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Biomedical subjects

G Oberg

Publications and source records attributed to G Oberg.

At least 73 records · Page 4Linked to original sources
PubMed1988

Inter- and intraindividual differences in oral chlorambucil pharmacokinetics.

Inter- and intraindividual variation in the pharmacokinetics of oral chlorambucil was investigated in patients with chronic lymphocytic leukaemia. Five patients were given in randomized order 15, 40, 60 and 70 mg chlorambucil p.o. and plasma was analyzed for chlorambucil and its cytotoxic metabolite phenyl acetic acid mustard. The area under the plasma concentration-time curve of chlorambucil varied two- to fourfold between patients at each dose level. The AUC of the metabolite was higher and showed twofold interindividual variation. The intraindividual dose-corrected AUCcs also varied twofold. No dose dependency of the dose corrected AUC was seen either for chlorambucil or the metabolite. Elimination of both compounds form plasma was rapid, with half-lives of 1.01 and 1.94, respectively.

Administration, Oral↗
PubMed1988

Chronic B-lymphocytic leukemia--expression of B cell activation markers in relation to activity of the disease.

Two-color FACS analysis was used to study phenotypic subset and activation markers on circulating B (tumor) cells of 21 patients with chronic B-lymphocytic leukemia (B-CLL). Patients with clinically active (progressive) disease differed from patients with stable disease: B cells from the former patient category showed a significantly increased expression of the activation antigen 1D11 and FN99(CD9), and a decreased expression of the FN1 B subset marker. No clinical associations were observed using the CD23, CD25, 4F2, Ba, Bac-1 or FN50 markers. Functional studies showed that the B cells from both clinical categories of patients responded equally well with DNA synthesis when optimally triggered and supplied with T cell factors. However, B-CLL cells from patients with progressive disease secreted significantly higher levels of IgM in response to phorbol ester. The present experiments thus show that differences exist in the activation of B-CLL cells in vivo and that these patterns are correlated with disease activity. Further, the maximal in vitro proliferative capacity of individual tumor cells is similar, whereas differences in accessory T cell functions may exist between patients.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1987

Beta 2-microglobulin, lysozyme and lactoferrin in cerebrospinal fluid in patients with lymphoma or leukaemia: relationship to CNS involvement and the effect of prophylactic intrathecal treatment with methotrexate.

Central nervous system (CNS) involvement in patients with leukaemia or lymphoma presents a diagnostic problem. This study was conducted to test whether combined measurements of various cellular markers such as beta 2-microglobulin (beta 2m), lactoferrin (LF) and lysozyme (LYS) in the cerebrospinal fluid (CSF) might aid in the diagnosis of CNS involvement in such patients. Forty-two patients were studied. Sixteen were considered to have CNS involvement and 26 showed no signs of such involvement. In the group with symptoms or signs of CNS involvement, nine patients out of 12 had increased total protein in CSF, 14 of 14 increased beta 2m, 14 of 16 increased LYS and five of 15 increased LF. In patients without CNS involvement total protein was increased in four of 25, beta 2m in three of 21, LYS in four of 28 and LF in one of 28 patients. The differences were statistically significant (P less than 0.01, P less than 0.001, P less than 0.001 and P less than 0.05, respectively). Prophylactic intrathecal methotrexate treatment in patients with acute lymphoblastic leukaemia caused an increase in the CSF of beta 2m, LYS and LF but not of total protein, which may reflect a drug-induced inflammatory reaction in the CNS. We conclude that combined measurements of the three cell markers add to our understanding of the cellular reaction to malignant cells in the CNS in leukaemia and lymphoma and may be valuable supplements in the diagnosis of this CNS involvement.

Adolescent↗
PubMed1987

Myeloid regeneration after bone-marrow transplantation monitored by serum measurements of myeloperoxidase, lysozyme and lactoferrin.

Bone-marrow regeneration after chemo- and radiotherapy-induced aplasia can be monitored by serum levels of myeloperoxidase (MPO), lysozyme (LYS) and lactoferrin (LF). In 10 patients with leukemia, serum measurements were performed before and after bone-marrow transplantation. Bone-marrow regeneration was suggested by increments in serum MPO and LYS 5 and 4 days prior to the increase in mononuclear cells (Mono) and 10 and 9 d before the increase in polymorphonuclear leukocytes (PMN) in the peripheral blood. LF started to rise 4.5 d before detectable circulating PMNs. 2 patients with early relapses of leukemia post transplantation are shown to display atypical patterns of serum MPO and LYS. We conclude that serum measurements of MPO, LYS and LF may be used as early and sensitive means to monitor bone-marrow activity during hematological regeneration. However, the findings also strongly support the earlier proposal that MPO alone may be used to reflect myeloid activity in the bone-marrow in general.

Adolescent↗
PubMed1987

Diagnostic and prognostic significance of serum measurements of lactoferrin, lysozyme and myeloperoxidase in acute myeloid leukemia (AML): recognition of a new variant, high-lactoferrin AML.

92 patients with acute myeloid leukemia were classified according to the FAB classification (M1 n = 20, M2 n = 43, M3 n = 1, M4 n = 19, M5a n = 2, M5b n = 2, and M6 n = 5 patients). Serum measurements of lactoferrin (LF), myeloperoxidase (MPO) and lysozyme (LYS) were performed before the start of treatment. LF was significantly lower in M1 when compared with M2 but not as compared to M4, MPO was significantly higher in M2 and M4 than in M1, but comparable MPO levels were found in M2 and M4. LYS was significantly elevated in M2 in comparison with M1, and in M4 when compared to both M1 and M2. Polymorphonuclear granulocytes (PMNs) in M1 were significantly reduced when compared with M2 and M4, whereas mononuclear cells were significantly increased in M4 in comparison with both M1 and M2. FAB classification did not generate any prognostic information. When the patients were, instead, subdivided according to LF levels were found prognostically significant differences. Of patients below 100 micrograms/l, 44% went into remission as compared to 77% with LF from 101 to 400 micrograms/l. In patients with LF levels above 400 micrograms/l the remission frequency was only 14%. Multivariate statistical analysis on the data further suggested that lactoferrin may be used as an independent prognostic indicator. We conclude that although determination of the serum-levels of lactoferrin, lysozyme and myeloperoxidase in certain cases may be valuable as a supplement to the morphological examination of acute myeloid leukemia, it is evident that none of the three determinations can be used alone to distinguish between the FAB groups.

Adult↗
PubMed1986

Bactericidal proteins and neutral proteases in diabetes neutrophils.

Reduced bacterial killing by polymorphonuclear leucocytes has been reported in patients with diabetes mellitus. Whether this is due to reduced content of bactericidal granular proteins has not been determined. We therefore immunochemically measured the content of myeloperoxidase, lactoferrin, lysozyme, cathepsin G and elastase in polymorphonuclear leucocytes from 50 insulin-treated diabetic patients. The peroxidase activity was also measured. Normal contents of myeloperoxidase and lactoferrin as well as normal peroxidase activity were found. The average contents of cathepsin G, elastase and lysozyme were 2.5, 3.2 and 2.6 micrograms/10(6) polymorphonuclear leucocytes, respectively, and thus 14, 45 and 18% higher than the contents of normal polymorphonuclear leucocytes. The results indicate that reduced intracellular killing of bacteria demonstrated in previous studies in diabetic patients does not appear to be related to a reduction in the content of bactericidal proteins.

Age Factors↗
PubMed1986

Bone-marrow regeneration after therapy-induced hypoplasia monitored by serum measurements of lactoferrin, lysozyme and myeloperoxidase.

Serum levels of lactoferrin, lysozyme and myeloperoxidase were measured sequentially after induction treatment in 30 patients with AML in order to test the hypothesis that these proteins may be used to monitor activity and different stages of myelopoiesis in the bone-marrow. The results showed that myeloperoxidase and lysozyme started to rise again 6-8 days after initiation of treatment as compared to 12 d for lactoferrin and 16 d for blood polymorphonuclear leukocytes. The rate of marrow regeneration was exponential and estimated to be 9-20% per d. The comparison between two different chemotherapy regimes showed that the initial reduction in lysozyme, in contrast to other measured variables, was significantly larger with the therapy that contained vincristine and glucocorticosteroids. This might reflect a reduction in lysozyme secretion in addition to the effects on the leukemic cell mass. We conclude that the measurements of lactoferrin, lysozyme and myeloperoxidase in serum under certain circumstances may be used to monitor the myelopoietic activity in the bone-marrow.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Effect of food on pharmacokinetics of chlorambucil and its main metabolite, phenylacetic acid mustard.

The influence of food intake on the pharmacokinetics of chlorambucil (C) and its cytotoxic metabolite, phenylacetic acid mustard (PAM), has been studied in man after oral doses of chlorambucil. The administration of chlorambucil with food resulted in slower absorption than when fasting. However, the area under the plasma concentration-time curve (AUC) was unaffected. The mean ratio AUCPAM/AUCC was 2.8 (range 1.4-7.1) under fasting and 3.3 (range 1.3-7.4) under nonfasting conditions. The metabolite very probably plays an important role in the cytotoxic effects observed after administration of C, since calculations show that a major fraction of the metabolite is eliminated by alkylation reactions.

Adult↗
PubMed1983

The peroxidase activity and cellular content of granule proteins in PMN during pregnancy.

The cellular content of myeloperoxidase (MPO), chymotrypsin-like cationic protein (CCP) and lactoferrin (LF) of isolated polymorphonuclear leucocytes (PMNs) from pregnant women were analysed by immuno-chemical methods. The cellular levels of MPO and CCP were unaltered during pregnancy while the cellular levels of LF were increased during pregnancy and post partum (P less than 0.01). Peroxidase activity within isolated PMN was analysed by two methods, a Guaiacol method and a Chemiluminescence method. The activity was found to be reduced during pregnancy. The reduction was explained by the reduction in eosinophil peroxidase which in turn was a consequence of a reduced number of circulating eosinophils during pregnancy.

Adult↗
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↗
PubMed1981

Comparison of daunorubicin and daunorubicin-DNA complex in the treatment of acute nonlymphoblastic leukemia.

Sixty consecutive patients, 15-60 years old, with ANLL were divided randomly into three groups for induction treatment with one of the following regimens: R1, daunorubicin (DNR) 1.5 mg/kg on day 1 + ARA-C 2 mg/kg body weight on days 1-5; R2, DNR 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8; R3, DNR-DNA complex 1.5 mg/kg on days 1 and 2 + ARA-C 2 mg/kg on days 4-8. Maintenance treatment consisted of monthly courses of DNR 1.5 mg/kg (R1, R2) or DNR-DNA 1.5 mg/kg (R3) combined with ARA-C 1 mg/kg on days 1-5, alternating with thioguanine 2 mg/kg PO on days 1-5 combined with ARA-C 1 mg/kg IV on days 1-5. Fourteen patients of 20 went into complete remission with R1, 13 or 18 with R2, and 15 of 22 with R3. The overall remission frequency was 70% and there was no significant difference between the different groups. The median time in first remission and the median survival time were 300 and 510 days, respectively, with R1; 335 and 495 days with R2; and 295 and 677 days with R3. There was no statistically significant difference between the groups treated according to the different regimens concerning the time in first remission. Survival was slightly better with R3 than with R1. Treatment with the DNR-DNA complex caused less pronounced thrombocytopenia and fewer 'minor' cardiac abnormalities than treatment with free DNR in the same dosage schedule.

Acute Disease↗
PubMed1978

T3 thyrotoxicosis in a child.

We report the case of a 5-year-old hyperthyroid boy with normal serum T4 levels are elevated serum T3 levels. The findings are diagnostic of T3 thyrotoxicosis, a condition that has been very infrequently reported in childhood. We postulate that low dietary iodine intake may be an etiologic factor in some cases of T3 thyrotoxicosis.

Child, Preschool↗