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Biomedical subjects

L O Hafström

Publications and source records attributed to L O Hafström.

At least 19 recordsLinked to original sources
PubMed2005

Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous vasopressin in non-resectable pancreas cancer.

BACKGROUND: Systemic palliative treatment with chemotherapy against advanced pancreas cancer has low effectiveness despite considerable toxicity. AIM: To investigate the safety, toxicity and tumour response of intraperitoneal 5-Fluorouracil (5-FU) with intravenous Leucovorin and to monitor 5-FU pharmacokinetics in plasma during intraperitoneal instillation with and without vasopressin in patients with non-resectable pancreas cancer. PATIENTS/METHODS: Between 1994 and 2003, 68 patients with non-resectable pancreas cancer TNM stage III and IV, were enrolled to receive intraperitoneal5-FU instillation 750-1500 mg/m2 and intravenous Leucovorin 100 mg/m2 for two days every third week. Tumour response, performance status and toxicity were recorded. Seventeen patients were also treated with intravenous vasopressin 0.1 IU/minute for 180 minutes, during intraperitoneal 5-FU instillation. Area under the curve (AUC) and peak concentration (Cmax) of 5-FU in plasma were analysed. RESULTS: The treatment was well tolerated with minor toxicity. One complete response (54.1+ months) and 2 partial responses were observed. Time to progression was 4.4 months (0.8-54.1+), and median survival was 8.0 months (0.8-54.1+). There was a significant reduction of 5-FU Cmax in plasma the second day of treatment if vasopressin was used (3.4+/-2.5 and 6.1+/-5.4 mumol/l, respectively, p<0.05). 5-FU AUC in plasma was not significantly affected by vasopressin either day of treatment. CONCLUSION: Intraperitoneal 5-FU is a safe treatment with low toxicity to patients with non-resectable pancreas cancer. Tumour response was 4.4% and median survival time 8.0 months. Addition of vasopressin did not significantly decrease plasma 5-FU AUC but reduced Cmax on day 2 of treatment.

Adenocarcinoma↗
PubMed2004

Effect of carcinomatosis and intraperitoneal 5-fluorouracil on peritoneal blood flow modulated by vasopressin in the rat as measured with the 133Xe-clearance technique.

PURPOSE: Intraperitoneal administration of 5-fluorouracil for the treatment of gastrointestinal malignancies results in a greater total drug exposure in the peritoneal fluid than in plasma. Drugs are eliminated from the peritoneal cavity mainly by capillaries leading to the portal venous system and to a lesser extent by lymphatics. The drug itself and the presence of peritoneal carcinomatosis may affect elimination of the drug. The 133Xe-clearance technique allows the influence of a vasoactive agent on the peritoneal blood flow to be estimated with minimal invasiveness. The aim of the present study was to explore whether intraperitoneal 5-FU or peritoneal carcinomatosis affects the peritoneal blood flow and its reactivity to intravenous vasopressin, as measured indirectly with the 133Xe-clearance technique. METHODS: The animals used in this study were 63 Wistar-Fu (W-Fu) rats and 67 Lister-Hooded (LH) rats. On day 0, either 5-FU at 25 mg/kg body weight in 25 ml/kg isotonic saline was instilled intraperitoneally, or 1 x 10(5) syngeneic tumour cells were inoculated intraperitoneally. On days 1, 2 and 3 in the 5-FU-treated rats, and on days 12-16 in rats inoculated with tumour cells, peritoneal blood flow was analysed with the 133Xe-clearance technique, before and during intravenous infusion of vasopressin at 0.07 IU/min/kg body weight. RESULTS: The basal 133Xe-clearance before administration of vasopressin was similar in all groups except in the LH rats treated with 5-FU in which it was significantly lower. Infusion of vasopressin induced a significant decrease in 133Xe-clearance of the same magnitude in controls and in tumour-bearing rats. In the rats given intraperitoneal 5-FU, vasopressin did not reduce the 133Xe-clearance the first day after administration of 5-FU. CONCLUSIONS: Intravenous vasopressin at 0.07 IU/min/kg decreased peritoneal blood flow as measured indirectly with the 133Xe-clearance method. Intraperitoneal 5-FU abrogated the reduction in peritoneal blood flow with intravenous vasopressin the first day after treatment. In contrast, the presence of peritoneal carcinomatosis did not influence peritoneal blood flow, nor the effect of vasopressin

Animals↗
PubMed2001

Treatment of non-resectable pancreatic cancer with intraperitoneal 5-FU and leucovorin IV.

AIM: To explore the feasibility of intraperitoneal (IP) 5-fluorouracil (5-FU) and (IV) leucovorin for patients with advanced pancreatic carcinoma. MATERIALS AND METHOD: Thirty patients (11 men), median age 65 (range 36-74 years), with a non-resectable pancreatic carcinoma in stage III (n=2) and IV (n=28) were treated with IP 5-FU 750-1000 mg/m(2)and leucovorin IV 100 mg/m(2)for 2 days every 3rd week. Tumour effect was analysed with repeated computed tomography (CT) scans, performance status was estimated with Karnofsky's index (KI) and morphine consumption, and toxicity assessed using World Health Organization (WHO) criteria. RESULTS: Median survival time was 7 months (range 0-21). There was no difference in survival between patients with different grading, staging or tumour size. Regional and systemic toxicity: The treatment was well tolerated, with no grade III or IV complications or side-effects. The median KI showed a minor reduction during treatment. The median morphine consumption per 24 hours increased from 0 mg (range 0-250) at inclusion, to 70 mg (range 0-540) at exclusion. The median nadir (WBC) was 7.2x10(3)/mm(3)(range 5.2-18.8). All patients had abdominal discomfort and distension during IP installation. CONCLUSION: Intraperitoneal administration of 5-FU is feasible for patients with nonresectable pancreatic carcinoma. The treatment can induce a temporary stabilization of tumour growth and eventually prolong survival without adverse effects.

Adult↗
PubMed1997

The Gothenburg breast screening trial: first results on mortality, incidence, and mode of detection for women ages 39-49 years at randomization.

BACKGROUND: The effect of mammography screening on breast carcinoma mortality in women ages < 50 years remains unclear. METHODS: A randomized trial of invitation to breast carcinoma screening with mammography was performed in the city of Gothenburg, Sweden. The purpose was to estimate the effect of mammographic screening on breast carcinoma mortality in women ages < 50 years. Randomization was initially by day-of-birth cluster (18% of subjects), and subsequently by individual (82% of subjects). Between September 1983 and April 1984, 11,724 women ages 39-49 years were randomized to the study group. This group was invited to mammographic screening every 18 months. Two-view mammography was used at each screen unless the density of the breast at the previous screen indicated that single view was adequate. Fourteen thousand two hundred and seventeen women in the same age range were randomized to a control group that was not invited to undergo screening until the fifth screen of the study group (between 6 and 7 years after randomization). Women with breast carcinoma diagnosed up to the time immediately after the first screen of the control group were followed for death from breast carcinoma until the end of December 1994. RESULTS: A 45% reduction in mortality from breast carcinoma was observed in the study group compared with the control group (relative risk [RR] = 0.55, P = 0.035, 95% confidence interval [CI], 0.31-0.96). A conservative estimate based on removal of the tumors detected at the first screen of the control group gave a mortality reduction of 44% (RR = 0.56, P = 0.046, 95% CI, 0.31-0.99). In both cases, the effect was statistically significant. CONCLUSIONS: Mammographic screening can reduce mortality from breast carcinoma in women ages < 50 years. The mortality reduction can be substantial if high quality mammography is used and an 18-month interscreening interval is strictly adhered to.

Adult↗
PubMed1995

Antitumour effects of pure diastereoisomers of 5-formyltetrahydrofolate in hepatic transplants of a rodent colon carcinoma model.

The effects of the two diastereoisomers of 5-formyltetrahydrofolate on tumour growth, thymidylate synthase (TS, EC 2.1.1.45) levels, and potentiation of 5-fluorouracil cytotoxicity were studied in an in vivo rat colon carcinoma model, transplanted to liver. The animals were randomized into eight groups, treated with daily i.v. tail vein injections of racemic (d,l)-5-formyltetrahydrofolate (5-CHO-FH4), 15 mg/kg, (1)-5-CHO-FH4 7.5 mg/kg, and (d)-5-CHO-FH4 7.5 mg/kg, 5-fluorouracil (FUra) 30 mg/kg, (d,l)-5-CHO-FH4 15 mg/kg+FUra 30 mg/kg, (l) 5-CHO-FH4 7.5 mg/kg+FUra 30 mg/kg, and (d)-5-CHO-FH4 7.5 mg/kg+FUra 30 mg/kg, and a sham-treated control group. The average tumour size of the groups was equal at the start of treatment. After six days' treatment the average tumour sizes were at laparotomy 3.3 +/- 1.0 g in the (d/l)-5-CHO-FH4 treated group, compared to 2.0 +/- 0.1 g in the FUra treated group and 7.1 +/- 3.1 g in the controls. Natural (l)-5-CHO-FH4 promoted tumour growth (average tumour weight 10.8 +/- 4.0 g), whereas the unnatural (d)-5-CHO-FH4 alone retarded it (average tumour weight 1.2 +/- 0.40 g). (l)-5-CHO-FH4 induced a significant increase in tumour tissue TS levels by [3H]FdUMP radioligand assay (27.5 +/- 8.4 pmol/g tumour tissue) compared to controls (16.8 +/- 6.1 pmol/g tumour tissue). Increases in 5,10-methylenetetrahydrofolate and tetrahydrofolate occurred with FUra alone, with a further statistically significant increase in both folates with the addition of (d)-5-CHO-FH4 to FUra.

Animals↗
PubMed1993

Plasma nitrate as an index of immune system activation in animals and man.

The cytotoxic activity of activated macrophages is based upon their formation and release of nitric oxide (NO). In blood NO is rapidly metabolised to nitrate. We analysed plasma nitrate in rats given zymosan, an activator of the immune system, and found 20-fold increases above the basal level. Furthermore, in two human subjects with acute gastro-enteritis plasma nitrate increased from about 30 to 200 microM two days after onset of symptoms. These increased plasma levels of nitrate may reflect macrophage formation of NO. We propose that plasma nitrate may be a useful index for quantitative assessment of cytotoxic activity during immunological challenge.

Acute Disease↗
PubMed1991

Comparison of seven iodine-labelled monoclonal antibodies in nude mice with human colon carcinoma xenografts.

The biokinetics of seven 131I-labelled monoclonal antibodies (MAbs), directed against human colon carcinoma and one 125I-labelled unspecific MAb have been examined. The study in nude mice, carrying human colon carcinoma, was intended to be a step in the selection of the most suitable antibody for clinical scintigraphy. The biological half-life in blood was found to be between 1.3 and 7.4 days for the different MAbs. Chromatography of plasma samples showed that the radioiodine was mainly bound to IgG-sized molecules. The (normal tissue)/blood ratios were similar for all the MAbs. The tumour/blood ratio was 0.41 for the unspecific MAb and 0.49-1.1 for the specific MAbs, and the tumour/muscle ratio was between 3.2 and 6.8 for the specific MAbs 6 days after injection. For one MAb tumour/blood and tumour/muscle ratios were 3.9 and 9.8 respectively 9 days after injection. Localization indices were at their highest 2.6 6 days after injection. For at least two of the monoclonal antibodies the tumour/blood and tumour/muscle ratios found are high enough to justify clinical trials regarding their usefulness for scintigraphy of colon cancer in man.

Adenocarcinoma↗
PubMed1989

Pharmacokinetics of intra-arterial mitomycin C with or without degradable starch microspheres (DSM) in the treatment of non-resectable liver cancer.

The effects of degradable starch microspheres (DSM) on mitomycin C pharmacokinetics and bone marrow toxicity were studied in a phase II multicenter study. Sixty-three patients with non-resectable primary or secondary liver cancer were randomized to receive either i.a. mitomycin C 15 mg/m2 first, followed 5 weeks later by mitomycin C 15 mg/m2 plus DSM 360 mg administered into the hepatic artery (group I) or the same treatments in the opposite sequence (group II). In 36 out of 47 patients who received at least 2 treatments, peripheral venous blood samples were analyzed for mitomycin C pharmacokinetics on a minimum of 2 paired courses. In all patients, the area under the concentration time curve (AUC) was significantly lower when the drug was co-administrated with DSM, but the terminal half-life (t1/2) of mitomycin C was unchanged. In group I the addition of DSM resulted in a significantly lowered AUC, but not in group II. The discrepancy between the 2 groups is probably due to differences in DSM-induced intra-hepatic shunting. The addition of DSM resulted in significantly higher platelet nadir values, but unchanged white blood cell count nadir value. In conclusion, DSM reduce the systemic exposure of mitomycin C and seem to lessen the haematologic toxicity judged from a less pronounced decrease in platelets.

Adult↗
PubMed1986

Metabolism of mammary, abdominal, and femoral adipocytes in women before and after menopause.

In 23 women before and 11 after menopause, adipocyte size, lipoprotein lipase activity, and lipolytic responsiveness to norepinephrine were compared in different regions of adipose tissue. In premenopausal women femoral adipocytes were characterized by a higher lipoprotein lipase activity than abdominal or mammary adipocytes. On the other hand, lipolytic responsiveness and sensitivity in the latter two was higher than in femoral tissue. In postmenopausal women no differences in lipoprotein lipase or lipolysis were found among the three regions. Consequently, menopause in women seemed to be associated with a diminution of not only the increased lipoprotein lipase activity of femoral adipocytes, but also of the high lipolytic response in abdominal and mammary adipose tissue. It is therefore suggested that female sex steroid hormones exert regionally specific effects, ie, increasing lipoprotein lipase in femoral adipocytes, which therefore become enlarged. It also seems possible that stimulation of lipolysis in abdominal and mammary adipocytes is an effect of sex steroid hormones. From the results obtained it is hypothesized that the secondary sex characteristics of adipose tissue distribution in women might be caused by regionally specific effects of sex steroid hormones on adipocyte metabolism.

Abdomen↗
PubMed1980

Retroperitoneal sarcoma: ultrasonographic and angiographic evaluation.

Fifteen patients with retroperitoneal sarcoma were examined by angiography. Preoperative abdominal ultrasonography was performed in nine of them. Ultrasonography demonstrated in all nine cases a solid mass with characteristic echo-pattern with an echo-rich central area and an echo-poor periphery. Angiography demonstrated an avascular mass in one case, a hypovascular in four, and a hypervascular in ten cases. The techniques of both methods are discussed. The value of ultrasonography as a diagnostic procedure at the time of initial evaluation and angiography as an important diagnostic tool for localization of the mass and for achievement of anatomical details important for surgery is stressed.

Adult↗
PubMed1978

Treatment of liver cancer with regional intraarterial 5-FU infusion.

The results of a retrospective three year study of forty-six patients with cancer of the liver treated with regional intraarterial infusion of 5-FU are reported. No primary mortality was noted. Oblective overall remission rate was 43 per cent. Overall median survival from onset of treatment was six months. The one year survival rate was 33 per cent and the two year survival rate 11 per cent. Patients with an objective response had a significantly prolonged survival as compared with nonresponders, especially in the colorectal group: sixteen months versus four months. Survival was not related to tumor size and involvement of the liver. During treatment 42 per cent of the patients developed extrahepatic metastases. Quality of life was improved in 63 per cent of the patients. The results indicate that infusion therapy induces reasonable response and palliation but is inadequate for the control of extrahepatic tumor growth.

Adult↗
PubMed1976

Inactivation of 5-fluorouracil by the liver during continuous regional and systemic infusion in pigs.

During continuous systemic or portal infusion of 5-fluorouracil (5-FU) to anaesthetized pigs, the cytostatic activity was reduced in blood traversing the liver. The liver eliminated between 15 and 50% of the amount 5-FU given per time unit. During jugular infusion the concentration of cytostatic compounds in portal blood was equal to or less than in systemic blood. The cytostatic activity was much higher in portal blood and lower in systemic blood during portal infusion. The findings speak in favour of portal infusions of 5-FU to patients with disseminated cancer in the liver.

Animals↗