipoprotein (VLDL)-cholesterol showed normal levels, but the protective factor high density lipoprotein (HDL)-cholesterol was clearly increased. Apart from the low blood pressure in most of the patients and the absence of other risk factors these observations explain, why patients with PBC and hypercholesterolaemia don't usually develop arteriosclerotic complications. Only in case of severe cholestasis a lipid constellation comes into being accompanied by high risk for the blood vessels, but in these cases the terminal stage of PBC limits the survival. Positive correlations between markers of cholestasis and lipid parameters let an enhanced production and simultaneous impaired excretion of cholesterol be assumed.

[The effect of various non-ulcer pharmaceuticals on nocturnal gastric pH in healthy subjects]. / Die Wirkung verschiedener Nichtulkuspharmaka auf den nächtlichen Magen-pH gesunder Probanden.

The effects of 4 non-ulcer drugs and the M1-antagonist pirenzepine on the nocturnal intragastric pH were investigated in 12 healthy volunteers. We tested single doses of pirenzepine (100 mg), Chlorprothixene (30 mg), clonidine (75 micrograms), ketotifen (3 mg) and nifedipine (30 mg) in an randomized, single-blind, cross-over study. The nocturnal intraluminal pH is significantly elevated not only by pirenzepine but also by the other substances. As expected pirenzepine (mean nocturnal pH = 2.49 +/- 0.22) shows the most distinct effect, nifedipine (mean nocturnal pH = 1.72 +/- 0.20) the most sparsely effect. The other drugs are nearly half as effective as pirenzepine. The acid suppressive side effect of the non-ulcer remedies is considered to be important for the treatment of ulcer patients with concomitant diseases.

[Ultrasonography studies on spontaneous and pharmacologically modified gallbladder motility]. / Sonographische Untersuchungen zur spontanen und medikamentös beeinflussten Gallenblasenmotilität.

The intra- and interindividual variations of gallbladder motility were sonographically studied in 10 healthy subjects. We investigated the following criteria: a) the gallbladder volumes after overnight fasting on 5 consecutive days, b) the spontaneous motility under fasting over 12 or 24h at hourly intervals, c) the emptying rate and time of maximal contraction after stimulation with sorbitol, and d) the emptying rate and time (like c) after premedication with "cholagogic" drugs (Cholecysmon, Divalol), nifedipine, indomethacin or N-butylscopolaminiumbromide. We found a great intrapersonal and interpersonal variability in gallbladder volumes after overnight fasting in consecutive days. In subjects fasting over 24h phases of dilatation with maxima at 12 AM and 4 PM alternated with phases of contraction with maxima at 8 AM and 4 PM. After premedication with nifedipine, indomethacin and N-butylscopolaminiumbromide a significant decrease of the emptying rate was observed. The time of maximal contraction did not differ however. After premedication we found a distinct intra- and interindividual variability too. Cautious interpretation of gallbladder motility studies is necessary.

Prophylactic endoscopic sclerotherapy of esophageal varices--a prospective randomized trial.

Sixty-three patients with degree III or IV esophageal varices and the so-called red color sign, but without previous bleeding were randomly assigned to either prophylactic sclerotherapy (PST) (n = 30) or to a control group (n = 33). In 58 cases the portal hypertension was caused by liver cirrhosis (40% alcoholics). The two groups were comparable with respect to demographic data and endoscopic appearance, causes and severity of liver damage. Sclerotherapy was performed as combined intra-and paravariceal injections of 2 or 3% polidocanol. All patients, both in the treatment and in the control groups, who bled from varices after randomization, received sclerotherapy until the varices were eradicated, and remained in their groups. After a mean follow-up of 44.5 months, the bleeding rate in the PST group was significantly lower (30% vs 75%, p less than 0.01). The difference became significant from the second year onward. Fourteen patients of the PST group and 19 of the controls died (4 and 14, respectively, p less than 0.05 as a result of the bleeding). Life table analysis (Kaplan-Meier) revealed no differences in survival between the two groups. At the present time PST cannot yet be recommended as a method for clinical routine use.

[Drug-induced liver damage from the clinical viewpoint]. / Medikamentöse Leberschäden aus klinischer Sicht.

Extensive drug-induced hepatic injury leading up to jaundice occurs relatively rarely. Generally it is not predictable, independent on dosage and irreproductible in animals. As a rule you find it in less than 0.1% of the patients taking the drug, whereas the degree may range up to heavy or lethal (e.g. for isoniazid, methyldopa, halothane). Pathogenetically reactive metabolites capable of producing cytotoxic and/or immune reactions may play a role. Obviously higher age, female sex and endogenous or exogenous alterations in hepatocellular drug metabolism are disposing factors. Drugs, to which our patients most frequently reacted, were dihydralazine alone or in combination with propranolol, and ketophenylbutazone. The lymphocyte transformation test proved diagnostically valuable although it cannot be considered to represent a generally reliable testing method for drug-induced liver disease. Clinical, laboratory and histological findings are typical with a wider range of drugs, but liver biopsy provides the most reliable criteria. Clinical suspicion and stopping the intake of potentially noxious drugs are of importance. The reexposition test should be reserved to exceptional cases.