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- Naredi, Peter, 1955, et al.
(author)
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Evaluation of blood flow measurements with microspheres and rubidium--an experimental study in rats.
- 1990
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In: International journal of microcirculation, clinical and experimental / sponsored by the European Society for Microcirculation. - 0167-6865. ; 9:4, s. 423-37
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Journal article (peer-reviewed)abstract
- The microsphere method has been widely used for blood flow measurements in normal and tumour tissues. The microsphere method was evaluated for repeated measurements of cardiac output and regional blood flow in anesthetised rats and in anesthetised rats given noradrenalin and thereby having altered haemodynamics with special emphasis on liver blood flow. Comparing the microsphere method with the soluble indicator method (86Rubidium) gave equal cardiac output values. The liver blood flow was lower and the spleen blood flow was higher with the microsphere method. Two microsphere injections at 10 min intervals were performed on anesthetised rats. In one group 817 +/- 10(3) microspheres were injected each time, in a second group 436 +/- 10(3) and in a third noradrenalin was added and then 430 +/- 10(3) microspheres injected twice. There was good reproducibility for cardiac output and for most organ and tissue blood flows between first and second microsphere injection. No influence on arterial liver blood flow was seen. A blood pressure fall and a decreased heart rate was registered after the first injection in the group given 817 x 10(3) spheres. There was also a blood pressure fall in the group given noradrenalin after the first microsphere injection. The microsphere method with two injections of 436 x 10(3) microspheres seems adequate to use in arterial blood flow studies of the liver and simultaneous cardiac output measurements.
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| 2. |
- Naredi, Peter, 1955, et al.
(author)
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The influence of hepatic artery ligation and of vasopressin on liver tumour blood flow in rats.
- 1992
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In: Journal of surgical oncology. - : Wiley. - 0022-4790 .- 1096-9098. ; 50:2, s. 70-6
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Journal article (peer-reviewed)abstract
- The blood flow in an experimental adenocarcinoma in the rat liver was determined with the 133Xe-washout technique before and after hepatic artery ligation (HAL). There was an initial reduction of the washout of 50%. This was further reduced after 1 day by 50%, which was maintained for 7 days. Seven days after HAL or sham procedures the 133Xe-washout was of similar magnitude in the liver tumours, although after the sham procedure the tumours were larger (3.4 g vs. 1.5 g). The estimated tumour blood flow was then approximately 0.04 ml x min-1 x g-1. The influence on normal liver parenchyma of HAL was a reduction at 30 minutes, which was maintained for 7 days. Postacton--a synthetic vasopressin--did not influence the 133Xe-washout in normal liver parenchyma in non-tumour, as well as in tumour-bearing animals. There was no influence of Postacton on the 133Xe-washout in the liver tumours. Thirty minutes after HAL Postacton gave a reduction of blood flow in normal liver parenchyma of tumour-bearing animals, which is thus only from the portal vein. In tumours Postacton did not significantly reduce the tumour blood flow immediately after HAL.
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| 3. |
- Arnestad, J P, et al.
(author)
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Isolated hyperthermic liver perfusion with cytostatic-containing perfusate activates the complement cascade.
- 1992
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In: The British journal of surgery. - 0007-1323. ; 79:9, s. 948-51
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Journal article (peer-reviewed)abstract
- Eight patients with advanced liver malignancy undergoing isolated hyperthermic liver perfusion with melphalan and cisplatin were studied with regard to complement activation and formation of anaphylatoxins (C3a and C5a) and terminal C5b-9 complement complexes (TCCs). Blood samples for complement variables (C1-INH, C3, C4, C5, C3a, C5a and TCCs) were taken before surgery, 1 min before the start of perfusion, 1, 2 and 3 h after the start of perfusion, and 24 h after operation. Samples were drawn from the perfusate 1 h after the start of perfusion. Activation of complement was observed during perfusion. Raised plasma concentrations of C3a and TCCs were recorded and high levels of C3a and TCCs were found in the perfusate. In vitro tests indicated that melphalan and cisplatin may activate complement. This activation occurred at 37 and 42 degrees C but was more pronounced at 42 degrees C.
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| 4. |
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| 5. |
- Hafström, Lars-Olof, 1936, et al.
(author)
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Isolated hyperthermic liver perfusion with chemotherapy for liver malignancy.
- 1994
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In: Surgical oncology. - 0960-7404. ; 3:2, s. 103-8
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Journal article (peer-reviewed)abstract
- In an open study of unresectable liver tumours, isolated regional perfusion with hyperthermia and cytotoxic drugs has been tested in 29 patients. Four patients had primary hepatocellular cancer, 10 patients had metastases from malignant melanoma, remaining from breast cancer, colorectal cancer, midgut carcinoids and miscellaneous primaries. At laparotomy the proper hepatic artery and portal vein were canulated and connected to a pump oxygenator. The inferior vena cava was canulated with a triple lumen catheter (Perfufix) allowing for porto-caval shunting, drainage of lower body and renal veins to the heart and separate drainage of liver veins to the pump oxygenator. Liver perfusion was performed with a mean flow of 900 ml per min. Melphalan and cis-platinum 0.5 mg/kg body-weight were added to the perfusate for 1 h after liver temperature reached 40 degrees C. Four patients died within 30 days of perfusion due to multiple organ failure. These patients had more than 50% of liver volume occupied by cancer. All surviving patients developed reversible hepato- and renal toxicity. Partial tumour regression was registered in 20% of the patients. Five patients have survived more than three years. Hyperthermic liver perfusion is feasible but in patients with massive liver tumour, there is a significant risk of developing multiple organ failure.
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| 6. |
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| 7. |
- Hellstrand, Kristoffer, 1956, et al.
(author)
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Histamine in immunotherapy of advanced melanoma: a pilot study.
- 1994
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In: Cancer immunology, immunotherapy : CII. - 0340-7004. ; 39:6, s. 416-9
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Journal article (peer-reviewed)abstract
- Sixteen patients with advanced metastatic malignant melanoma were treated with a high-dose infusion of interleukin-2 (IL-2; 18 x 10(6) IU/m-2 day-1) together with daily subcutaneous (s.c.) injections of interferon alpha (IFN alpha; 3 x 10(6) U/m-2 day-1) in 5-day cycles. Nine of these patients were given histamine (1 mg s.c.) twice daily during treatment with IL-2 and IFN alpha. In the seven patients who did not receive histamine, one partial response (that is a reduction of more than 50% in the total tumour burden) was observed in a patient with skin and lymph node melanoma. In the eight histamine-treated patients evaluable for response, four partial responses were observed. Two other patients showed regression at one site of metastasis but tumours remained unchanged at other sites. Two histamine-treated patients showed complete resolution of extensive liver metastasis. Sites of response in histamine-treated patients also included the subcutis, lymph nodes, skeleton, spleen and muscle. Lung melanoma did not respond to histamine/IL-2/IFN alpha. Three patients with lung tumours responded with significant (more than 50%) reduction of the volume of soft-tissue tumours, suggesting that the response to histamine may be organotropic. Survival was significantly prolonged in patients receiving histamine. Our data suggest that treatment with histamine may improve the antitumour efficacy of immunotherapy in metastatic melanoma.
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| 8. |
- Holmberg, Stig B, 1946, et al.
(author)
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Cytotoxicity of liver macrophages against liver tumours. Influence of betamethasone, indomethacin and allopurinol.
- 1991
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In: Anticancer research. - 0250-7005. ; 11:5, s. 1827-30
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Journal article (peer-reviewed)abstract
- Macrophage activation with zymosan has an inhibitory effect on tumour take and initial tumour growth in the rat liver. 91 rats with syngeneic transplanted hepatoma in the liver were treated with zymosan (46) or saline (45). Betamethasone (glucocorticoid), indomethacin (prostaglandin synthesis inhibitor), allopurinol (oxygen radical scavenger) or saline were administered concomitantly. Tumour take, tumour growth and relative spleen weight were used as in vivo parameters of liver macrophages cytotoxicity and general macrophage activation. Zymosan inhibition of tumour take was counteracted by betamethasone, indomethacin and allopurinol. Betamethasone increased the growth rate of the non-zymosan treated tumours during seven days. Indomethacin decreased the growth rate of the tumours in non-zymosan treated rats up to 14 days. Allopurinol significantly blocked the zymosan inhibition of tumour take and tumour growth after 7 and 14 days. Allopurinol blocked zymosan induced increased relative spleen weight. It is proposed that the liver macrophage cytotoxicity induced by zymosan is in part mediated via production of oxygen radicals.
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| 9. |
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| 10. |
- Lindnér, Per, 1956, et al.
(author)
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Biochemical modulation of intraperitoneal fluorouracil by allopurinol-the effect on an experimental adenocarcinoma in the liver.
- 1994
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In: Anticancer research. - 0250-7005. ; 14:3A, s. 847-52
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Journal article (peer-reviewed)abstract
- In a rat liver tumour system with a nitrosoguanidine-induced carcinoma and in an in vitro system with the same tumour, the effect of allopurinol on the toxicity and antitumour effect of 5-fluorouracil (5-FU) was explored. Two doses of 5-FU, 30 and 60 mg/kg b.w. intraperitoneally (i.p.), were tested with a large dose of allopurinol subcutaneously (s.c.( (300 mg) in rats. The drugs were given for three consecutive days. The lethal toxicity of 60 mg 5-FU i.p. could not be counteracted by allopurinol. Allopurinol and 30 mg 5-FU reduced the tumour growth rate more than 5-FU alone. The spleen was smaller, as a sign of increased toxicity, without allopurinol. The concentration of allopurinol and its metabolites in the general circulation was high. In vitro, there was no additive or specific effect of allopurinol. These results indicate some in vivo metabolic modulation of 5-FU efficacy by allopurinol if 5-FU is administered intraperitoneally and allopurinol systemically.
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