PubMed Health⌕ Search

Biomedical subjects

L Hafström

Publications and source records attributed to L Hafström.

At least 73 records · Page 4Linked to original sources

Increased urinary polyamine excretion during liver regeneration.

Tumor growth is a process associated with both cell proliferation and cell death. The increase in polyamine excretion observed in cancer patients may be partly due to leakage of polyamines from proliferating cells, which all contain an elevated polyamine level. However, the increased polyamine excretion may also be due to a release of polyamines from dead or damaged cells. To determine if actively proliferating cells release polyamines, the urinary polyamine excretion was measured during a proliferative event associated with minimal cell necrosis. Rats subjected to partial hepatectomy were used as an experimental model. Their 24-hr urines were collected during 6 consecutive days following the operation. Rat liver regeneration is characterized by a proliferation wave with a maximum 24 hr after the operation. The 24-hr urinary putrescine excretion reached a maximum 2 days after the operation and then decreased. The 24-hr urinary spermidine excretion increased during the second day following operation and remained essentially unchanged during the rest of the experimental period. Although there is an apparent correlation between elevated urinary polyamine excretion and the proliferative activity, concurrent permeability changes and necrotic events may contribute to the increase in polyamine excretion.

Animals↗

A randomized trial of oral 5-fluorouracil versus placebo as adjuvant therapy in colorectal cancer Dukes' B and C: results after 5 years observation time.

A double-blind randomized trial of daily oral 5-fluorouracil (5 mg kg-1 bodyweight) for 3 months versus placebo as adjuvant therapy to surgical treatment of colorectal cancer Dukes' B and C was conducted. In total 421 patients were randomized; 198 patients with Dukes' B, 159 with Dukes' C and 64 were referred to a limited resection group. The distribution of prognostic variables was similar in both groups indicating the absence of any bias and the efficacy of the randomization. Disease-free interval and survival time were analysed as end points. After 5 years of follow-up of all patients there was no significant difference between treatment or placebo group in the total material or the subgroups regarding either of the end points. There was no difference in localization of first recurrence between treated and control group. A high withdrawal of therapy was found in the 5-FU group (40 per cent) and in the placebo group (13 per cent).

Clinical Trials as Topic↗

Value of liver scintigraphy in pretreatment staging and in follow-up of patients with malignant melanoma.

Liver scintigraphy (99Tcm sulphur colloid) was performed in 118 patients with malignant melanoma. In 73 patients diagnosed as stage I, the pretreatment evaluation showed one false-negative and one false-positive examination. During follow-up there were ten abnormal liver scintigraphies; one was later correlated to liver metastases. In 46 patients diagnosed as stage II-IV, the pretreatment liver scintigraphy yielded false-negative results in 36% and false-positive results in 15%. The predictive values of positive and negative tests were 44% and 81%, respectively. The yields of liver tests (S-alkaline phosphatase, S-gamma-glutamyl-transferase) in patients with liver metastases were low. This study demonstrated the limitations of liver scintigraphy for diagnosis of liver metastases in patients with malignant melanoma.

Evaluation Studies as Topic↗

Local hyperthermia in treatment of experimental liver tumors.

An experimental model for local microwave hyperthermia treatment of liver tumors is presented. Fifty-four Wistar rats were inoculated with a transplantable adenocarcinoma (NGW) in the central liver lobe. Ten to 16 days later 28 of the rats were exposed to local hyperthermia. A master thermistor placed in the liver parenchyma adjacent to the tumor controlled the hyperthermia, and the tumor-bearing liver lobe was maintained at 42.0 degrees C for 1 hour. At laparotomy 7 days after treatment, the tumor volume was measured. Four weeks after tumor inoculation, autopsy was performed. The tumor and the surrounding parenchyma was excised for histopathologic examination. A statistically significant reduction in tumor growth was found after exposure to local hyperthermia, the effect of hyperthermia being most pronounced in moderate-sized tumors (300-500 mm3 or 0.5-0.75 g). In larger tumors (greater than 900 mm3 or greater than 1.1 g) extensive necrosis developed after hyperthermia treatment. This indicates good tumoricidal effect even in large tumors, although this is not obvious if reduction in tumor growth is used as the only parameter to evaluate the effect of hyperthermia.

Adenocarcinoma↗

Influence of a reticuloendothelial-suppressing agent on liver tumor growth in the rat.

Reticuloendothelial (RE) function was evaluated by measuring the biokinetics of a standardized 99Tcm-sulphur colloid. Methyl palmitate was administered intravenously on two consecutive days. A statistically significant reduction in the colloid uptake rate of the liver was registered after methyl palmitate administration. Histological examination revealed no signs of destruction of RE cells or microembolization. Inoculation of an experimental nitrosoguanidine-induced transplantable adenocarcinoma to the liver was performed in 16 rats one day after methyl palmitate administration and in 16 controls. Tumor size was significantly larger in methyl-palmitate-treated animals at 7 and 14 days after inoculation. Survival was significantly decreased in methyl-palmitate-treated rats. These rats showed signs of fatty vacuolization and necrosis of liver parenchyma earlier than controls. Analyses of beta-hexosaminidase and lactate dehydrogenase revealed no deviation of enzyme levels either before or after tumor inoculation. The results indicate that a temporary suppression of RE function at the time of tumor inoculation may influence subsequent tumor growth.

Adenocarcinoma↗

Lymphoscintigraphy in patients with malignant melanoma: a quantitative and qualitative evaluation of its usefulness.

Lymphoscintigraphy using 99mTcSb2S3 colloid was performed in 32 patients with malignant melanoma. Subcutaneous injections were made peritumorally in 20 patients and dorsopedally in 12 patients. Regional lymph node dissections were carried out on the following day in 16 patients and the resected lymph nodes were weighted, measured for radioactivity, and examined by light microscopy. Lymph flow to regional lymph nodes was shown in all but 2 patients. Twenty-nine of 239 lymph nodes contained metastases. Radioactivity was demonstrated in 17 of these nodes. In 5 of 11 patients with metastatic disease, the highest uptake was found in cancerous lymph nodes. The specific activity-uptake distribution in isolated ilio-inguinal lymph nodes after a dorsopedal injection was log-normal with a mean of 0.05%/g indicating a good saturation of colloid particles. This investigation concludes that the observed lymph flow directions in patients injected peritumorally are of value for the follow-up. Quantitative lymphoscintigraphy in patients with melanoma of the lower extremities is, however, of no value for excluding ilio-inguinal lymph node metastases.

Animals↗

Influence of hepatic artery ligation on survival. An experimental study in rats.

Interruption of the arterial blood supply to the liver has been used clinically for more than 15 years in patients with nonresectable liver tumors. The induced effect of hepatic artery occlusion on blood flow and metabolism has been studied extensively, whereas survival time has hardly been examined. Evidence of prolongation of survival after hepatic artery ligation, although not properly statistically analyzed, has been found in previous series of experimental animals, but the effect has not been established clinically. In this experimental study of rats with adenocarcinoma in the liver, a statistically significant prolongation of survival time was observed for the animals subjected to hepatic artery ligation when compared with untreated control animals. A statistically significant increase in body weight developed in all ligated animals during the experimental period, whereas the untreated control animals showed a statistically significant decrease in body weight.

Adenocarcinoma↗

Release of beta-hexosaminidase after administration of different agents affecting the reticuloendothelial system. An experimental study in rats.

Plasma levels of a lysosomal enzyme, beta-hexosaminidase (beta-N-acetylglucosaminidase, EC 3.2.1.30) were studied in Wistar rats after administration of 99mTc -sulfur colloid, 198Au colloid, gelatine (Haemaccel), alcohol, methylpalmitate and zymosan. The activity of beta-hexosaminidase was increased 10, 30 and 60 min after the zymosan injection. After 24 and 48 h, enzyme levels had returned to those at outset. The transient release of beta-hexosaminidase probably occurred only during the phagocytosis of zymosan which was evaluated by histological examination of lung, liver and spleen. After the injection of all other agents tested, no significant aberration of beta-hexosaminidase levels was seen. Activity distribution of the radio-labeled colloids revealed differences in organ uptake which were attributed to a difference in colloid particle size. Although the colloids tested have been used extensively for determination of reticuloendothelial function and histological studies suggest phagocytosis of the particles, their administration did not affect plasma beta-hexosaminidase levels. Since lysosomal enzymes are cleared from the blood predominantly by liver macrophages, the primary location of particle phagocytosis may explain the present findings.

Animals↗

Influence on plasma beta-N-acetyl-D-glucosaminidase of reticuloendothelial stimulation and depression: an experimental study in rats.

Plasma levels of the lysosomal enzyme, beta-N-acetyl-D-glucosaminidase (EC 3.2.1.30; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase ) were estimated 120 minutes after intravenous injection of zymosan in rats. Different groups of animals were investigated according to pretreatment with agents influencing reticuloendothelial activity. Pretreatment for two days with the reticuloendothelial stimulating agent, zymosan, or the reticuloendothelial suppressing agent, methyl palmitate, did not influence the basal plasma levels of beta-N-acetyl-D-glucosaminidase. In all groups after zymosan injection, plasma beta-N-acetyl-D-glucosaminidase activity was increased in comparison with basal levels. The increase of enzyme activity was most pronounced after pretreatment with zymosan and differed significantly from enzyme activity after pretreatment with methyl palmitate. Alcohol administration in combination with zymosan did not cause a further rise of beta-N-acetyl-D-glucosaminidase activity in normal rats nor in rats pretreated with zymosan. The observations suggest that plasma levels of beta-N-acetyl-D-glucosaminidase in rats after a standardized zymosan injection are related to the functional status of the reticuloendothelial system (RES).

Acetylglucosaminidase↗

Blood leakage and melphalan leakage from the perfusion circuit during regional hyperthermic perfusion for malignant melanoma.

In regional hyperthermic perfusion with melphalan for patients with malignant melanoma of the leg, plasma leakage between the perfusion circuit and the systemic circulation was 4-7 ml X min-1. The melphalan concentration in the perfusate was biphasic, with half-lives of 8-12 mins for the initial phase and 19-28 mins for the second phase, after the first dose. After a second dose, the corresponding values were 11-13 and 26-34 mins. The highest concentration in general circulation was 0.38 micrograms X ml-1.

Chemotherapy, Cancer, Regional Perfusion↗

The effect of total body microwave hyperthermia and hepatic artery ligation on liver tumors--an experimental study in rats.

The effect of general microwave hyperthermia and hepatic artery ligation (HAL) was tested on Wistar rats with a transplanted N-methyl-N-nitrosoguanidine-induced adenocarcinoma in the liver. Total body hyperthermia (41.5 degrees C for 1 hour, three times during 24 hours) was given on the same day as HAL, and 1, 2, and 3 days after. HAL induced a slower tumor growth than untreated controls. No additive effect was registered when total body microwave hyperthermia was added to HAL. When hyperthermia was added 2 days after HAL, there was a transient decrease in tumor volume as in the HAL series. Total body microwave hyperthermia added 3 days after HAL induced a faster tumor growth than after HAL alone. When hyperthermia was added the same day and 1 day after HAL, there was a 50% mortality.

Animals↗

Influence of hepatic artery ligation on liver tumor growth in rats.

Liver tumors, both primary and secondary, receive their main blood supply from the hepatic artery. Hepatic artery ligation (HAL) causes a reduction in tumor growth and tumor necrosis. In this experiment, three different experimental tumors were used to study the effect of hepatic artery ligation at different intervals after the occlusion of the arterial blood supply. Hepatic artery ligation causes a reduction in liver tumor growth for all three tumors but with some variation according to age and type of tumor.

Animals↗

Estimation of liver tumor volume using different formulas - an experimental study in rats.

Experimental solitary ellipsoid liver tumors in the rat can be induced by inoculation of a tumor-cell suspension of known potency into the liver parenchyma. During laparotomy, the largest (a) and the smallest (b) superficial diameters of the tumor were measured on the surface of the liver with vernier calipers. Four different formulas have been tested and compared with the actual volume from the extirpated tumor and tumor weight. Within the size range of 15-700 mm3, based on the calculation of the difference between logarithmic tumor volume from the different formulas versus logarithmic volume of extirpated and dissected tumors and regression analyses, volume of the unremoved liver tumor can be best calculated according to the formula V = a x b2/2.

Animals↗

Reticuloendothelial function in normal and tumor-bearing rats. Measurements with a scintillation camera technique.

The function of the reticuloendothelial system (RES) was evaluated after the inoculation of an experimental tumor in rats. Four groups were studied according to tumor size and site. Reticuloendothelial function was evaluated by measuring the biokinetics of a standardized [99Tcm]-sulfur colloid. Estimation of the uptake rate of the labeled colloid into the liver and other parts of the RES was performed through the use of a two-compartment model. Animals with small liver or subcutaneous tumors showed an increased activity of both the hepatic and the extrahepatic RES. Animals with large retroperitoneal tumors showed a significant decrease in the RE function of the liver. In these animals the function of the extrahepatic RES was not changed compared to controls but was, however, significantly decreased compared to animals with smaller tumors. The findings may reflect a difference in the impact of tumor size on RE function extra- and intrahepatically.

Animals↗

The effect on extrahepatic cancer of hepatic artery ligation: an experimental study in rats with liver tumors.

In three different tumor systems (sarcoma, hepatoma and adenocarcinoma) in rats, hepatic artery ligation (HAL) 10 days after tumor cell inoculation in the liver caused liver tumors which when measured 7 days later were statistically significantly smaller than those found in untreated control animals. The day before the experimental procedure the animals were challenged with tumor cell suspensions subcutaneously on the back. In the rats with the adenocarcinoma these subcutaneous tumors were larger in the HAL-group than in the control groups. The same results were obtained in the animals with the sarcoma. No such differences were observed in the rats with the hepatoma. To extrapolate these findings in a rat tumor system to the clinical situation in man should be done with extreme caution. There are subjective clinical impressions in man of a similar type, which may indicate common mechanisms. These findings could indicate that HAL should not be performed in patients with manifest extrahepatic tumor growth and only in controlled studies in patients with occult extrahepatic growth.

Adenocarcinoma↗