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M Neubrand

Publications and source records attributed to M Neubrand.

At least 37 records · Page 2Linked to original sources

Gallbladder emptying determines early gallstone clearance after shock-wave lithotripsy.

BACKGROUND/AIMS: Disappearance of gallbladder stones after shock-wave lithotripsy combined with bile acid therapy depends on mechanical evacuation and dissolution of fragments. Many patients with gallstones have impaired gallbladder emptying and may show delayed stone clearance after lithotripsy. METHODS: The effect of gallbladder emptying on gallstone clearance after lithotripsy was prospectively studied in 57 patients with one radiolucent gallbladder stone < or = 20 mm. Gallbladder emptying was assessed sonographically before and after 2 weeks of ursodeoxycholic acid (UDCA) treatment. RESULTS: UDCA increased gallbladder fasting and residual volume and decreased ejection rate but did not affect ejection fraction. Patients with an ejection fraction > 60% achieved complete gallstone clearance after lithotripsy in a higher percentage than patients with smaller ejection fractions (1 month, 31% vs. 7%, P = 0.022; 2 months, 55% vs. 18%, P = 0.003; 3 months, 66% vs. 29%, P = 0.005). Patients who became stone-free within 1 month showed larger ejection fractions than patients with retained fragments (67% +/- 4% vs. 56% +/- 3% before UDCA, P = 0.032; 65% +/- 4% vs. 53% +/- 3% with UDCA, P = 0.017). Further, ejection rate during UDCA therapy was larger in patients with complete gallstone disappearance within 1 month than in patients with delayed fragment clearance (1.57%/min +/- 0.36%/min vs. 0.76%/min +/- 0.09%/min; P = 0.002). CONCLUSIONS: Gallbladder emptying is a major determinant of early gallstone clearance after lithotripsy.

Adult↗

Gallstone recurrence after shock-wave therapy.

BACKGROUND/AIMS: The long-term outcome of nonoperative gallstone therapy depends on both absence of stones and absence of biliary pain. The aim of the present study was to determine the rate of stone recurrence and the rate of symptoms within 5 years after successful shock wave lithotripsy combined with bile acid therapy. METHODS: One hundred consecutive patients (single stones, n = 89; 2 or 3 stones, n = 11) were followed up for a median of 4.3 years after stone disappearance and discontinuation of bile acids. RESULTS: Twenty-three of the 100 patients developed recurrent stones. Calculated by actuarial analysis, the recurrence rate was 7% +/- 3%, 11% +/- 3%, 13% +/- 4%, 20% +/- 5%, and 31% +/- 7% (mean +/- SD) at 1, 2, 3, 4, and 5 years, respectively. The recurrent stones were small (6 +/- 5 mm) and were associated with recurrent biliary pain in 14 (61%) of the 23 patients. Repeated shock wave lithotripsy and/or bile acid medication resulted in stone disappearance in only 10 of 20 patients with recurrence. CONCLUSIONS: The long-term rate of stone recurrence after lithotripsy of primarily solitary gallbladder calculi is lower than expected from post-bile acid dissolution trials. Recurrence of stones frequently is associated with recurrence of biliary pain.

Adult↗

Combination of extracorporeal shock-wave lithotripsy and dissolution of gallbladder stones with methyl tert-butyl ether: a randomized study.

We conducted a prospective randomized study in gallstone patients to determine whether a combination of extracorporeal shock-wave lithotripsy and subsequent dissolution with methyl tert-butyl ether increases the success rate of methyl tert-butyl ether dissolution and shortens treatment time compared with monotherapy with methyl tert-butyl ether. Fifty patients were randomized into two groups. Twenty-five patients underwent extracorporeal shock-wave lithotripsy before contact dissolution with methyl tert-butyl ether, and 25 patients were treated with methyl tert-butyl ether alone. All patients had at least three stones or stones larger than 30 mm that were radiolucent on x-ray and had densities of less than 140 Hounsfield Units (HU) on computed tomography. Overall, the combined approach neither shortened the treatment time significantly vs. monotherapy with methyl tert-butyl ether nor reduced the time of hospitalization. The success rate was slightly but not significantly increased compared with that of methyl tert-butyl ether therapy alone. The recurrence rate was similar in the two groups after a median follow-up of 1 yr. However, when subgroups of patients with at least one stone larger than 15 mm or with stones with densities of more than 60 HU were analyzed, the clearance rate after 5 mo was significantly higher (p < 0.005 and p < 0.025, respectively) in patients subjected to a combination of extracorporeal shock-wave lithotripsy and methyl tert-butyl ether dissolution. Extracorporeal shock-wave lithotripsy and methyl tert-butyl ether did not expose patients to more adverse effects than did treatment with methyl tert-butyl ether alone.

Adult↗

In vitro study to elucidate the physical laws concerning the fragmentation of both solitary and multiple artificial stones.

These in vitro studies define the basic physical laws regarding work and energy for the successful fragmentation of human gallstones. For this purpose a standardized stone model was used consisting of plaster and glass microspheres with physical properties similar to those of human gallstones. All experiments were performed using the lithotripter model MPL9000 (Dornier). The acoustic energy passing stones of 10-30 mm ranged between 8 and 90 mJ per pulse depending on the stone size and energy setting. These results represent the basis for the three following investigations. In the first experiment the relationship between fragmentation and shock wave energy was investigated in a basket with 2 mm mesh size. Thus no layer of small fragments could shadow the acoustic energy for further fragmentation of larger fragments. A constant amount of stone material was found to be fragmented per shock-wave pulse irrespective of stone volume. A low energy threshold (2 mJ/cm3) was observed, below which fragmentation did not occur. In the second experiment, the sieve was covered with a membrane, thus simulating the in vivo situation. The presence of a layer of small fragments hindered the further disintegration of the larger fragments. The attenuation depended to a large extent on original stone volume and acoustic energy per pulse. The corresponding attenuation factor increased with the original stone volume. Thus the fragmentation of a stone with a diameter of 30 mm was attenuated twice as much as a stone of 20 mm size. The critical layer thickness at which no further disintegration took place was 2.5 mm at 18 kV, 4.2 mm at 22 kV, and 5.0 mm at 26 kV.(ABSTRACT TRUNCATED AT 250 WORDS)

Biophysical Phenomena↗

Biotransformation of orally administered ursodeoxycholic acid in man as observed in gallbladder bile, serum and urine.

The aim of this study was to evaluate the biotransformation of orally administered ursodeoxycholic acid in man. The distribution of ursodeoxycholic acid and its metabolites in gallbladder bile, in serum and in urine with emphasis on separation of their unconjugated, amidated and sulfated species in particular, was investigated. Seven gallstone patients were given 750 mg of ursodeoxycholic acid daily for 2-3 weeks. Six gallstone patients who did not receive ursodeoxycholic acid served as controls. Ursodeoxycholic acid became the major bile acid in gallbladder bile contributing 43% to total bile acids. 2% of biliary ursodeoxycholic acids were in the unconjugated form, 87% in the amidated form and 11% in the sulfated form. Iso-ursodeoxycholic acid was found in bile in small amounts and was present only as the sulfated species and not as the amidated one. Other metabolites of ursodeoxycholic acid tentatively identified in bile were 1 beta, 12 beta, 6 alpha- and 21,22-hydroxylated derivatives of ursodeoxycholic acid. Lithocholic acid in bile tended to increase under ursodeoxycholic acid treatment and was positively correlated to ursodeoxycholic acid. The concentration of cholic acid in bile decreased significantly whereas the levels of deoxycholic acid and chenodeoxycholic acid did not change. Total bile acid concentration in serum and excretion of bile acids in urine increased from 5.4 +/- 1.1 to 18.4 +/- 9.5 mumol l-1 (mean +/- SD, P < 0.005) and from 5.6 +/- 1.3 to 13.1 +/- 7.9 mumol g-1 creatinine (mean +/- SD, P < 0.05) after ursodeoxycholic acid ingestion mainly due to spillover and excretion of ursodeoxycholic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

[Laparoscopic cholecystectomy of large gallbladder calculi].

Laparoscopic cholecystectomy is more laborious in patients with large gallbladder stones in that they can only be removed safely after an enlargement of one incision or intraoperative lithotripsy. Preoperative extracorporeal shock-wave lithotripsy (ESWL) might theoretically solve this problem and facilitate the extraction of the gallbladder. Ten patients with minimum one stone > 20 mm of diameter received ESWL treatment within 24 h before operation. Complete pulverization of stones was achieved in only one patient. Additional mechanical fragmentation by forceps was necessary in 7 and an enlargement of the incision in 5 of 10 patients. Compared to 10 patients with corresponding stones and mechanical lithotripsy ESWL showed no advantage and cannot be recommended because of increase of costs.

Adult↗

Noninvasive therapy of gallbladder calculi with a radiopaque rim.

Safety and efficacy of shock-wave lithotripsy and bile acid dissolution therapy of patients with gallbladder calculi with a radiopaque rim were evaluated. Eighty-six patients with symptomatic solitary stones were treated by this noninvasive therapy and were followed up to 18 months. Three different lithotripsy treatment modalities were used. Up to 1600 shock wave discharges were applied. Patients in group A (n = 20) were treated with an electrohydraulic water-bath lithotripter at a discharge voltage of 18 +/- 1 kV (mean +/- SD), group B patients (n = 25) were treated with an electrohydraulic water-cushion lithotripter at 19 +/- 2 kV, and group C patients were treated (n = 41) with the same lithotripter at 22 +/- 2 kV. Five to eight months after lithotripsy, 15% in group A were free of fragments compared with only 4% in group B (NS vs. group A), and 38% in group C had no stones (NS vs. group A; P = 0.007 vs. B). Thirteen to eighteen months after lithotripsy, the respective results were 59% in group A, 37% in group B (NS vs. group A), and 68% in group C (NS vs. group A; P = 0.05 vs. group B). Patients with fragments of less than or equal to 3 mm in diameter showed significantly better fragment clearance than those with larger fragments. The frequency of adverse effects was not significantly different between the three groups. Biliary colic occurred in 43% of the patients and mild biliary pancreatitis in 3 patients. Endoscopic sphincterotomy was required in 1 patient, and elective cholecystectomy was performed in 6 patients. Using a water-cushion lithotripter at high-power setting, selected patients with solitary gallbladder stones with a radiopaque rim may be treated safely and successfully by shock-wave lithotripsy combined with bile acid dissolution therapy.

Administration, Oral↗

Nonsurgical management of gallstones.

Nonsurgical management of gallstones has made considerable progress within the past 20 years. More than 95% of all patients with bile duct stones can be treated successfully by peroral endoscopic or percutaneous techniques. In the case of very large or impacted calculi, intracorporeal or extracorporeal lithotripsy is available (Figure 9-10). Mortality from these approaches is low (in the range of 1%) despite the fact that most patients are elderly and frail, and open surgery is rarely required. While nonsurgical management of bile duct stones is commonly accepted, there is disagreement as to whether gallbladder stones should be managed nonsurgically, especially in view of the introduction of laparoscopic cholecystectomy. For patients in good general health who are willing to undergo surgery, removal of the gallbladder is the treatment of choice. However, there are some patients in whom a nonsurgical procedure ought to be considered. These are patients with a patent cystic duct, a functioning gallbladder, and symptomatic, radiolucent stones who can be scheduled for elective treatment. In patients with small floating stones, solitary radiolucent stones or even multiple large stones with a CT density lower than 50 HU, the chance of complete clearance of the gallbladder ranges between 80% and 90% using oral dissolution therapy, direct contact dissolution, or a combination of extracorporeal lithotripsy and dissolution. Each method has its ideal candidates (Table 9-1). The overall percentage of patients with gallstones for these nonsurgical therapeutic options is probably not higher than 20%. Therefore, the impact on surgery is still minor. Controlled clinical comparisons of the different therapies are lacking at the moment. However, these approaches have already stimulated further research into the pathogenesis of gallbladder stone disease and will no doubt undergo further improvement. Drugs that, in addition to ursodeoxycholic acid, further reduce cholesterol saturation in bile such as 3-hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors are already under investigation for oral treatment of gallstones in combination with bile acids. Further studies will also clarify the influence of gallbladder motility and certain bile constituents, such as proteins, on clearance of gallstones and recurrence after successful nonsurgical management. Thus, nonsurgical options, which obviate the necessity for general anesthesia and eliminate the risk of bile duct injury, will certainly continue to play a role in the management of gallbladder stones.

Bile Acids and Salts↗

Does computed tomography improve patients selection for extracorporeal shock wave lithotripsy (ESWL) of radiolucent gallbladder stones?

In 97 patients with radiolucent solitary gallbladder stones, the density of the calculi was evaluated by computed tomography (CT) prior to extracorporeal shock wave lithotripsy (ESWL). Sixty-three percent of the stones were isodense to bile (mean 48 +/- SD 11 HU), and 37% could be identified on CT-sections (maximal density 105 +/- 46 HU, mean density at the largest cross-section 53 +/- 31 HU). There was a slight trend toward better stone fragmentation and higher clearance rate in patients with isodense stones. However, the probability of complete fragment clearance was not significantly different in stones with a high or low CT-density. From these data we conclude that stone selection for ESWL and adjuvant bile acid therapy in patients with radiolucent solitary stones as assessed by oral cholecystography is only marginally improved by computed tomography.

Adult↗

[Effect of carteolol and timolol eyedrops on the pressure tolerance of the optic nerve head].

In a planned, randomized, double blind study ocular perfusion pressures were measured before and after a 3-day regimen of 2% carteolol hydrochloride or 0.5% timolol maleate. A pressure tolerance test was also carried out. The results of this test revealed the critical pressure: it is the artificially increased intraocular pressure at which the visual function (monitored by visually evoked cortical potentials) is reduced to 20% of its initial value. The ocular perfusion pressures are affected by both drugs. They are more clearly reduced by carteolol than by timolol. The critical pressure is affected by both drugs too. After application of carteolol, the critical pressure is clearly lower than after application of timolol. The difference is statistically significant (p less than 0.05).

Adaptation, Physiological↗

In vitro cholesterol gallstone dissolution after fragmentation with shock waves.

In order to test whether shock wave fragmentation of human gallstones increases their dissolution rates in a bile acid-lecithin solution, we carried out in vitro experiments. Stones comparable in size, weight and cholesterol content (86%) from the same human gallbladder were disintegrated by shock waves. A glycoursodeoxycholic acid (GUDC)-lecithin solution served as solvent. After 10 days incubation in this solvent, intact stones had lost only 4% of their cholesterol. This value increased to 92% after disintegration of the stones by 300 shock wave discharges. Fragments with a size of less than 2 mm had lost 55% of their cholesterol after day 1 and 99% after day 10. A large stone fragment cleaved off by shock waves lost much more cholesterol (42% after 10 days) than an intact untreated stone (4% after 10 days) comparable in size, weight and cholesterol content. These data show that shock wave lithotripsy of cholesterol gallstones considerably accelerates their dissolution rate in a GUDC-lecithin solvent, the desirable fragment size being 2 mm or less. However, even large fragments may lose much more cholesterol than comparable intact stones as a result of changes in surface structure as documented by scanning electron microscopy. The experiments favor the concept of a combined treatment of gallbladder stones by extracorporeally generated shock waves and bile salt therapy.

Cholelithiasis↗

Fragmentation of gallstones using extracorporeal shock waves: an in vitro study.

Eighty in vitro experiments were performed with single (n = 51) or multiple (n = 29) gallstones in order to find out which parameters are of prime importance for their disintegration by extracorporeal shock waves. A Dornier lithotripter and an upper limit of 1,500 discharges were employed. Although computed tomography density was significantly lower in cholesterol stones than in the noncholesterol stones (p less than 0.0001) and although the latter were significantly more often radiopaque (p less than 0.0001), we found no clear-cut correlation between the cholesterol content or computed tomography density and the degree of fragmentation of the stones. The most important variable which limited successful disintegration was the total stone volume. In stones with a mean total volume of 0.83 ml +/- 0.25 S.E. (diameter for single stones = 11.5 +/- 0.9 mm), none of the fragments exceeded 2 mm, whereas in stones with a mean volume of 3.6 ml +/- 0.64 (diameter = 17.2 +/- 1.5 mm) at least one fragment larger than 2 mm remained (p less than 0.002). Under the in vitro conditions, fragmentation was similar in multiple and solitary stones, provided the volume of the stones was comparable. These data show that, in general, the number and size of the stones, i.e. their total volume, and much less significantly their chemical composition are the major determinants of fragmentation by extracorporeal shock waves.

Absorptiometry, Photon↗