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Biomedical subjects

U Leuschner

Publications and source records attributed to U Leuschner.

At least 19 recordsLinked to original sources

[Comparative study of superoxide production of monocytes in primary biliary cirrhosis].

Monocytes appear to play a role in immunological abnormalities observed in primary biliary cirrhosis (PBC). Monocytes not only produce fibroproliferative factors, such as IL-1, TNF, and PDGF but also produce superoxide anion which can directly damage tissues, and thus may lead to fibrosis. The aim of this study was to compare the superoxide production in monocytes obtained from 12 control persons, 9 patients with non biliary cirrhosis, 6 untreated PBC patients, 6 patients with gallstones under urso- and chenodeoxycholicacid (Lithofalk) treatment and 32 PBC patients under ursodeoxycholicacid (UDCA) therapy. Monocytes were isolated and the production of superoxide anions with and without phorbol-myristate-acetate (PMA) stimulation was determined. In two occasion, the monocytes from control patients were preincubated with 10, 50, 100 microM UDCA. Unstimulated monocytes from PBC patients under UDCA therapy produce an average 43% more and the PMA stimulated monocytes an average 42% more superoxide than monocytes from the control or from the other cirrhotic patients. The UDCA preincubation did not influence the superoxide production of monocytes obtained from control patients. These findings suggest that the increased activity of monocytes may also play a role in liver damage and fibrosis in PBC.

Anions

[Drug therapy of cholestatic hepatopathies].

Ursodeoxycholic acid is suitable for the treatment of primary biliary cirrhosis and primary sclerosing cholangitis in a dosage of 10 mg/kg bodyweight per day. In primary biliary cirrhosis not only laboratory parameters but the histological picture as well are markedly improved. Best results are obtained in the early stages of the disease (stage I, II), but there is an improvement in the late stages (stage III, IV) too. A long-term follow-up has shown that bile salt therapy is possible without any side effects and with excellent results during a period of 10 years. Excellent results have been obtained in newborns with primary bile duct atresia and in patients with cystic fibrosis.

Cholangitis, Sclerosing

[Drug therapy of gallstone disease].

Cholesterol stones in the gallbladder can be dissolved in 60 to 90% by oral administration of chenodeoxycholic acid, ursodeoxycholic acid or the combination of both. The effect depend on the number and size of stones. Treatment is without any side effects and lethality. A great number and large stones can be dissolved by direct instillation of methyl-tert-butyl-ether (MTBE) into the gallbladder using the percutaneous transhepatic method. The success rate amounts to 90%, the average therapy duration is 9 hours. Solvents for chemolitholysis of pigmented stones are being tested.

Chenodeoxycholic Acid

Experimental dissolution of pigment gallstone material using alkaline EDTA and adjuvant bile salts/non-bile salt detergents, thiols and urea, with respect to local chemolitholysis.

In order to enhance the dissolution capacity and the kinetics of topical solvents used in local pigment chemolitholysis, a series of dissolution experiments was performed with intact brown and black pigment stones and with standardized solutes such as pigment stone powder and compressed powder (static disc method). The basic dissolution medium was a 0.1 M boric acid/sodium carbonate buffer (pH 9.5), and the basic lytic agent was EDTA-4Na, working satisfactorily at 1-3 g/dl. It could be demonstrated that the dissolution efficiency of this basic solvent was enhanced significantly in the presence of a detergent (surfacant) and of urea. Among the detergents the zwitterionic (e.g., Sulfobetain-12) and the nonionic types (e.g., a polyoxyethylene ether like Lubrol PX) proved to be most effective. The adjuvant effect of the investigated thiols was disappointing. Only dithioerythritol/dithiothreitol and N-acetylcysteine showed any moderate, if consistent, lytic activity. The highest dissolution rates in dissolving compressed powder standards (disc method) were achieved with the ternary solvent (1% w/v EDTA/80 mM Lubrol PX/1 M urea, pH 9.5). Intact black pigment stones, well known as problematic candidates for chemolitholysis, could be largely dissolved up to approximately 70% of their initial weight. This was not merely a physical disintegration, but a chemical process.

Buffers

Mucin-like high molecular mass protein fractions from total pig gallbladder bile mucus, pig gallbladder wall mucus, and total human gallbladder bile mucus.

Native mucin-like complexes were obtained from both pig gallbladder bile and pig gallbladder wall mucus by precipitation, centrifugation, and gel permeation chromatography. Crude preparations by either dialysis (native mucus from bile, and native gallbladder wall mucus) or by precipitation (crude total bile mucus, and lipomucoid) were purified by gel permeation chromatography on Sephacryl S-300HR and Sephacryl S-500HR (Pharmacia). The elution profiles obtained with a reversibly denaturing and detergent-containing eluent showed the same pattern for all samples, although the amounts of the four main fractions differed somewhat. The excluded fraction with the highest carbohydrate portion had an apparent M(r) > 10(7). This fraction and the following included lipomucoid (in physiological solution tightly bound to fraction I), and an eluent-insoluble mucus portion from all samples were characterized by determination of the protein concentration, carbohydrates, sialic acids, and lipids, using standard methods. Sugar analysis was performed by gas-liquid chromatography. Human gallbladder bile was subjected to the same procedures of mucus precipitation and separation. Human gallbladder bile mucus showed identical behaviour to that of pig gallbladder bile mucus, and showed a very similar elution pattern in gel chromatography.

Animals

Treatment of chronic active hepatitis and primary biliary cirrhosis with ursodeoxycholic acid.

Ursodeoxycholic acid (UDCA) improves liver function tests in patients with chronic active hepatitis (CAH) and primary biliary cirrhosis (PBC). UDCA will reduce biochemical parameters of both cholestasis and hepatocellular damage. The effects may be less beneficial in patients with advanced stages of chronic liver disease: in PBC we found the improvement of laboratory parameters in stage I and II very impressive, in stage III and IV it was less marked. Data of two controlled trials in PBC showed an improvement in liver histology, in one study the improvement was statistically significant. UDCA can be administered for at least 10 years without any adverse effects, the treatment is safe and improves life quality. The mode of action of UDCA seems to be in its displacement of toxic hydrophobic bile salts from the bile acid pool and the hepatocellular membrane. In in-vitro investigations a direct protective effect of UDCA on isolated sinusoidal hepatocyte membranes against toxic bile salts has been shown. This protective effect of a more general nature may explain the efficacy of UDCA in different chronic, especially cholestatic liver diseases.

Adult

[Endoscopy, shockwave lithotripsy and local lysis in complicated pigmentary calculi of extra- and intrahepatic bile ducts].

Endoscopy, extracorporeal shockwave lithotripsy (ESWL) and local lysis with alkaline solution of EDTA and bile salts in water were applied in combination in four patients with extra- and intrahepatic pigment stones as well as calcium bilirubinate covered concrements of the biliary tract. In the first patient (a man aged 80 years) a giant concrement of the bile duct was broken up after ESWL by three weeks of local chemical lysis and the fragments were removed by endoscopy. In the second case (man, aged 72), a nonextractable pigment stone was at first reduced in size by four-day local lysis and then removed endoscopically. Intrahepatic pigment stones were completely removed in the other two patients (boy of 12, man of 62) by local lysis only in 3 and 15 weeks, respectively. Even long-term use of the alkaline solution may not cause any serious side effects. Breaking up of stones after size reduction with ESWL of giant stones, size reduction of intact stones and contact lysis of intrahepatic stones are three important indications for chemical dissolution of biliary tract stones, respectively.

Adolescent

Gallstone dissolution with methyl tert-butyl ether in 120 patients--efficacy and safety.

Of 612 patients with cholesterol gallbladder stones, 120 were eligible for percutaneous transhepatic litholysis with methyl tert-butyl ether (MTBE). Puncture of the gallbladder was successful in 117/120 (97.5%). In 113/117 (96.6%) the stones dissolved. With solitary stones, treatment lasted for an average of 4 hr, with multiple stones 10 hr. Mean hospitalization was 3.6 days. In 3/117 (2.6%) patients a bile leakage developed; 33% reported mild complaints. After the end of treatment 34% had some residue in the gallbladder; two of these patients developed recurrent stones. MTBE is exhaled, is distributed in fatty tissue, and is excreted renally together with its metabolite tert-butanol. Methanol was found only in traces. Gallbladder histology of six patients showed chronic cholecystitis. Since these findings were independent of treatment time and the interval between treatment end and operation, they are most consistent with stone-related changes rather than caused by MTBE.

Adult

[The effect of pH and amount of antacids on bile acid binding in a quasi-natural reflux milieu].

Bile acid adsorption may be one therapeutical mechanism of antacids. Little is known about the effect of pH and amount of antacid on bile acid adsorption. Therefore we carried out the following investigations using a lattice [correction of lettuce] layer antacid as a model substance. 5 ml of "quasi-natural reflux milieu" were mixed with 0.5, 1 or 2 ml of hydrotalcite and adjusted to pH 3, 5 or 7. The highest total bile acid adsorption was found at pH 3, the degree of bile acid adsorption correlated with bile acid lipophilicity, i.e. the most lipophilic and toxic bile acids are adsorbed best. High adsorption of lipophilic and particularly toxic bile acids even at low gastric pH may help to explain the good therapeutic effect of low-dose antacids in gastric ulcer.

Adsorption

Percutaneous transhepatic gallstone dissolution with methyl tert-butyl ether in complicated stone diagnosis and gallbladder anomalies.

In a total of 117 successfully punctured patients with gallbladder stones that were to be treated with methyl tert-butyl ether, 11 showed shell-like structured concrements on the CT scan. In 2 patients, pigment stones and very old concrements were suspected. In these 13 patients solitary stones dissolved in 2.9 hours, multiple stones in 10.8 hours, which corresponds to the treatment time of the total group. In 4 patients we diagnosed cholesterol stones, but dissolution was very slow, suggesting that the stones were covered with pigment. In 21 patients we found marked gallbladder anomalies, such as extreme septation, two-chamber gallbladders, gallbladder diverticula with a wedged stone, or gallbladders in which the fundus was positioned cranially. In these patients puncture time was prolonged by 25%. However, since in all patients the stones dissolved in the same time as in the total group (solitary stones; 3.1 hours: multiple stones: 10.4 hours) and since in 33% there was also sludge in the gallbladder, shape variants of the gallbladder obviously have no influence on the stone type. Whether they induce recurrent stones more often than normal gallbladders cannot be assessed at present. Shape variants of the gallbladder and layered stones on CT scan, however, do not represent a contraindication to MTBE therapy.

Cholecystography

Gall stone dissolution with methyl tert-butyl ether: how to avoid complications.

Fifty of 52 patients with cholesterol gall bladder stones were treated with methyl tert-butyl ether. In 48 of 50 (96%) patients the stones dissolved after an average interval of 9.5 hours. Mean stone size was 1.7 cm (0.5-3.3 cm), mean stone number was 14.6 (1-70). Twelve patients (24%) complained of nausea, a burning sensation, or vomiting. In one patient bile leakage occurred and another suffered haematobilia (4%). The puncture set was improved, and a special basket was developed to extract stones that had escaped into the cystic duct. To prevent bile leakage or haemorrhage from the incision channel, a tissue adhesive was injected into the channel or ceruletid was administered subcutaneously before removing the catheter to induce contraction of the gall bladder. Thus we were able to treat 44 patients without any complications. Nausea and vomiting could be reduced if the treatment time was kept short and the perfusion volume was as low as possible. Methyl tert-butyl ether treatment is a successful treatment of gall bladder stones with few complications.

Adult