High resolution electron scattering from high spin states in 208Pb.
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Biomedical subjects
Publications and source records attributed to M Leuschner.
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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.
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.
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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.
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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.
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 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.
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.
The influence of different solvents on cholesterol and pigment stones was investigated in vitro. Stone analysis was performed chemically, with infrared spectroscopy (IRS), scanning electron microscopy, energy-dispersive X-microanalysis (EDXA) and wave-length-dispersive X-microanalysis (WDXA). Each set of stones came from one source: eight human calcified cholesterol stones (CHS), eight fragments of bovine radiopaque Ca-bilirubinate stones (BBIL), and two complete BBIL. CHS and BBIL fragments were treated with (1) a buffered, alkaline 1% ethylenediamine tetraacetate solution (BA-EDTA; pH 9.5); (2) with BA-EDTA and monooctanoin preparation (GMOC) alternately; (3) with GMOC alone, and (4) with methyl-tert-butyl ether (MTBE). The complete BBIL were treated with BA-EDTA and MTBE. Furthermore, two human black pigment stones (BPS) were incubated in BA-EDTA. Calcified cholesterol stones are not dissolved by GMOC alone, nor by alternating treatment with BA-EDTA. They are dissolved by MTBE. MTBE is unsuitable for complete Ca-bilirubinate stones but MTBE, GMOC and GMOC/BA-EDTA alternately disaggregate stone fragments. This means that stone fragments behave differently from complete Ca-bilirubinate stones, which is important for further in vitro investigations. Ca-bilirubinate and black pigment stones are disaggregated in BA-EDTA. These results were confirmed with six CHS, 12 BBIL and 12 BPS from 5 further patients, incubated in the most eligible solvent for any individual stone type.
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.
The calcium chelating of different EDTA solutions was investigated after addition of 5.49% calcium bilirubinate powder. Calcium chelating seems to be an essential step in disaggregation of pigment stones. We found that Ca chelating is pH dependent and that the system must be buffered in order to prevent pH shifting during the dissolution process. When an alkaline (pH 9.4), buffered 1% EDTA solution is mixed with bile in a ratio of 70:30, dissolution of Ca will decrease to 60% as compared to investigations without bile. Furthermore, we could demonstrate that the EDTA solution would not only dissolve Ca bilirubinate powder, but complete bovine pigment stones of homogeneous structure and mostly inhomogenously composed stones of man as well.
Chemical dissolution of cholesterol gallstones using ursodeoxycholic acid (UDCA) in six patients with histologically confirmed HBsAg-negative chronic active hepatitis was started after a minimum of one year of therapy with steroids, azathioprine, or chloroquine and a treatment-free period of 8-15 months. The treatment with UDCA lasted 3-20 months with a daily dose of 8-11 mg/kg. Four patients served as controls. A decrease in transaminases (P less than 0.05) occurred in all patients during the UDCA therapy. After completion of the treatment, the figures rose again, but did not return to the initial value. The stones dissolved in five patients. A second liver biopsy was carried out in two patients after UDCA therapy, and this showed no detectable deterioration. Four patients refused biopsy because the laboratory parameters had improved under UDCA. A stone recurred in one patient six months after the end of therapy; the others have remained free of stones for up to 24 months.
786 consecutive patients with suspected gallstones investigated radiologically and ultrasonographically, 231 (33.0%) were found to have stones. Radiological examinations showed that 59.3% of these were suitable for chemical dissolution with cheno- or ursodeoxycholic acid. The percentage of treatable patients fell from age 20 to age 65 from 71% to 48% (p less than 0.05) and then rose again to 61% (not significant). The benefit of litholysis is greater, the earlier it is begun. The results are in disagreement with those of two studies in operated patients. Here only 19-24% were suitable for stone dissolution. Comparative ultrasonographic and radiological studies in 23 patients have shown that monitoring of patients during litholysis can be carried out ultrasonographically. Stone size measured ultrasonographically corresponds sufficiently accurately with that obtained radiographically.
Three therapeutic strategies are possible in a patient with asymptomatic or mildly symptomatic cholesterol gallstones: Cholecystectomy, medical gallstone dissolution, and expectant attitude. The course of cholelithiasis under these three strategies was evaluated by three decision trees. The incidences of possible complications were taken from the literature. For every complication the costs of drugs, absenteeism, treatment as outpatient and inpatient were listed. The costs multiplied by the likelihood of the complication represent the expected costs of the complication under consideration. The sum of the costs due to the initial treatment and the expected costs of all possible complications corresponds with the expected average costs of a therapeutic strategy. It is 21 000,- DM with medical gallstone dissolution, 25 000,- DM with immediate cholecystectomy, and 27 000,- DM with expectant attitude, respectively. Gallstone dissolution becomes more expensive than cholecystectomy only when its efficacy drops below 40%. The data show that the costs are less important for the choice of the therapy in cholelithiasis. The advantage of the decision tree lies in the fact that it describes the history and the costs of a disease by figures. Thereby, disagreement on the effects of a therapy on the course of the disease can be analysed and discussed more distinctly.
In two prospective studies including 962 patients and one retrospective study including 165 patients the problem was investigated, to what extend ultrasonography might change the diagnostic value of clinical examination, peritoneoscopy, guided liver biopsy and blind liver biopsy. It turned out, that liver biopsy is the method of choice in diffuse-parenchymatous disease (e.g. chronic active hepatitis, chronic persistent hepatitis, fatty liver), whereas laparoscopy is to be preferred if focal lesions (e.g. liver carcinoma) are present. Diffuse liver disease was present in 80% of the cases investigated; in this group of patients the diagnostic value of blind biopsy is equivalent to the diagnostic value of guided biopsy. Thus, blind biopsy does yield satisfactory results in most patients if it is possible to differentiate between diffuse and focal disease by ultrasonography. Such differentiation could be achieved in 77-98% of our cases, thus ultrasonography could intake a decrease in numbers of peritoneoscopies and an increase of blind liver biopsy.