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Biomedical subjects

L Domellöf

Publications and source records attributed to L Domellöf.

At least 37 records · Page 2Linked to original sources

Therapeutic concentrations of melphalan do not affect yeast cell phagocytosis by monocytes.

The effect of melphalan on monocyte phagocytosis was assessed by studying the uptake of fluorescent yeast cells by glass-adherent monocytes (a fluorescence-quenching technique). In contrast to several other cytotoxic agents, melphalan did not inhibit monocyte phagocytosis. Although the main immunosuppressive side effect of most cytotoxic drugs appears to be due to bone marrow depression with reduction of leukocyte counts, it is reasonable to assume that lack of interference with the function of mature leukocytes is a favourable feature of an antineoplastic drug.

Humans↗

The effects of omeprazole and cimetidine on duodenal ulcer healing and the relief of symptoms.

In a Swedish double-blind multicentre study, omeprazole (30 mg o.m.) was compared with the H2-receptor antagonist cimetidine (400 mg b.d.) in 152 patients. Clinical assessments and laboratory investigations were carried out at 2 and 4 weeks, and again at 6 weeks in unhealed patients. Endoscopy was performed at 2 weeks, and again at 4 and 6 weeks in unhealed patients. The patients in the two groups were well-matched prior to treatment. Omeprazole was superior to cimetidine in ulcer-healing rate after 2, 4 and 6 weeks. After 2 weeks of treatment, 66% of the omeprazole- and 45% of the cimetidine-treated patients were healed (P = 0.02), after 4 weeks 97 and 84% (P = 0.01), and after 6 weeks 100 and 92% (P = 0.02), respectively. There was a more pronounced improvement in the patients' symptoms in the omeprazole group after 2 weeks (P = 0.05). Both drugs were well-tolerated, but there was a high prevalence of patients with adverse events in the cimetidine group (51%, compared to 30% of the omeprazole group; P = 0.02). A total of 125 patients were followed for 6 months after healing. The patients were investigated by endoscopy after 6 months, or whenever symptoms occurred. There was no significant difference in the rate of relapse within 6 months between the two treatment groups: 54% relapsed in the omeprazole group and 52% in the cimetidine group. In conclusion, 30 mg of omeprazole, given once daily, is superior to 400 mg of cimetidine twice daily in duodenal ulcer healing; but ulcer relapse in the two groups appears to be equivalent.

Adolescent↗

Splenic release of amino acids in man assessed by arterial and venous blood sampling in situ.

The splenic arteriovenous differences in plasma amino acid concentrations were assessed in situ by peroperative sampling in 11 patients undergoing splenectomy because of benign and malignant hematologic diseases. The total difference was about 250 mumol/l, which suggests that the spleen contributes about 11 mumol/100 g spleen/min of amino acids to the portal vein. This means that the liver extraction of amino acids may be at least 10% greater than previously believed.

Amino Acids↗

Role of actin polymerization in monocyte phagocytosis of yeast cells effect of cytochalasin B.

The role of the cortical actomyosin-like contractile system in monocyte phagocytosis was studied by means of inhibition with cytochalasin B. Monocyte phagocytosis of yeast cells was assayed with a fluorescence extinction technique of surface-located phagocytosis which distinguishes between adherence and ingestion phases of total phagocytosis. Cytochalasin B, 10 micrograms/ml, inhibited monocyte phagocytosis by 20-30%. The cytochalasin inhibition was significant and restricted to the ingestion phase. The finding supported the hypothesis that the contractile structures of the cell have a contributory role in IgG-mediated monocyte phagocytosis on a surface. It is suggested that the cytochalasin effect reflected the role of chemotaxis in monocyte phagocytosis assayed by the present technique.

Actins↗

Distribution and metabolism of N'-nitrosonornicotine in the miniature pig.

The distribution and metabolism of [5-3H]N'-nitrosonornicotine ([5-3H]NNN) was studied in three 18-day-old miniature pigs. [5-3H]NNN was administered by intracardiac administration into the right ventricle of the heart to mimic uptake by the lung. Whole body autoradiograms taken 15-220 min after treatment showed high levels of radioactivity in the mandibular and parotid salivary glands, Harder's gland, lacrimal glands, glands of the snout and respiratory part of the nasal cavity, and the melanin of the eyes and skin. Bound radioactivity was most abundant in the nasal mucosa and liver. Analysis of tissues by h.p.l.c. showed the presence of high levels of [5-3H]NNN in the mandibular glands and Harder's gland. Levels of [5-3H]NNN and its metabolites were determined in arterial and venous serum, 0.5-220 min after injection. The disappearance of [5-3H]NNN from serum was biphasic. 4-Oxo-4-(3-pyridyl) butyric acid, a metabolite of [5-3H]NNN resulting from 2'-hydroxylation, which is a suspected activation pathway, was detected 0.5 min after injection and appeared to reach a steady state 2-220 min after injection. 4-Hydroxy-4-(3-pyridyl)butyric acid, from 5'-hydroxylation of [5-3H]NNN, and norcotinine, from denitrosation, were also rapidly formed. These experiments are the first in which the appearance of NNN metabolites in blood has been measured. The ratio of 2'-hydroxylation to 5'-hydroxylation varied from 0.27 to 0.60 in arterial serum and from 0.33 to 0.49 in venous serum in the period from 2-220 min. [5-3H]NNN accumulated in the stomach contents such that its levels were greater than those in arterial or venous serum, 60 min after injection. The results of this study demonstrate that the miniature pig is a useful model for the investigation of nitrosamine metabolism and indicate some similarities and differences in metabolism and distribution compared with the rat.

Animals↗

Effects of fluorouracil, doxorubicin and FAM combination on human peritoneal macrophages.

The effects of fluorouracil and adriamycin as single drugs and in combination with mitomycin (FAM) on the phagocytosis of tissue macrophages were studied in vitro. Human peritoneal macrophages (HPM) from cancer patients or uremic patients on peritoneal dialysis were incubated with the test drugs. No apparent inhibition of the adherence, engulfment or total phagocytosis of yeast cells was found with the fluorescence quenching technique. This is in contrast to our previous findings on blood monocytes. Thus the heterogeneity in sensitivity to anticancer drugs is probably related to cell maturity and cell surface characteristics.

Adolescent↗

Therapeutic concentrations of griseofulvin do not affect yeast cell phagocytosis by monocytes.

The effect of griseofulvin on monocyte phagocytosis was assessed by studying the uptake of fluorescent yeast cells by glass-adherent monocytes (a fluorescence-quenching technique). In contrast to other microtubule antagonists, griseofulvin did not inhibit monocyte phagocytosis. It is suggested that the lack of griseofulvin interference with essential leukocyte functions is a possible explanation for the fact that the microtubule antagonist griseofulvin serves as a comparatively safe and harmless drug.

Adhesiveness↗

Cardio-pulmonary elimination of 5-fluorouracil after bolus injection in the hepatic artery.

Theoretically, administration of 5-fluorouracil (5-FU) into the hepatic artery should improve the clinical response rate by high tumor cell extraction of the drug. However, previous studies in animals and man have also found a major extrahepatic elimination route for 5-FU. In the present study of 7 patients with primary and secondary liver cancer, we have found indications that a considerable elimination of 5-FU takes place in the cardio-pulmonary circuit. Thus, the mean AUC in the hepatic vein was 7185 mumol X min X l-1 and 3792 in a peripheral vein.

Adult↗

Gastrointestinal manifestations of hereditary haemorrhagic teleangiectasia.

Six out of 34 patients with gastrointestinal manifestations of hereditary haemorrhagic teleangiectasis (HHT) were found retrospectively. The diagnosis was established clinically, endoscopically, angiographically and/or at surgery. Major bleeding episodes originated from lesions in the stomach and duodenum. A few cases were also encountered with teleangiectasia in the small and large intestine and occasionally in the liver and lung. Repeated treatment with electrocoagulation was effective in controlling gastrointestinal bleeding in two of the patients. It is concluded that HHT should be considered as a potential cause of repeated and unexplained GI bleedings and that this diagnosis also should be kept in mind in patients with recurrent epistaxis.

Epistaxis↗

Effects of partial hepatectomy on plasma fibronectin concentrations in the rat.

Rats were subjected to 60% partial hepatectomy. In the immediate postoperative period, there was a small decline in plasma fibronectin concentrations, which was normalized already 12 h post-operatively. Metabolic labelling of fibronectin with 35S-methionine showed that the rate of incorporation of label was unchanged after partial hepatectomy. However, when the abdominal viscera were excluded from the circulation, no incorporation of label was found. These results show that the rate of fibronectin biosynthesis has the rapid regulation characteristics of an acute phase reactant. Peripheral tissues do not contribute significantly to the plasma fibronectin concentration. Intra- or retro-peritoneal viscera, most likely the liver, are responsible for the synthesis of rat plasma fibronectin.

Animals↗

Response of human monocyte phagocytosis to FAM (fluorouracil, adriamycin, mitomycin).

The immunosuppressive effect of chemotherapy associated with surgery is poorly understood. The effect of combination chemotherapy--fluorouracil, adriamycin and mitomycin (FAM)--on monocyte phagocytosis was tested in patients operated on for gastric cancer. The adherence, engulfment and total phagocytic process were studied with a fluorescence-quenching technique 1 hour, 24 hours and 1 week after 19 FAM treatments in nine patients. The engulfment of yeast cells and the total phagocytosis were significantly impaired 1 hour post-treatment (p less than 0.05 and less than 0.01, respectively). These functions had normalized after 24 hours, but after 1 week the engulfment step was significantly depressed (p less than 0.05). Significantly increased adherence of yeast cells (p less than 0.05) was found at the same time. The initial, transient depression of monocyte phagocytosis probably was related to inactivation of cell-surface receptors. The late (1 week) depression probably was due to bone-marrow toxicity. This functional impairment of the blood monocytes was not reflected as clinical liability to infections.

Aged↗

Phagocytosis of yeast cells by monocytes: effects of fluorouracil, doxorubicin and mitomycin.

The drugs in the FAM combination (fluorouracil, doxorubicin, mitomycin) were tested for a possible effect on monocyte function by means of a glass-surface fluorescence-quenching technique of monocyte phagocytosis. The individual drugs significantly inhibited monocyte phagocytosis. The inhibition was located at the engulfment phase of phagocytosis and in an order of magnitude of 20-30%. The FAM combination did not suppress monocyte phagocytosis more than each one of the individual drugs. It is suggested that a slight inhibition of monocyte phagocytosis is a cost of cytotoxic treatment.

Cell Adhesion↗

A pharmacokinetic study of adriamycin and 4'epi-adriamycin after simultaneous intra-arterial liver administration.

The plasma pharmacokinetics of adriamycin and 4'epi-adriamycin were studied in patients with malignant tumors of the liver after simultaneous regional administration of equal amounts of the two anthracyclines by the arterial route. The use of a highly selective liquid chromatographic analytical method permitted quantification of plasma concentrations of the two drugs as well as their corresponding 13-hydroxy metabolites. The plasma concentrations of each drug followed a three-compartment open model. On average the area under the plasma concentration time curve (AUC) and the maximum plasma concentration (Cmax) were 2.1 and 1.7 times larger for adriamycin than for 4'epi-adriamycin, respectively. 4'Epi-adriamycin was eliminated faster than adriamycin, the terminal half-life time being on the average 1.5 times higher for adriamycin. These findings are in agreement with what has previously been observed after intravenous administration. The plasma concentrations of the 13-hydroxy metabolites did not exceed 30 ng ml-1. The AUC values of these metabolites were on average 20% of the AUC values of the intact drugs.

Adult↗

Effects of CCNU on monocyte phagocytosis.

The effect of CCNU on human monocyte phagocytosis of yeast cells was measured in vitro. 'Therapeutic' CCNU concentrations had no measurable effect on monocyte phagocytosis. Higher concentrations of CCNU had a slight but statistically significant effect on the engulfment phase of monocyte phagocytosis. The results suggest that CCNU treatment is of minor importance for monocyte function.

Cells, Cultured↗

The phagocytic process of human peritoneal macrophages in cancer or uremia.

The ingestion and adherence components of the overall phagocytic process have been studied in human peritoneal macrophages (HPM) from cancer or uremic patients and compared with HPM from healthy controls. No difference was found in the studied functions between cancer patients and controls. However, HPM from uremic patients showed a highly significant impairment in the overall phagocytosis and the studied components of this function. In all groups the ingestion phase was significantly depressed after 24 hours of culture. Despite this functional impairment, the total phagocytic process was unchanged, owing to a significant increase in the adherence of test particles.

Adolescent↗