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Biomedical subjects

M Delius

Publications and source records attributed to M Delius.

At least 37 records · Page 2Linked to original sources

Influence of dissolved and free gases on iodine release and cell killing by shock waves in vitro.

Exposure of a potassium iodide solution to lithotripter shock waves resulted in formation of iodine with the amount of iodine depending on the gas dissolved in the solution. Iodine yield was higher with O2 and Ar, as compared to CO2 and N2O; degassed solution revealed the lowest iodine yield. Exposure of L1210 mouse leukemia cells to shock waves reduced the number of viable cells with no difference between O2-, Ar-, or N2O-equilibrated and degassed conditions. CO2 equilibration resulted in a more pronounced reduction. The difference between chemical and biological effects argues against the involvement of free radicals in cell killing by shock waves. In additional experiments, gas bubbles of various sizes were introduced into the test vials. Addition of a 10 microL gas bubble revealed an over 10-fold increase in iodine yield from degassed potassium iodide solution with all gases. Addition of a gas bubble also reduced the number of viable cells again with no difference between the gases. It is suggested that shock wave-gas bubble interaction is an important mediator of iodine release and cell killing by shock waves.

Animals↗

In vitro interaction of lithotripter shock waves and cytotoxic drugs.

The effect of a combination of lithotripter shock waves and cytotoxic drugs was examined in vitro. L1210 cells in suspension were exposed to shock waves during incubation with cislatin, doxorubicin, daunorubicin, THP-doxorubicin, or aclacinomycin. Proliferation was determined using the 3-4,5 dimethylthiazol-2,5 diphenyl tetrazolium bromide assay. Dose enhancement ratios were calculated for each drug in order to determine the effect of the additional exposure to shock waves. In addition, partition coefficients and IC50s of the drugs were determined. It was found, that the dose enhancement ratios increased for the drugs with decreasing cytotoxicity. The effect of all five drugs was enhanced by shock waves to a higher degree at 7 min incubation as compared to 50 min incubation. The effect of cisplatin was most significantly enhanced, with a dose enhancement ratio of 6.7 at 7 min incubation. The enhancement increased with the operating voltage used for generating the shock waves, and was only present when cells were exposed to shock waves during the incubation with the drug. An increase in cellular membrane permeability is proposed as the mechanism of interaction between shock waves and drugs.

Aclarubicin↗

Sonographic imaging of extracorporeal shock wave effects in the liver and gallbladder of dogs.

During extracorporeal shock wave lithotripsy, changes in tissue echogenicity are observed by ultrasound. Their significance is not known. An experiment was performed in which 3,000 extracorporeal shock waves were applied under sonographic observation to the gallbladder wall of 6 dogs. No stones had been implanted, but transient shadows appeared simulating jumping stone fragments in the bladder. Echoes within the bladder lumen occurred in 3 dogs and were associated with hemorrhage into the lumen; in an additional ex vivo experiment, shock waves generated echoes in bile only after injection of a small amount of blood. In the liver, a transient increase in echogenicity was noted after a few shocks; it coincided with the region of tissue damage. Intense focal echoes occurred in the liver of 2 dogs at sites where a hematoma was found at autopsy. It is concluded that an increased focal echogenicity is an indicator of tissue damage by shock waves. The sonographic changes are thought to be caused by the transient generation of gas bubbles. The interaction of shock waves with gas bubbles is an established powerful mechanism which could explain the generation of tissue damage by shock waves.

Animals↗

Biological effects of shock waves: cell disruption, viability, and proliferation of L1210 cells exposed to shock waves in vitro.

L1210 cells were exposed in suspension to shock waves generated with a Dornier XL1 lithotripter. After 1000 discharges at 25 kV, the number of nondisrupted cells was 15% and the number of trypan blue excluding cells was 7% as compared to 100% in sham treated controls; the shock-wave effect was more prominent at higher voltages and less prominent at higher discharge numbers when compared at similar electrical input energies. Overall proliferation of cells which were trypan blue negative after exposure exceeded 70% of the proliferation of sham treated controls, except after 1000 shocks at 25 kV, where proliferation was reduced to 42%. The latter reduction in proliferation was found to be due to a reduced growth for 24 h after exposure, with a return to normal proliferation during the following days. Limiting dilution analysis revealed that the reduced growth was mainly due to a transitory increase of the doubling time and not to a reduction of the number of proliferating cells. Cell disruption by shock waves was completely inhibited by exposing the cells at an elevated pressure of 101 atmospheres, pointing to the possible involvement of cavitation in the shock wave effect.

Animals↗

Influence of the shock wave application mode on the growth of A-Mel 3 and SSK2 tumors in vivo.

We examined the influence of different shock wave application modes with a Dornier XL1 electrohydraulic lithotripter on the growth of A-Mel 3 and SSK2 tumors implanted under the dorsal skin of hamsters or mice. In a basic protocol, 500 shock waves a day on 4 consecutive days were administered at a discharge rate of 100 waves per minute and focused to the tumor center. This did not affect A-Mel 3 growth. A similar result was obtained with the basic protocol modified to 1000 shock waves a day and a wave application rate of 100 shock waves per second. Growth of A-Mel 3 and SSK2 tumors was significantly delayed, when the basic protocol was used, but the 500 shock waves a day were distributed over four points at the tumor edges and the tumor center. With the same shock wave protocol, lowering the water level over the tumor from 10 cm to 1 cm induced temporary regressions of SSK2 tumors. This was not due to the higher energy applied to the tumor, since twice the number of shock waves (1000 a day instead of 500 a day) was applied at a high water level and did not induce regressions. Four consecutive treatments with intervals between treatments shortened to 3 h and an additional treatment 12 h later at a low water level completely controlled tumor growth in 8 out of 12 SSK2 tumors for more than 150 days. The result showed that addition of a reflected wave from the water surface was most important for the shock wave effect, and suggested that shock wave devices generating similar wave forms should be applied for tumor therapy.

Animals↗

Biological effects of shock waves: effect of shock waves on the liver and gallbladder wall of dogs--administration rate dependence.

The effect of extracoporeal shock waves on the liver and the gallbladder wall was compared in two groups of dogs exposed to 1500 shock waves generated in an electrohydraulic lithotripter with 15 kV and 80 nF. The waves were focused on the gallbladder wall. In the experimental group, a shock wave burst of 10 consecutive waves with an interval of 10 ms between the waves was administered each second; in the control group, single shocks were released each second. The day following shock wave exposure, the dogs were anaesthetized, killed and then dissected. In the liver, subcapsular and intraparenchymal focal haemorrhages occurred in the high pressure field and venous thrombi in portal veins. There was a nonsignificant trend towards an increased number of venous thrombi after burst application. The gallbladder wall was haemorrhagic and oedematous, the mucosa was ulcerated in the focal area; blood clots were found in nearly all gallbladders. No differences were detected between the groups. The free plasma haemoglobin was only increased after fast shock wave administration. Increased haemolysis and the trend towards an increased number of thrombi favour cavitation as a mechanism of shock wave damage. The similar extent of tissue damage suggests that shock wave bursts can be applied for gallstone destruction in humans if the major liver vessels are kept out of the high pressure field.

Animals↗

Biological effects of shock waves: cavitation by shock waves in piglet liver.

Shock waves are known to generate cavitation in vitro. In vivo, extracorporeal shock waves may cause haemorrhages in tissues. Two types of changes were detected by conventional, real-time B-scan ultrasound when shock waves were administered to 5 piglet livers in vivo: transient changes consisting of bright signals in intrahepatic branches of the portal vein and tributaries of the hepatic vein, presumed to originate from gas bubbles, and stationary changes consisting of brightening of the area along the long axis of the high pressure field, presumed to indicate an increased number of gas-filled bubbles in this area. Transient changes appeared from the start of shock wave administration; bright signals were seen in liver vessels for several hundred microseconds before they were flushed away with the blood flow. Stationary changes appeared later, increased in intensity over several hundred shock waves and persisted for minutes after cessation of shock wave administration. Both types of signals were interpreted as direct evidence that lithotripter shock waves generated cavitation in vivo. Similar signals were received in the partly degassed water of the lithotripter tub. At autopsy of the piglets, focal intralobular haemorrhages and thrombi of portal veins were detected in the shock wave path. The occurrence of cavitation and tissue damage in the same gross area suggests that cavitation might be involved in the generation of tissue damage by shock waves.

Animals↗

Simulation of gallstone fragments by cavitation bubbles during extracorporeal shock wave lithotripsy: physical basis and in vitro demonstration.

During extracorporeal shock wave lithotripsy of gallstones, sonography often shows a swirling pattern of echogenic foci shortly after the application of shock waves. This effect has been thought to represent gallstone fragments in suspension. However, evidence suggests that this finding is in part due to cavitation, a physical phenomenon associated with the formation or movement of gas bubbles in the fluid-filled gallbladder. Condoms filled with degassed water and five human bile specimens were positioned in the focus of an MPL 9000 lithotriptor (Dornier Medical Systems, Munich). A solitary nonradiopaque gallstone was then added to a bile-filled condom, and the sonographic pattern was observed before and after fragmentation. The mean clearance time of the cavitation bubbles was 4 seconds for degassed water and 22 seconds for human bile. Gallstone fragments were distinguished from cavitation bubbles by their prolonged settling time (up to 30 minutes) along the dependent gallbladder wall.

Bile↗

In vitro cytotoxic activity of lithotripter shock waves combined with adriamycin or with cisplatin on L1210 mouse leukemia cells.

The effect of a combined treatment with shock waves generated by a lithotripter and Adriamycin or cisplatin was examined in cells that acutely survived exposure to shock waves and proliferated afterwards. Batches of 2 x 10(6) cells were exposed to the respective drug for 50 min or for 50 min plus 72 h. During the 50-min drug exposure 500 shock waves were applied at 25 kV. The growth as a percentage of the control was determined after 72 h by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cells treated with shock waves alone showed a growth inhibition as compared to control cells. For a 50-min drug exposure with Adriamycin the dose enhancement ratio did not exceed 1.3. For a 50-min drug exposure with cisplatin at concentrations of 0.5 micrograms/ml and 5.0 micrograms/ml, growth (as a percentage of the control) after combined treatment was significantly reduced as compared to cisplatin treatment alone; the dose enhancement ratio was 3.2 at 50% growth compared to the control. This indicates that shock waves can increase the susceptibility of L1210 cells to cisplatin. For a 50-min plus 72-h drug exposure no effect of an additional treatment with shock waves, as compared to chemotherapy alone, could be observed.

Animals↗

Investigation of cavitation in flowing media by lithotripter shock waves both in vitro and in vivo.

Cavitation produced by lithotripter shock waves was characterized in vitro in water and blood, and in vivo in aortic blood by means of a 1.6 MHz resonant bubble detector. This system was readily able to detect bubbles resulting from shock-wave induced cavitation in both water and blood flowing through plastic tubes in vitro, and even in blood pumped by the heart through a plastic arterio-venous shunt. However, this system was unable to detect evidence of shock-wave induced cavitational activity occurring within the intact vascular systems of dogs in vivo.

Animals↗

Shock-wave lithotripsy of gallbladder stones. The first 175 patients.

To substantiate the early results of extracorporeal shock-wave fragmentation of gallstones, we used this nonsurgical procedure to treat 175 patients with radiolucent gallbladder calculi. Chenodeoxycholic acid and ursodeoxycholic acid were administered as adjuvant litholytic therapy. The gallstones disintegrated in all patients except one and completely disappeared in 30 percent of all patients within 2 months after lithotripsy, in 48 percent at 2 to 4 months, in 63 percent at 4 to 8 months, in 78 percent at 8 to 12 months, and in 91 percent at 12 to 18 months. In patients with solitary stones up to 20 mm in diameter, the corresponding values were 45, 69, 78, 86, and 95 percent, respectively. Shock-wave therapy had no adverse effects except cutaneous petechiae (14 percent) and transient gross hematuria (3 percent). One third of the patients had one or more episodes of biliary colic before all the fragments disappeared. Two patients had mild pancreatitis, which necessitated endoscopic sphincterotomy in one. The patient with insufficient stone fragmentation underwent elective cholecystectomy; no additional operations were necessary. Extracorporeal shock-wave lithotripsy combined with medical therapy for stone dissolution is a safe and effective treatment in selected patients with radiolucent gallbladder calculi.

Adolescent↗

Biliary stones: treatment by shock-wave lithotripsy.

Extracorporeal shock-wave lithotripsy has been introduced as a novel nonsurgical therapy for gallstone disease. To substantiate the initial results, more than 400 patients with biliary calculi have been treated. In selected patients with gallbladder stones, complete clearance of all stone fragments can be expected within 1 year in about 80%. In patients with bile-duct stones not amenable to endoscopic measures, sufficient stone fragmentation by extracorporeal shock waves was achieved in about 80%. Extracorporeal shock-wave lithotripsy is a safe and efficient therapy for selected patients with gallbladder calculi. For patients with bile-duct stones not amenable to endoscopic measures it offers a nonsurgical alternative.

Chenodeoxycholic Acid↗

Biological effects of shock waves: kidney haemorrhage by shock waves in dogs--administration rate dependence.

The effect of shock waves on normal canine kidneys was examined in two groups of dogs whose right kidneys were exposed to 3000 shock waves generated with 20 kV and 40 nF in a Dornier HM II lithotripter. The groups differed only in the rate of shock wave administration which was 100 and 1 per second, respectively. Autopsy was performed 24 to 30 h later. Macroscopically and histologically, significantly more haemorrhages occurred in the kidney parenchyma if shock waves were administered at a rate of 100 waves per second. Haemorrhages were diffuse, the outer medulla was most heavily affected. The results show that kidney damage is dependent on the rate of shock wave administration. They argue against a direct shock wave effect and favor cavitation as the mechanism of shock wave damage although thermal effects cannot be excluded.

Animals↗

Biological effects of shock waves: kidney damage by shock waves in dogs--dose dependence.

The effect of shock waves on normal canine kidneys was examined in three groups of dogs whose right kidneys were exposed to 500, 1500, or 3000 shock waves. Autopsy was performed 24-30 h later. The kidneys were enlarged with haemorrhages in the outer and inner renal capsule and intraparenchymally. Macroscopically intraparenchymal haemorrhages were restricted to the high pressure field of the shock wave and consisted of haematomas up to 18 mm diameter (most frequently 6 mm or less) and diffuse haemorrhages. Histologically, haemorrhages were shown to originate from interlobular and arcuate veins. Venous thrombosis, tubular dilatation, and diffuse interstitial haemorrhage occurred in the same area. The number of haematomas was larger, and diffuse haemorrhages were more extended after the application of 1500 and 3000 than after 500 shock waves. No difference was seen between 1500 and 3000 shock waves.

Animals↗