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Biomedical subjects

A M Udén

Publications and source records attributed to A M Udén.

At least 19 recordsLinked to original sources
PubMed1996

Intensive treatment in order to minimize the Ph-positive clone in CML. Danish-Swedish CML Group.

With the rationale that a significant reduction of the malignant clone in CML might prolong time to metamorphosis, intensive treatment was given to patients < or = 55 years. Six months of hydroxyurea and high dose interferon-alpha (IFN-alpha) was followed by one to three courses of intensive chemotherapy. Patients who had a donor were allotransplanted and patients who became Ph-negative in bone marrow were autotransplanted. On 1 May 1995, 160 patients were registered in the study. Fifty-one percent of the patients who received six months IFN-alpha and hydroxyurea had a significant Ph-reduction and 5% became Ph-negative. The corresponding figures after two intensive chemotherapy courses were 47 and 28%, respectively. Twenty-seven of 30 autotransplanted patients have been analysed for Ph. Seventeen have relapsed cytogenetically, while ten are Ph-negative 1-64 + months after ABMT. BMT was performed in 59 patients. The actuarial 6-year survival from diagnosis of all 160 registered patients is 68%, which seems to be better than for age-matched historical controls.

Adolescent↗
PubMed1993

Intensive treatment in order to minimize the Ph-positive clone in chronic myelogenic leukemia.

Several studies indicate that interferon (IFN) treatment, intensive chemotherapy and autologous bone marrow transplantation (ABMT) effectively reduce the Ph-positive clone in Chronic Myelogenic Leukemia (CML). In the present study on patients < or = 55 years, we have combined these three treatment modalities. The aim of the study was to eliminate or minimize the Ph-positive clone to see whether a status of minimal residual or Ph-negative disease could be maintained for a longer period of time. After diagnosis, patients received interferon (IFN-a-2b) and hydroxyurea (HU) to keep the white blood cell (WBC) and platelet count below 2-4 and 100-150 x 10(9)/l, respectively. After six months of treatment, Ph-analysis was performed. Patients with Ph-positive cells in bone marrow then received 1-3 courses of intensive chemotherapy. In patients Ph-negative after two courses, bone marrow was harvested and used for ABMT. After a third course, patients with up to 50% Ph-positive metaphases were accepted for ABMT. As of January 1, 1993, 97 patients were registered in the study. Six months of IFN+HU reduced the percentage of Ph-positive metaphases in 57% of the patients (7% became Ph-negative). The corresponding figures after two intensive cytotherapies were 70% (40% Ph-negative). Eighteen patients were autotransplanted. Seven have relapsed with Ph-positivity 3-22 months after ABMT, while nine are Ph-negative at 1-32+ months after ABMT (two not yet analyzed). Seventeen patients are alive and well, while one died one month after ABMT due to interstitial pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Successful treatment of hepatosplenic candidiasis with a liposomal amphotericin B preparation.

The case of a granulocytopenic patient with acute undifferentiated leukaemia and hepatosplenic candidiasis who was refractory to conventional deoxycholate amphotericin B (AmpB) and 5-flucytosine therapy is reported. He experienced severe AmpB-related side-effects, and was subsequently successfully treated with a pharmaceutical preparation of AmpB (5.7 g) entrapped in sonicated liposomes, composed of lecithin, cholesterol and stearylamine in a molar ratio of 4:3:1. Three months later, during maintenance chemotherapy, liposomal AmpB (5.1 g) was reinstituted due to the finding of biopsies positive for Candida albicans at bronchoscopy. After healing of the patient's fungal infection a left upper lobe resection was performed, which showed advanced fibrosis with signs of inflammation, but no evidence of fungal disease. Since no acute side-effects and only moderate hypokalaemia were observed, it appears that liposomal AmpB is superior to conventional AmpB treatment in granulocytopenic patients with hepatosplenic candidiasis and unbearable therapy-related side-effects.

Acute Disease↗
PubMed1991

Storage of platelets in a new plastic container. Polyvinyl chloride plasticized with butyryl-n-trihexyl citrate.

The effect of storage of platelets in a new polyvinyl chloride (PVC) plastic material with a butyryl-n-trihexyl citrate (BTHC) plasticizer (PL 2209) was evaluated. The PL 1240 container, i.e. PVC plastic with a different plasticizer, tri-(ethylhexyl)-tri-mellitate, was used as a reference. Measurements of pH, pO2, pCO2, glucose, lactate, adenosine triphosphate, total adenine nucleotide content, lactate dehydrogenase and platelet factor 4 (PF4) were made during 5 days of storage. Similar results were noted comparing PL 2209 and PL 1240. Differences in pO2 and pCO2 indicate greater gas permeability in PL 2209 than in PL 1240. Significantly higher PF4 levels were found in PL 2209, but the difference could not be attributed to the PL 2209 container itself. Paired autologous reinfusion studies (111Indium) of 6 normal donors gave mean recovery values after 5-day storage of 41.1 +/- 7.4% (PL 2209) and 45.5 +/- 7.7% (PL 1240), t1/2 66 +/- 13 and 75 +/- 5 h, survival time (linear model) 6.3 +/- 1.0 and 6.8 +/- 0.7 and survival time (multiple-hit model) 6.0 +/- 0.7 and 6.5 +/- 0.4 days, respectively. Only the difference in survival time (multiple-hit) was significantly higher in PL 1240. The corrected count increments at 12-24 h following transfusion were 13,300 +/- 10,800 (PL 2209) and 13,600 +/- 11,600 (PL 1240) with no statistically significant difference found. These results indicate PL 2209 as an equivalent alternative to PL 1240 for the 5-day storage of platelets.

Blood Component Transfusion↗
PubMed1988

Therapeutic effects of low-dose cytosine arabinoside, alpha-interferon, 1 alpha-hydroxyvitamin D3 and retinoic acid in acute leukemia and myelodysplastic syndromes.

62 evaluable patients with myelodysplastic syndromes (MDS) or acute leukemia were treated with different combinations of low dose ara-C, alpha-interferon (IFN), 1 alpha-hydroxyvitamin D3 (vit D3) and retinoic acid. The aim was to study the efficacy and toxicity of each combination. The overall rate was 44%. Of these, 50% responded favorably to the combination of IFN, vit D3 and retinoic acid (IDR), which was comparable to the response rate of 43% for low-dose ara-C. The results of the IDR treatment may be explained by additive or synergistic effects between the separate drugs in the combination. Ara-C and IDR treatment was generally well-tolerated but interferon gave more side effects than any other drug used in the study. Evaluation of the full combination of ara-C, IFN, vit D3 and retinoic acid was not possible because of toxicity. Marrow hypoplasia was infrequent (5/27 patients) in cases responding favorably to treatment. Complete remissions were not longer than partial remissions or significant responses.

Actuarial Analysis↗
PubMed1986

Relation to chemotactic factor gradients to neutrophil migration and orientation under agarose.

Chemotactic substances confer a migratory pattern for neutrophil granulocytes under agarose that is characteristic for each agent. To analyse the cause of such differences, we have studied neutrophil migration and orientation with f-Met-Leu-Phe (fMLP), leukotriene B4 (LTB4), and serum as chemoattractants. When these agents were used at optimal concentrations, it was observed that cells stimulated by LTB4 did not start migration as fast and did not migrate as far as those exposed to fMLP, but they maintained a higher degree of orientation. This delay in initiation of migration and maximal degree of orientation was even more marked when serum was the chemoattractant. These migration variables were related to the generation of gradients in the agarose of fML[3H]P, arachidonic-[3H]acid (AA, of which LTB4 is a metabolite), and fluorescein. The curvilinear AA gradient was flatter and more stable than those of fML[3H]P and fluorescein, which were linear. Thus, differences in the development and shape of the gradient of chemoattractant may contribute to differences in migration kinetics.

Cell Movement↗
PubMed1984

Effects of human interferon preparations on neutrophil function.

We have studied effects of two partially purified human leukocyte (alpha) interferon (IFN) preparations (PIF-A and PIF-B) and a highly purified fibroblast (beta) IFN on the functional activity of normal human neutrophils (PMNs). In vitro, PIF-B conferred a significant and dose-dependent enhancement of chemiluminescence (CL) induced both by phagocytosis and a soluble stimulus, f-Met-Leu-Phe, and decreased killing of Staph. aureus. In contrast, PIF-A caused only a slight inhibition of bactericidal activity and had no effects on CL. beta-IFN had no effects on either bactericidal activity or CL. Migration under agarose was decreased with all of the IFN but phagocytosis and release of enzymes was not affected. PMNs from seven patients treated with PIF-A for multiple myeloma exhibited increased CL responses but no other PMN functions were affected. The findings that human IFN preparations affect PMN functions indicate that high-dose IFN therapy of immunocompromised patients should be carefully evaluated for the possibility of increased infectious complications.

Bacteria↗
PubMed1983

Neutrophil functions and clinical performance after total fasting in patients with rheumatoid arthritis.

The effects of fasting for 7 days were investigated in 13 patients with rheumatoid arthritis (RA) in comparison with a control regimen in a cross-over trial. The effects of fasting on clinical performance and blood neutrophil functions were studied. During fasting, with a mean weight loss of 5.1 kg, clinical inflammation in the joints and the erythrocyte sedimentation rate (ESR) decreased. During the control period the joints either remained unchanged or deteriorated, and no change was observed in the body weight or the ESR. The locomotion of neutrophils under agarose, induced by a reference serum, decreased during the fasting period (p less than 0.001), but no change in their locomotion was induced by an Escherichia coli bacterial factor. During the control period, however, the locomotion induced by either stimulant was significantly decreased. Generation of migration-stimulating factors from the patients' plasma declined 3 days after the end of fasting (p less than 0.001). The adherence of the neutrophils to nylon fibres was unchanged during both periods. The bactericidal capacity improved during fasting, both in comparison with the initial value (p less than 0.005) and with the values from the control period (p less than 0.001). An association was found between improvement in inflammatory activity of the joints and enhancement of neutrophil bactericidal capacity. Fasting appears to improve the clinical status of patients with RA. This could partly be due to the observed changes in the functions of the neutrophils, since the latter contribute to the inflammatory joint reactions.

Adult↗
PubMed1983

Effects of novel lipoxygenase products on migration of eosinophils and neutrophils in vitro.

Since it has been suggested that a lipoxygenase product might be specific chemotactic factor for eosinophils, we assessed the stimulating effects of a variety of lipoxygenase products (LTB4, 20-OH-LTB4, 20-COOH-LTB4 and 5(S)12(S)-DHETE) on both neutrophil and eosinophil migration under agarose. LTB4 was the most potent lipoxygenase cytotaxin for neutrophils as well as eosinophils and its stimulating potential for both cell types was similar. The other leukotrienes stimulated migration of neutrophils less than LTB4, whereas eosinophils did not respond. Thus, the previous suggestion that an eosinophil chemotactic factor could be identical with LTB4 was not verified.

Cell Movement↗
PubMed1983

Leukotriene biosynthesis by polymorphonuclear leukocytes from two patients with chronic granulomatous disease.

Polymorphonuclear leukocytes (PMNL) isolated from two patients with chronic granulomatous disease (CGD) were tested for their ability to metabolize arachidonic acid to lipoxygenase products including 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4). Analyses of incubations of these PMNL with arachidonic acid and the calcium ionophore A23187 did not differ from simultaneous controls in the production of LTB4, other 5,12-dihydroxy-eicosatetraenoic acids, or monohydroxy-eicosatetraenoic acids. The clinical diagnosis of CGD was confirmed in both cases by determination of PMNL chemiluminescence. Leukocytes from both patients failed to generate active oxygen species in response to either LTB4 or formyl-methionyl-leucyl-phenylalanine. The observation of arachidonic acid oxidation in the absence of superoxide anion precludes a role for the active oxygen species in this metabolic process. These studies clearly dissociate the ionophore-induced leukocyte respiratory burst from the oxidation of arachidonate to the leukotrienes. In addition, the defect of CGD appears to be unrelated to the ability of PMNL to carry out arachidonate oxygenation.

Adult↗
PubMed1982

A novel leukotriene produced by stimulation of leukocytes with formylmethionylleucylphenylalanine.

Stimulation of human polymorphonuclear leukocytes with the chemotactic peptide formylmethionylleucylphenylalanine led to the formation of a novel leukotriene: 5(S),12(R)-dihydroxy-6,8,10,14-eicosatetraen-1,20-dioic acid. This dihydroxydicarboxylic acid is derived from omega-oxidation of 5(S),12(R),dihydroxy-6,8,10,14-eicosatetradienoic acid (leukotriene B4). The intermediate 5(S),12(R),20-trihydroxy-6,8,10,14-eicosatetraenoic acid was also isolated from these incubations. The two metabolites of leukotriene B4 exhibit chemotactic properties for human polymorphonuclear leukocytes but are less active in this respect than the parent compound.

Arachidonic Acids↗
PubMed1982

Neutrophil migration and orientation under agarose: findings in patients with the immotile cilia syndrome and effects of cytochalasin B and vinblastine.

This study has shown that the agarose technique is well suited for determination of whether impaired PMN migration is due to defective direction finding of deficient locomotive ability. By assessments of the degree of orientation of neutrophils together with measures of migration distances, we demonstrated that vinblastine treated normal neutrophils and PMNs from patients with the immotile cilia syndrome mainly move in a chemokinetic manner, whereas cytochalasin B hampers locomotive ability, but leaves direction finding intact. Hence, information whether chemotaxis or chemokinesis predominates is easily obtained in one single assay system.

Cell Movement↗
PubMed1982

Prednimustine and vincristine compared with cytosine arabinoside and thioguanine for treatment of elderly patients with acute nonlymphoblastic leukemia.

Sixty-seven patients with acute nonlymphoblastic leukemia (ANLL) and above the age of 60 years were randomly allocated to treatment with either prednimustine + vincristine or cycles with cytosine arabinoside and thioguanine. Of the 67 patients, 13 (19%) entered a complete remission and four a partial remission. Of 33 patients randomized to prednimustine and vincristine (15 adequately treated), three entered a complete remission and one a partial remission. Four further patients went into complete remission after a switch to other treatment modalities. Of 34 patients randomized to cycles of ARA-C and thioguanine (22 adequately treated), four entered a complete remission and three a partial remission with the correct program. One patient entered a remission with intermittent cytosine arabinoside + thioguanine (wrong program) and one further patient entered a complete remission after a switch to prednimustine and vincristine. Prednimustine + vincristine did not appear to be superior to treatment with cytosine arabinoside thioguanine cycles for elderly patients with ANLL.

Acute Disease↗