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Biomedical subjects

L Hafström

Publications and source records attributed to L Hafström.

At least 37 records · Page 2Linked to original sources
PubMed1994

Histamine in immunotherapy of advanced melanoma: a pilot study.

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.

Adult↗
PubMed1994

125I-labelling of an internally 75Se-labelled monoclonal antibody--biodistribution in tumour-bearing nude mice.

A monoclonal antibody, C215, was first internally labelled with 75Se-methionine and then labelled with 125I. The biodistribution of the dual-labelled [125I][75Se]C215 was studied in tumour-bearing nude mice killed 3 days after injection. The biodistribution of the dual-labelled [125I][75Se]C215 was compared with the biodistribution of single-labelled [131I]C215 and [75Se]C215. Iodine-labelled antibodies seem to be damaged during iodination, affecting the disappearance rate and tumour uptake. There were no signs of dehalogenation of circulating antibodies or antibodies taken up in the tumour.

Adenocarcinoma↗
PubMed1994

Hepatic artery occlusion and energy charge in rat liver tumour.

Hepatic artery ligation (HAL) is a model for inducing a vascular attack on liver tumours which causes a reduction in tumour growth. To determine in an experimental rat liver adenocarcinoma the duration and magnitude of changes in adenonucleotide concentration and energy charge (EC) after HAL, analyses of energy-rich nucleotides were performed at 1, 2, 24 and 168 hours after HAL or a SHAM procedure. There was a significant decrease of the ATP content and energy charge in the tumour one hour after HAL. Two hours after HAL this difference had decreased and with longer observation it was not detectable. Twenty-four hours of starvation did not significantly alter the effects of HAL on the tumour. HAL gives rise to a transient energy depletion of the tumour which is not completely compensated for by glycolysis after 1 hour, but is restored after 2 hours.

Adenocarcinoma↗
PubMed1994

Whole body energy expenditure protein breakdown and polyamine excretion during high dose treatment with interleukin-2 and interferon-alpha.

OBJECTIVE: To correlate changes in whole body resting energy expenditure and protein breakdown with the production of stress hormones, excretion of polyamines, and circulating concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha), in patients undergoing treatment with high doses of interleukin-2 (IL-2) and interferon-alpha (IFN-alpha). DESIGN: Prospective open study. SETTING: University Department of Surgery. SUBJECTS: 11 Patients with malignant melanoma (n = 8) or renal cell carcinoma (n = 3) all of whom had a Karnofsky score of 80 or more. INTERVENTIONS: Daily intravenous infusion of IL-2 (18 x 10(6) IU/m2/day) and subcutaneous injection of IFN-alpha (3 x 10(6) IU/m2/day) for days 1-5 and 8-12 in two courses with a three week interval. MAIN OUTCOME MEASURES: Energy expenditure measured by indirect calorimetry, body temperature, heart rate, urinary excretion of amino acids and nitrogen, and plasma cytokine concentrations. RESULTS: Three patients had a partial response. IL-1 was not detectable in plasma; and concentrations of IL-2 increased rapidly during the infusion before falling rapidly when it stopped, of IL-6 increased significantly (mean (SEM) 3.44 (1.6) to 11 (2) U/ml, p < 0.05), and of TNF-alpha increased by 295% (p < 0.05). Resting energy expenditure increased from 92 (4) to 113 (4) kJ/kg/day (p < 0.001) during the infusion and this was accompanied by a rise in temperature and an increase in the urinary excretion of cortisol (which also correlated with increased breakdown of whole body protein). CONCLUSION: The increased energy expenditure and protein breakdown were probably a result of stimulation of production of catecholamines and cortisol, as after injury, but the direct effects on temperature regulating neurons may be important.

Aged↗
PubMed1993

Regional lymphatic drug exposure following intraperitoneal administration of 5-fluorouracil, carboplatin, and etoposide.

Intraperitoneal (i.p.) administration of chemoterapeutic agents results in greater total drug exposures in the peritoneal cavity than in plasma. A study on the drug exposure for i.p. lymphatics of pigs, receiving 5-fluorouracil (5-FU), etoposide (VP-16) and carboplatin (CBDCA) by the i.p. route was conducted. Drug concentrations in peritoneal fluid, plasma, and thoracic duct lymph were monitored over the ensuing 3 h. 5-FU appeared rapidly in thoracic duct, lymph and plasma. The lymph concentration declined after 20 min while the plasma concentration remained stable. CBDCA reached a stable concentration in lymph and plasma after 60 min. VP-16 peaked in the lymph after 20 min, whereas the plasma concentration continued to rise for 150 min; the peritoneal half-life for VP-16 was too long for clearance to be defined. Total drug exposure (AUC) was for 5-FU 5.7-fold greater for lymph than for plasma and for CBDCA equal in both compartments. VP-16 had a 2.1-fold higher AUC for lymph than for plasma. The results indicate that the i.p. route of administration results in a greater exposure of the lower thoracic duct lymph than the plasma to 5-FU, produces only a marginally increased exposure to VP-16, and results in no difference for CBDCA. The efficacy of 5-FU is a function of total drug exposure. The results reported provide a strong rationale for evaluating the adjuvant use of i.p. 5-FU in colorectal and gastric carcinoma.

Animals↗
PubMed1993

Therapy with 125I-labelled internalized and non-internalized monoclonal antibodies in nude mice with human colon carcinoma xenografts.

The therapeutic effects of 125I-labelled (18-97 MBq) monoclonal antibodies (MAb) C-242, C-215 and S-S.1 were studied in nude mice with human colorectal adenocarcinoma tumours. The antibodies were administered 2 or 10-16 days after implantation of the tumour cells. The monoclonal antibody C-242 was internalized into the tumour cells, C-215 was internalized to a lower degree while S-S.1 (unspecific MAb) was not internalized at all. No enhanced therapeutic effect of 125I-C-242 was observed, as a result of Auger electrons, compared with 125I-C-215 and 125I-S-S.1.

Adenocarcinoma↗
PubMed1993

Energetics of nutrition and polyamine-related tumor growth alterations in experimental cancer.

The aim of this study was to evaluate whether food intake modulates experimental tumour growth by acute alterations in the energy state and blood flow of the tumour, and if so whether such changes are related to alterations in the enzyme ornithinedecarboxylase (ODC) and DNA synthesis. Inbred mice (C57BL/J) bearing a syngeneic undifferentiated and rapidly growing tumour were used. The tumour levels of high energy phosphates were measured in vivo by 31-P-NMR spectroscopy and biochemically following tissue extraction. DNA synthesis was estimated by measuring the incorporation of bromodeoxy-uridine into tumour DNA. Difluoro-methylornithine (DFMO) was used to inhibit ODC-activity. Tumour blood flow was estimated by a 132Xe local clearance technique. Tumour progression was associated with a significant decrease in tumour tissue high energy phosphates. Acute starvation decreased DNA-synthesis and tumour energy charge as well as its PCr/Pi which were rapidly normalised during subsequent refeeding. These changes were related to similar alterations in tumour blood flow. The inorganic phosphate (Pi) resonance and the resonances in the phosphomonoester (PME) region were considerably increased in tumour tissue. Inhibition of ODC-activity by DFMO decreased DNA-synthesis, which was associated with a secondary increase in tumour high energy phosphates probably due to a lowered energy demand for tumour cell division. The results demonstrate that host undernutrition was translated into retarded tumour growth associated with a decrease in the energy state and blood flow of the tumour. The results have bearing for the evaluation and planning of all treatment protocols with potential influence on food intake in experimental tumour-bearing animals.

Adenosine Triphosphate↗
PubMed1992

Isolated hyperthermic liver perfusion with cytostatic-containing perfusate activates the complement cascade.

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.

Adult↗
PubMed1992

The influence of hepatic artery ligation and of vasopressin on liver tumour blood flow in rats.

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.

Animals↗
PubMed1992

Comparison of the biodistribution of 75Se- and 131I-labelled monoclonal antibodies in nude mice.

A monoclonal antibody, C-215, against colon cancer, was internally labelled with [75Se]methionine. The biodistribution was studied in tumour-bearing nude mice and compared with the biodistribution of [131I]C-215. The tissue uptake was divided into three parts: antibody bound to the antigen, antibody in the extracellular space and uptake of the released radionuclide. [75Se]C-215 showed a greater amount of antigen-bound antibody in the tumour, but also a greater unspecific uptake both in tumour and normal tissue.

Animals↗
PubMed1991

Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities. Swedish Melanoma Study Group.

A prospective randomized trial testing regional hyperthermic perfusion with melphalan has been conducted. Sixty-nine patients with recurrent malignant melanoma of the extremities were randomly allocated to surgery (36 patients) or surgery plus regional perfusion (33 patients). Prognostic variables concerning primary tumor as well as the recurrent disease were evenly distributed in the groups, excluding any bias in the randomization. Median tumor-free survival after randomization was 17 months in the perfusion group and 10 months in the control group. There were 15 locoregional recurrences in the perfusion group and 24 in the control group. The tumor-free survival curve was significantly (P = .044) better for the perfusion group than for the control group. Median survival time after randomization was 57 months in the perfusion group and 35 months in the control group. This difference was not significant. One patient died within 1 month after perfusion of pulmonary embolism. Regional hyperthermic perfusion after surgery of recurrent malignant melanoma should only be recommended in prospective and controlled trials, until its value has been proven in several randomized studies.

Adult↗
PubMed1991

Macrophage function and surgery. A clinical review with special reference to phagocytosis.

Present knowledge of macrophage phagocytosis in the context of surgical trauma is reviewed. The historical and morphologic background of the reticuloendothelial system and the mononuclear phagocyte system is surveyed. The physiology of the phagocytic process and methods of measurement are summarized and the influence on phagocytosis of shock, sepsis, cancer, parenteral nutrition and surgical procedures such as liver resection and splenectomy is discussed. Conclusions are that multiple factors may depress macrophage phagocytosis during surgery and that, in order to maintain immune defence balance, traumatic manipulation of tissue and abdominal organs must be minimized.

Humans↗
PubMed1991

Aggregation of microspheres in blood flow measurements.

The aggregation of NEN-TRAC radionuclide-labeled 15 microns resin microspheres was studied in vitro and in vivo. In vitro, the control group not agitated at all was compared with groups subjected to agitation with a Vortex Shaker or agitation with first a Vortex shaker and then a sonification bath. Loading the microspheres in a catheter made agitation unnecessary (5.6 +/- 1.7 aggregates/100 spheres and 2.3 +/- 0.5 microspheres/aggregate). Sonification increased aggregation when the solution was drawn into 1 cc syringes (13.7 +/- 2.6 aggregates/100 spheres and 2.8 +/- 1.2 microspheres/aggregate). In vivo less aggregates were observed. Loading the microspheres into PK 50 catheters and then injecting them into the left ventricle of the heart after agitation in a Vortex shaker for 1 min minimized aggregation (1.6 +/- 1.0 aggregates/100 spheres and 2.2 +/- 0.4 spheres/aggregate). Sonification increased both the number of aggregates and the number of spheres in each aggregate significantly (10.0 +/- 3.1 aggreates/100 spheres and 2.8 +/- 1.3 spheres/aggregate). Aggregates of 10 to 40 microspheres were occasionally observed. When the microspheres were injected into the aorta at the level of the diaphragm, one large aggregate (approximately 50 spheres) was seen. The handling of the microsphere solution is important to prevent aggregation and the treatment recommended by the manufacturer does not seem to be the optimal. Large aggregates, which are rare, might embolize the precapillary arteries. Small aggregates are more common and they might result in disproportionately fewer microspheres in vessels than their actual blood flow. This would make the microsphere method less reliable in blood flow measurements.

Animals↗