[The diagnosis of intrahepatic cholestasis].
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Biomedical subjects
Publications and source records attributed to W Kurtz.
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Bile acids are a factor in the pathogenesis of peptic lesions of the mucosa. The introduction in the literature of the term type C gastritis reflects the recognition of this fact. It is possible that antacids develop their effect not merely via the neutralization of hydrochloric acid, but, to an appreciable extent, through the adsorption of toxic substances. Since antacids often elevate the gastric pH only slightly, we investigated bile acid binding not only as a function of dose, but also at low pH values. The aim of the study was, in a follow-on to previous studies of a layer-lattice antacid to describe the characteristics of an antacid of the mixed type (aluminium-magnesium hydroxide + smectite). Already at neutral pH, Gelofalk manifests a high level of bile acid absorption, which increases further at low pH values. The high bile acid absorption capacity of Gelofalk shows no correlation with decreasing bile acid polarity; the dose-dependency is lower at high than at low pH levels. This indicates that bile acid absorption by Gelofalk must, at least in part, involve other mechanisms than those operative in the case of pure layer-lattice antacids.
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.
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.
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Non-surgical treatment of cholesterol gallstones is possible with oral chemolitholysis employing chenodeoxycholic acid (CDA) and/or ursodeoxycholic acid (UDA), oral chemolitholysis following ESWL and direct dissolution with methyl tert-butyl ether (MTBE). Oral chemolitholysis takes a long time (6-24 months), is suitable only for small stones (up to 1.5 cm) and has a success rate of 60-70%. Prior ESWL shortens the duration of oral treatment moderately and can be employed with larger (up to 3 cm) stones; it is, however, quite expensive. The new method of direct chemolysis of gallstones is rapid, very cheap, and effective (approx. 95% success rate), but is an invasive procedure. If previous results obtained with MTBE are confirmed, it could become a therapeutic alternative to cholecystectomy in the case of very large and multiple stones.
The effects of pulsed electromagnetic fields (PEMF) on rat sciatic nerve regeneration after a crush lesion were determined. The rats were placed between a pair of Helmholtz coils and exposed to PEMF of frequency 2 Hz and magnetic flux density of 0.3 mT. A 4 h/day treatment for 3-6 days increased the rate of nerve regeneration by 22%. This stimulatory effect was independent of the orientation of the coils. Exposure times of 1 h/day-10 h/day were equally effective in stimulating nerve regeneration. Rats exposed to PEMF for 4 h/day for 7 days before crush, followed by 3 days after crush without PEMF, also showed significantly increased regeneration. This pre-exposure 'conditioning' effect suggests that PEMF influences regeneration indirectly.
We studied the effect of ursodeoxycholic acid on 18 women and 2 men with primary biliary cirrhosis, mainly stages I and II. After a 3-mo observation period, patients were randomized to a 9-mo treatment period with ursodeoxycholic acid, 10 mg/kg.day, or placebo. Two patients on placebo left the study. In all patients on ursodeoxycholic acid, mean values of serum glutamate dehydrogenase, aspartate and alanine aminotransferases, alkaline phosphatase, and gamma-glutamyl transpeptidase fell significantly by 48%-79% after 18-24 wk; 7 of 10 showed a mean decrease of 35% in immunoglobulin M after 24 wk. Prothrombin time, serum bilirubin, albumin, the antipyrin breath test, and plasma disappearance of indocyanine green were normal initially and did not change. Total serum bile acid concentrations increased; ursodeoxycholic acid became the predominant bile acid. No significant improvement occurred in the placebo group. Hepatic histology improved in 6 patients of the ursodeoxycholic acid group but deteriorated in 4 patients receiving placebo. In studies with erythrocyte membranes, changes in electron spin resonance revealed that ursodeoxycholic acid was less toxic than chenodeoxycholic or deoxycholic acid, and coaddition of ursodeoxycholic acid prevented their toxic effect.
In a "quasi-physiological" reflux mixture obtained from non-stimulated gastric juice and hepatic bile the bile acid adsorption of 7 antacids is investigated with an newly developed HPLC method. The antacids produce pH values varying from 3.7 to 7.6. With increasing pH and increasing polarity of bile acids the bile acid binding to antacids decreases. The theoretically desirable combination of high pH and good bile acid binding is difficult to achieve. The relatively good total bile acid binding (over 60%) by Trigastril at a high pH (7.53) contrast with better bile acid adsorption by Maaloxan and Aludrox (about 90%) at a lower pH (4.5-4.9). Interestingly, toxic nonpolar bile acids are particularly well adsorbed by antacids.
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In 15 patients (13 women and two men) with cholesterol stones in the gall-bladder a special (Thistle) catheter was introduced into the gall-bladder under local anaesthesia by percutaneous transhepatic puncture. Methyl-tert-butyl ether, 2-15 ml, was injected via the catheter and removed again after 2 min. The number of stones per gall-bladder averaged 6.3 (1-20), size of stones 1.7 cm (0.5-2.8 cm), and duration of treatment 11.9 h (5-24 h). The stones dissolved in 13 patients (87%). In three patients stone débris remained: in one it was ultimately sucked out after reduction of the amount of débris with an EDTA-containing solution. The side effects of treatment--nausea and vomiting--were minor. In one patient there was a leak of bile from the gall-bladder after the procedure; a cholecystectomy was uneventfully performed. Another patient developed haemobilia which responded to conservative treatment. MTBE treatment has thus proved to be a successful and cheap method, low in side effects, in the treatment of patients with gall-stones.
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In a controlled prospective double blind trial patients with cholesterol gall bladder stones are treated with ursodeoxy-cholic acid (group A: UDCA 11.1 mg/kg per day; n = 16) and Ursomenth respectively (group B: a mixture of UDCA/menthol: 4.75 mg/kg per day each; n = 17). With same stone number and size (10-12 mm) there is a complete dissolution rate in group A of 38%, and of 53% in group B within 15-16.9 months. The response rate (complete + partial dissolution) amounted to 75% and 76% respectively. In group A there is one case of stone calcification, in group B none. Both preparations are free of unwanted effects. This suggests that the cyclic monoterpene menthol enhances the effect of UDCA and is of comparable effect to a mixture of six different terpenes used in former times.
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We report on a 36-yr-old woman with six gallstones measuring 2.1 cm each. Within 21 h of methyl-tert-butyl ether (MTBE) treatment, the stones had dissolved to a small amount of residue. As could be seen from cholesterol concentrations of samples of aspirated gallbladder bile and MTBE fractions, the dissolution process was slow to begin with, and gained momentum during hours 6-11, after which it decelerated. We discontinued treatment after 20 h, since the stone residue showed no change. Cholecystoscopy performed with an Edwards angioscope via a catheter showed that there were no stone remnants, but that there were flat polyps on the gallbladder wall. One hour later, we stopped the therapy. Cholecystoscopy is a useful method of assessing the results of MTBE treatment.