Biomedical subjects
Publications and source records attributed to J Schüller.
Deep structures of the bladder wall can be examined by intravesical ultrasonic tomography. Therefore this technique is an ideal supplement to cystoscopy. Typical ultrasonic findings of 58 patients with different lesions of the bladder wall are presented.
Regional hepatic blood flow was measured by two methods using 133-Xenon washout technique: 1. "portal method" (injection of 133-Xenon into the spleen), and 2. "arterial method" (direct application of 133-Xenon into the A. hepatica propria by an indwelling catheter after celiacography). The portal method was performed in 38 patients (30 patients with cirrhosis of the liver, 4 patients with chronic hepatitis, 4 controls with normal liver function). The results show that using this method regional liver blood flow can be measured accurately. Patients with cirrhosis of the liver had a highly significantly decreased hepatic blood flow in comparison to the control group. The advantage of this method is that extra- and intrahepatic shunts can be visualized simultaneously. However, using this method in patients with hemodynamically very effective extrahepatic collaterals the tracer does not reach the liver. In these patients regional hepatic blood flow can be estimated by the arterial method (12 patients with cirrhosis of the liver, 2 with normal liver function). However, no information about the morphology of the portal circulation can be obtained using this method. Direct comparison of the quantitative estimation of regional hepatic blood flow was performed in 6 patients. The data obtained by the 2 methods correlated highly significantly (r = 0.91).
Compensatory increase of hepatic artery blood flow follows protosystemic shunt surgery. Parathormone stimulates significantly blood circulation through the hepatic artery. This stimulating effect is used to test vasodilative capability of the hepatic artery prior to shunt surgery. We report our findings on a additional increase of the hepatic artery blood flow under Parathormone. A portal-caval end-to-lateral shunt surgery caused an increase in blood flow 71 percent on an average compared to the basic value. After administration of Parathormone we observed an additional increase of 13,5 percent. This result indicates, that the hepatic artery will be dilated by Parathormone after a portocaval shunt too.
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A prerequisite for the therapeutic procedure in bladder carcinoma is the determination of the depth of infiltration and extent of the tumor. This is possible by means of intravesical ultrasonic tomography as studies in 19 patients with vesical tumors of different sizes and extent showed. Histologically verified infiltration depths correlated with the intravesical ultrasonic findings in all cases so far. A statement on the percentage accuracy of the sonographic findings is not yet possible because of the small number of cases so far.
The results of 67-gallium scanning in 644 patients with histological confirmation of diagnosis are presented. 67-Ga uptake was recorded in 93.3% of 312 malignant and in 85.8% of 332 benign conditions. In 89.4% 67-Ga was successful in distinguishing between malignant and benign disorders. In 58 of 62 lesions due to malignant lymphoma 67-Ga uptake was seen. 67-Ga scanning is an indispensable tool for early diagnosis of hepatoma (n = 80) and an important non-invasive staging procedure for lymphoma patients which complements exploratory laparotomy.
Methotrexate-citrovorum factor (MTX-CF) therapy was administered to 20 patients with advanced renal cell carcinoma. Eight patients were treated with MTX-CF only. Two patients who received short-term rescue showed partial remissions along with severe toxicity including gastrointestinal symptoms and bone marrow depression. Twelve patients were treated with a combination of MTX-CF, vincristine, bleomycin, and an alkylating agent (either peptichemio or cyclophosphamide). In this latter group, patients with a glomerular filtration rate of greater than 70 ml/minute received 150-400 mg/m2/cycle of MTX. Patients with decreased renal function (less than 70 ml/minute) received 35-100 mg/m2/cycle of MTX. Two of seven patients with a decreased glomerular filtration rate showed partial remissions and four patients had static disease. One patient in the group of five with normal renal function showed static disease. None showed objective improvement. The median survival time was 25 months for patients with partial remission and static disease and 4.75 months for patients with progression. This difference is highly significant (P less than 0.0005). These results seem to justify further investigations of MTX-CF therapy in hypernephromas, even in the presence of impaired renal function.
In portosystemic shunt surgery, there still is a lack of correlation between various preoperative hemodynamic measurements and the postoperative clinical course of patients. The magnitude of post-shunt increment in hepatic arterial flow was found to be directly related to long term prognosis. To predict the arterial response for selecting patients for shunting, we tried to use a new non invasive method: Arterial and portal components of total liver blood flow were determined quantitatively by "Sequential hepato-splenic scintigraphy". Dilatation capability of the hepatic artery, was tested by means of the hemodynamic action of Parathyroid hormone (PH). PH has been found to induce a large and exclusive augmentation of hepatic arterial blood flow. We were able to document a statistically highly significant increase in hepatic arterial flow following i. v. applications of PH. The extent of arterial increment appears to be dependent upon the degree of entrapment of the hepatic arterioles by the fibrous tissues of cirrhosis.
The influence of dopamine on glomerular filtration rate (GFR), renal plasma flow (ERPF) and urinary sodium excretion was investigated in dogs before and after a chronic bile duct ligation for a period of 16 days. 1. Dopamine (4 microgram/kg/min.) leads to an increase of GFR, ERPF and urinary sodium excretion. 2. There was no change of GFR and ERPF after bile duct ligation. Urinary sodium excretion was decreased. The decrease was, however, not significant (0.05 less than p less than 0.1). 3. After bile duct ligation dopamine induced increase of GFR and ERPF was of the same order as observed in the preoperative period. Compared with the preoperative values for sodium excretion the dopamine effect was lower (p less than 0.05). The present investigation shows that dopamine is worth trying in cases of obstructive jaundice accompanied by acute renal failure.
Reflux-induced strictures of anastomoses are well-known complications of total gastrectomys. Since 1974 ten patients with postoperative dysphagia were treated by endoscopy. The enlargement of the obstructed anastomotic ring was done with the unopened diathermy-snare. This simple and uncomplicated method removed the heavy complaints of the patients immediately; no complications were registered until now. Follow-up was 3 to 32 months.
This paper reports on the clinical applicability and efficiency of Scintiphotosplenoportography (SPSP) by means of 99mTc Pertechnetate. This diagnostic process permits obtaining the following data: actual route and patency of the portal vein, localizing of collaterals, as well as information on the actual speed of portal flow. By determining the time of transit of the radionuclid via the collateral pathways into systemic circulation, additional assessments as to the hemodynamic functional importance of these collaterals can be made. This process is of particular value for the speedy assessment of the patency of a surgically effected portocaval shunt in cases of shunt-bleeders. In patients without cirrhosis, a stop in the filling along the course of the portal vein indicates portal thrombosis. In cases of manifest cirrhosis, however, the lack of an SPSP image for the proximal portal vein and the liver itself, merely points to the existence of extensive caudal collaterals. Traumatization as the result of intrasplenal application of a volume of less than 1 ml (of tracer) remains minimal. In contrast with radiological splenoportography this methods entails practically no risks. However, as a result of the restricted field of view and the relatively coarse power of resolution, the quality obtainable by szintiphotosplenoportography is somewhat inferior to that of X-ray splenoportography.
The effect of dopamine on liver function and on renal blood flow and the glomerular filtration rate was studied in 13 patients suffering from liver cirrhosis. Hence, the BSP retention and 131I BSP clearance was determined and also the clearance of 99mTc DTPA and of 125I hippuran in decreasing concentrations, as well as under steady state conditions. Methodological problems arising from the application of the slope clearance technique in cirrhotic patients are discussed. Dopamine did not affect the BSP clearance and BSP retention, but a significant increase in renal plasma flow was observed. The glomerular filtration rate was not significant altered.
1. An infusion of 3 gamma/kg/min dopamine causes a significant increase in the renal plasma flow and the glomerulum filtration rate. This dosage does not cause a change of the mean systolic and arterial pressure. This effect may also be observed in patients with hepatic cirrhosis. 2. The wedged hepatic vein pressure, an indicator for the portal pressure, only shows a slight increase (9,46 +/- 9,41%) as compared to the initial pressure produced by the mentioned dose. Measurements of the spleen pulpa pressure, which likewise indicates the portal pressure, showed an increase of pressure up to 100% due to pressing or coughing. 3. If in the case of bleeding oesophageal varices acute renal failure might develop, the advantage of the effect of dopamine in stimulating the blood flow through the kidneys may be considered more important than the minute danger of a slight increase of the portal pressure, which might provoke haemorrhage.
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The pharmacokinetics of mitomycin C after chemobolisation of the common hepatic artery by micronized Spherex starch particles (mean particle size 30 microns) were investigated in 5 cancer patients. Bolus injection and simultaneous occlusion of the artery lead to a significantly lower systemic circulation of mitomycin C in the blood vessel system than after bolus injection without chemobolisation. The plasma concentration-time curves showed lower values in the alpha-phase in the presence of Spherex (co = 743 ng/ml) than without starch particles (co = 987 ng/ml). Accordingly, the AUC values were significantly lower too (AUC = 28.6 micrograms/ml.h with Spherex and 39.7 micrograms/ml.h without Spherex), thus leading to a lower systemic bioavailability of the drug and a higher local bioavailability in the tumor region. Elimination of mitomycin from the central compartment was similar for both administrations (t1/2 = 27 min with Spherex and 28 min without Spherex) and showed the characteristic profile of the substance. The clinical picture showed a milder toxicity with a certain loss of side effects. These results indicate a significant and desirable change in the pharmacokinetics of mitomycin C during the distribution phase into the tissue of patients.
The blood plasma levels of 5-fluorouracil (5FU) after i.v. administration have been determined without and under the influence of 1, 5 or 9 million units (MU) preadministered interferon (IFN) in patients with gastrointestinal carcinoma. The co-administration of 9 MU IFN causes a doubled increase of the 5FU serum concentrations combined with a statistically significant change of the pharmacokinetics of 5FU for c0, AUC, Vd and Cltot (P < 0.005). A similar effect with distinctly increased serum concentrations could be observed for the preadministration of 5 mU IFN whereby c0 and AUC were elevated significantly (P < 0.05), but not Vd, Cltot and cd. The preadministration of 1 MU IFN also leads to higher plasma levels, but no changes in the pharmacokinetics of 5FU could be calculated (P > 0.05). A linear correlation between the IFN dose and the pharmacokinetic parameters c0 (R = 0.958), AUC0-120 (R = 0.948), Vd (R = 0.941) and Cltot (R = 0.963) of 5FU could be found (P < 0.05), but not for the coefficient of distribution and t1/2el. The results indicate that the pharmacokinetics of 5FU might be influenced by the preadministered IFN dose.
The pharmacokinetic parameters of mitoxantrone in patients with liver metastasis after intra-arterial 2 h and 24 h infusion (dosage 12 mg/m2) were investigated. Peak plasma concentrations were 305 +/- 60 ng/ml at 2 h infusion and 244 +/- 89 ng/ml at 24 h infusion. These peak plasma concentrations occurred at 0.9 +/- 0.8 h during 2 h infusion and 5.5 +/- 3.4 h during 24 h infusion. No significant difference between both intra-arterial administrations in elimination half-life (50-223 h at 2 h infusion, 58-246 h at 24 h infusion) and area under the plasma concentration-time curve (AUC0-72 = 11.6 micrograms/ml.h for 2 h infusion, AUC0-72 = 11.2 micrograms/ml.h for 24 h infusion) could be found. The results indicate that no change of availability in the central compartment at infusion of mitoxantrone over a period of 24 h could be achieved. The 2 h infusion lead to sufficient plasma levels with pharmacokinetic parameters of mitoxantrone similar to 24 h infusion and showed a good clinical picture with mild toxicity.
The influence of interferon (IFN) coadministered subcutaneously with the biomodulating agent folinic acid on the blood serum levels of 5-formyl-tetrahydrofolic acid (CHO-THFA) and the biotransformation into its main metabolite in the blood 5-methyltetrahydrofolic acid (CH3-THFA) was studied in patients receiving a chemotherapy with 5-fluorouracil. IFN causes a clear decrease of the serum concentrations of CHO-THFA and a statistically significant decrease of CH3-THFA concentrations (P < 0.01). The effect on serum concentrations could be observed in each patient, but in a different order of magnitude. As a consequence, the preadministration of IFN leads to a significant change in the basic pharmacokinetic parameters of both compounds: the mean area under the concentration-time curve is decreased at 27.4% for CHO-THFA (P < 0.025) and at 22.4% for CH3-THFA (P < 0.025), respectively. The total body clearance is elevated at 45.4% for CHO-THFA (P < 0.05) and at 23.4% for CH3-THFA (P < 0.05). The mean volume of distribution is increased by IFN at 38.2% for CHO-THFA (P < 0.025) and at 22.3% for CH3-THFA (P < 0.05). The nearly identical mean residence time in both groups indicates that CHO-THFA elimination is not affected by IFN. But the results prove a certain interaction between IFN and CHO-THFA. IFN accelerates the distribution of CHO-THFA as well as of its main metabolite from the blood into the tissue or activates the biotransformation of CHO-THFA into CH3-THFA inside the cells of the tissue. The extent of biotransformation of CHO-THFA into CH3-THFA, which takes place in the blood, is not influenced by IFN because percentage AUC-ratios CHO-THFA:CH3-THFA were 89.5:10.5% for the control group and 88.8:11.2% for the IFN group.