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Biomedical subjects

U Räth

Publications and source records attributed to U Räth.

33 records · Page 2Linked to original sources
PubMed1991

Effect of intraperitoneal recombinant human tumour necrosis factor alpha on malignant ascites.

29 patients with refractory malignant ascites due to metastatic peritoneal spread of adenocarcinomas originating from the ovary, gastrointestinal tract, liver, breast and uterus were treated in a phase I trial of intraperitoneal infusions of recombinant human tumour necrosis factor alpha (rhTNF-alpha). Patients received 40-350 micrograms/m2 rhTNF-alpha intraperitoneally once weekly for 2 months or for a shorter period in case of early resolution of ascites. Systemic side-effects resembled those reported for rhTNF-alpha given intravenously. No dose-limiting toxicities were found and thus a maximum tolerated dose of intraperitoneal rhTNF-alpha was not established. Out of 29 patients, 22 responded with a complete (16) or partial (6) resolution of their ascites. There was a less than 50% reduction in 4, and no increase in ascites in 1. 1 patient showed progressive ascites formation, and another patient was not eligible because of early death unrelated to treatment. Trials in patients with smaller tumour burden are warranted.

Adenocarcinoma↗
PubMed1990

Etoposide, adriamycin, and cisplatinum (EAP) combination chemotherapy for advanced gastric cancer. A phase II trial by the "Chemotherapiegruppe Gastrointestinaler Tumoren (CGT)".

In a multicenter trial, 49 patients with histologically proven advanced gastric cancer were treated with a combination chemotherapy consisting of etoposide 120 mg/m2 d 4, 5, 6 adriamycin 20 mg/m2 d 1, 7 and cisplatinum 40 mg/m2 d 2, 8. Therapy was repeated every 4 weeks, 45 patients were evaluable for response after 8 weeks of treatment. Eight patients achieved a partial remission (PR: 18%), 17 patients had no change (NC: 38%), and 20 patients showed tumor progression (P: 44%). Four patients with primarily inoperable tumor and without distant metastases who achieved a partial remission, underwent second look operation with curative intention. All 4 patients died within 12 months after second look operation due to tumor recurrence. Median survival time of all patients was 9 months. Toxicity was considerable. WHO grade 3/4 toxicity appeared in 20-30% of patients (nausea, vomiting, loss of appetite, leucopenia). After 3 cycles complete alopecia was present in 70% of patients. Severe infection, requiring treatment, occurred in 10 patients. Five patients discontinued therapy because of intolerable subjective toxicity. The observed response rate of 18% objective partial remissions is disappointing and does not give support to the communications reporting response rates over 50% with EAP and other regimens including cisplatinum. In conclusion, and considering the high subjective and objective toxicity of this regimen, it can not be recommended for standard use in patients with advanced gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Echographic tissue characterization in diffuse parenchymal liver disease: correlation of image structure with histology.

Seventy livers were examined in vitro using a computerized ultrasound B-mode data acquisition and analysis system. For tissue characterization, statistical parameters from pattern recognition algorithms describing image brightness and image structure were used. Reference classification based on histopathology as well as on chemical/morphometrical analysis led to the diagnostic classes of normal, fatty liver, fibrosis/cirrhosis and fatty fibrosis/cirrhosis. Comparing the two reference methods for ultrasound tissue characterization, reclassification based on chemical/morphometrical analysis resulted in a significant increase in diagnostic accuracy. The strong correlations between statistical ultrasound image parameters and morphometrical features reflect the relevance of our statistical approach to ultrasound tissue characterization.

Fatty Liver↗
PubMed1990

Computerized ultrasound B-scan texture analysis of experimental fatty liver disease: influence of total lipid content and fat deposit distribution.

Statistical pattern recognition procedures allow a quantitative description of ultrasound-B-scan image texture. According to well-established animal models, different types of fatty liver disease were induced in female Wistar rats. For the correlation of the computerized ultrasound image with its underlying histology a variable tissue model based on histomorphological data, texture analysis of the histological image and biochemical measurements of total lipid, water and hydroxyproline content was created. Whereas a regional arrangement of large fat deposits leads to a significant increase in the "mean grey level" (measure of image brightness) of the ultrasound-B-scan image, there is no difference in image brightness between normal liver tissue and liver steatosis for the tissue model with diffuse homogeneous fatty infiltration. It is demonstrated by multiple linear regression analysis that the "mean grey level" of the ultrasound-B-scan image depends not only on total lipid content but even more on the histomorphological fat deposit distribution.

Animals↗
PubMed1989

Phase-I trial of intravenous continuous infusion of tumor necrosis factor in advanced metastatic carcinomas.

Fifteen patients with advanced metastatic adenocarcinomas were treated in a phase-I study with continuous intravenous 24 h infusion of recombinant tumor necrosis factor alpha (TNF-alpha) in order to determine the maximum tolerated dose (MTD) and associated side-effects. Patients received 40-400 micrograms/m2 TNF-alpha once (arm A) or twice (arm B) weekly for a scheduled treatment period of 2 months. The observed systemic side-effects resembled those reported for interferons and included fever, chills, fatigue, headaches, myalgias, thrombocytopenia, prostration, and malaise. Dose-limiting toxicities, resulting in a median MTD of 200 micrograms/m2 for 24 h, were fever, chills, fatigue, myalgias, and thrombocytopenia. Out of 15 patients, 11 showed tumor progression, and 3 sustained in no change for over 2 months of treatment. A minor response was seen in 1 patient with a colorectal carcinoma and liver metastases. To reduce side-effects, patients were treated either with paracetamol or indomethacin. Higher MTDs were observed in patients treated with indomethacin. No detectable plasma TNF-alpha levels or TNF antibodies were measured under therapy (plasma TNF-alpha less than 20 pg/ml). We conclude that TNF-alpha appears to have some antineoplastic activity in patients with adenocarcinomas since 4 patients remained in no change or showed a minor response.

Antibodies↗
PubMed1989

Tumour necrosis factor production and natural killer cell activity in peripheral blood during treatment with recombinant tumour necrosis factor.

Tumour necrosis factor (TNF) has been found to be an important immunomodulator. Among other functions TNF activates natural killer (NK) cells and stimulates monocytes/macrophages in an autocrine fashion. TNF production and NK activity in peripheral blood mononuclear cells were determined in a clinical phase I study in which recombinant human (rh) TNF was administered as a continuous infusion weekly for a period of 8 weeks. Even though TNF production and NK activity were significantly reduced directly after rhTNF infusion the effect proved to be transient and most pronounced at the first rhTNF administration. One day after completion of the rhTNF infusion the peripheral cells released more TNF into the supernatant compared to TNF activity immediately before the rhTNF infusion. This effect was conspicuous in non-stimulated cultures. After repeated rhTNF infusions both stimulated and non-stimulated TNF production of the peripheral blood mononuclear cells was increased. NK cell activity was also enhanced after repeated cycles of rhTNF administration as compared to early rhTNF treatment. Thus, repeated rhTNF infusions lead to a stimulatory effect on TNF production and NK activity of peripheral blood cells.

Adult↗
PubMed1989

[Quantitative studies on the influence of connective tissue and fatty structures on the ultrasonic image of the liver].

Using a computerized ultrasound system, 63 autopsied livers were examined. A quantitative description of the ultrasound image was made by using statistical parameters from pattern recognition algorithms. As a reference a chemical/morphometrical classification into normal, diffuse and regional fatty infiltration and fibrosis/cirrhosis was performed. Diagnostic accuracy varied from 77% to 92%. Ultrasound tissue characterisation showed an influence of fatty and connective tissue structures on image parameters. This supplies evidence for the fact that computerised ultrasound examination yields more information from the ultrasound image than the normal observer. This may be the cause of an increased diagnostic accuracy when using computerized ultrasound systems, especially in the case of fibrosis/cirrhosis.

Diagnosis, Computer-Assisted↗
PubMed1989

[Computer-assisted ultrasonic B-scan texture analysis of experimental liver tumors].

Primary liver cancer has been induced experimentally in female Wistar rats by diaminoazobenzene intoxication or subcapsular liver implantation of Novikoff cell suspensions. The ultrasonic B-scan image of these malignant tumours are described via statistical texture parameters in respect of image brightness, microtexture and macrotexture. A discrimination of the tumour texture profiles is possible with an accuracy of about 80%. There are correlations between ultrasonic image parameters and histomorphological tissue components but there is no specific link between the histological tumour-type and these B-scan data.

Animals↗
PubMed1989

Intrahepatic 5-FU retreatment of liver metastases of colorectal cancer that were progressive under previous systemic chemotherapy.

Sixteen patients with liver metastases of colorectal cancer that were progressive under systemic chemotherapy were treated by hepatic arterial infusion therapy. 5-fluorouracil (5-FU) with a daily dosage of 1 g/m2/day was given continuously for 5 consecutive days at 3-week intervals. Restaging after three cycles of treatment revealed three partial remissions (PRs) and five patients with stable disease (SD). Duration of response was a median 17 months in patients with PRs. Survival time of the total group of patients was 11.6 months. Patients with PRs had 19 months, patients with SD 13 months, and patients with progressive disease 9 months median survival time. In 12 of the patients, tumor growth was limited to the liver for a long period of time, and extrahepatic metastases occurred in the end-stage disease. Therefore, in patients with progressive liver metastases of colorectal cancer under systemic chemotherapy and with no extrahepatic metastases, intrahepatic arterial chemotherapy may offer a further chance for tumor control.

Adenocarcinoma↗
PubMed1988

Decrease of natural killer cell activity and monokine production in peripheral blood of patients treated with recombinant tumor necrosis factor.

Tumor necrosis factor (TNF), a protein predominantly produced by activated macrophages/monocytes, is presently available in recombinant, purified form for clinical trials. Intensive studies in many laboratories have shown that besides the tumorcytotoxic effects, TNF acts on a large array of different cells and has potent immunomodulatory activities. In a clinical phase I study, some immunologic functional parameters of blood cells from patients who received 24-hour infusions of recombinant human TNF (rhTNF) were analyzed. Natural killer (NK) cell activity, TNF production, interleukin-1 (IL-1) production and mitogen-induced proliferation were measured either in whole blood samples or in cultures of peripheral mononuclear leukocytes of the patients directly before and after rhTNF infusion. NK cell activity, TNF and IL-1 production capacity and proliferative responses to concanavalin A (Con A) were significantly reduced after rhTNF application. We conclude from these observations that rhTNF in vivo acts directly or indirectly on NK cells and monocytes by either inactivating their functional capacity or by absorbing the relevant cells to the endothelial cell layer, thus removing them from circulation.

Adult↗
PubMed1984

[Gray-level histogram analysis in the sonographic diagnosis of diffuse parenchymal liver disease].

Increased echogenicity is one of the major diagnostic criteria for the subjective evaluation of liver echograms. In our approach to ultrasonic tissue characterisation by B-scan image analysis echogenicity is expressed by parameters deriving from the grey-level histogram. In this study the grey level histograms of a group of normals and patients with diffuse parenchymal liver disease are analysed. When employing the two parameters mean grey level (G) and standard deviation of grey levels (SG) the diagnostic accuracy was 90% (specificity 95%, sensitivity 85%). For subjective evaluation the liver echograms of a randomly selected sub-group of normals and patients were blindly evaluated by three observers who positively correlated the finding of increased echogenicity with the diagnosis of a pathological liver echogram. As demonstrated by our results the two-parameter analysis of the grey-level histogram leads to a quantification of the subjective diagnostic criterion of echogenicity, thus providing useful information for image interpretation.

Color↗
PubMed1983

[Sonographic diagnosis in primary cancer of the liver].

The sonographic findings and their contribution to differential diagnosis and tumor staging are described in 34 patients with hepatocellular carcinoma and in 12 cases of cholangiocellular carcinoma. In most cases of hepatocellular carcinoma the liver was diffusely involved at presentation, whilst in cholangiocarcinoma tumor growth was usually limited to a single lobe. Over 60% of the hepatocellular carcinomas were predominantly echogenic. The cholangiocarcinomas all presented with a highly echogenic tumor in combination with uni- or bilaterally dilated intrahepatic bile ducts. In 20 patients estimation of liver size by the ultrasound-measurement of liver span in the right midclavicular line is compared with ultrasound-measured liver volume and its value in assessing response to therapy. Volume changes in response to therapy were demonstrated in five patients with hepatocellular carcinoma. In alpha-fetoprotein positive tumors they corresponded with changes in alpha-fetoprotein levels.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Ultra-high-dose lanreotide treatment in patients with metastatic neuroendocrine gastroenteropancreatic tumors.

BACKGROUND: Symptomatic control and occasionally even tumor regression of functional neuroendocrine tumors (NET) of the gastroenteropancreatic (GEP) system can be achieved by somatostatin analogues. Assuming a dose-dependent antiproliferative effect of somatostatin analogues, we performed a study with the somatostatin analogue lanreotide in ultra-high dosages in patients with progressive, metastatic GEP NET. PATIENTS AND METHODS: 30 patients with metastatic GEP NET, progressive during treatment with somatostatin analogues (< or =1.5 mg/day) and/or interferon-alpha, underwent ultra-high-dose lanreotide therapy (5 mg lanreotide s.c. three times a day). Tumor growth was evaluated every 3 months. Serum chromogranin A, serum serotonin as well as urinary 5-hydroxyindoleacetic acetic acid levels were also determined at 3-month intervals. In patients with functional tumors, tumor-related symptoms were documented. RESULTS: After a 1-year treatment period with ultra-high-dose lanreotide, 1 complete and 1 partial remission were observed in patients with functional midgut NET. Eleven patients had stable disease and 11 patients showed continuing tumor growth after 3-12 months of treatment. Symptoms decreased significantly during therapy. CONCLUSIONS: Our data show that ultra-high-dose lanreotide treatment in patients with metastatic GEP NET can lead to control of both symptoms and proliferation in at least some patients refractory to conventional therapies.

Antineoplastic Agents↗
PubMedDate not supplied

Role of ondansetron plus dexamethasone in fractionated chemotherapy.

This randomised, double-blind, parallel-group study was carried out to compare the efficacy and safety profile of ondansetron plus dexamethasone and metoclopramide plus dexamethasone in patients receiving fractionated cisplatin (20-25 mg/m2/day) chemotherapy for the treatment of testicular cancer. An interim analysis of 95 patients showed that the ondansetron regimen was significantly superior compared to the metoclopramide regimen (p < 0.001). According to the study protocol the study was terminated at this stage. At the time the decision to stop the study was taken, a total of 113 patients had been enrolled and were evaluable on an 'intention to treat' basis. Fifty-six of these had received ondansetron (32 mg i.v. single dose/day) plus dexamethasone (20 mg i.v. single dose/day) and 57 were given metoclopramide (2 mg/kg or 1 mg/kg i.v. twice a day) plus dexamethasone (20 mg i.v. single dose/day). The ondansetron regimen was significantly superior in the control of emesis and nausea. Seventy-one percent of patients experienced 2 or fewer emetic episodes over the entire 5-day study period compared with 26% of patients given metoclopramide (p < 0.001). Seventy-nine percent of patients in the ondansetron group experienced 'none' or only 'mild' nausea compared with 39% of patients in the metoclopramide group (p < 0.001). The dose of metoclopramide had to be reduced during the study from 2 mg/kg i.v. twice daily to 1 mg/kg i.v. twice daily because 4 of the first 8 patients randomised to this treatment experienced extrapyramidal reactions. Ondansetron was well tolerated and it did not induce any extrapyramidal reactions. The results of this study show that ondansetron plus dexamethasone represents a very effective treatment option for patients receiving fractionated cisplatin chemotherapy for testicular cancer.

Adolescent↗