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Biomedical subjects

G Oberg

Publications and source records attributed to G Oberg.

At least 55 records · Page 3Linked to original sources
PubMed1992

In vivo distribution of [11C]-busulfan in cynomolgus monkey and in the brain of a human patient.

The in vivo distribution of the antileukemic agent busulfan labeled with the positron-emitting radionuclide carbon 11 was investigated in cynomolgus monkeys and in a human patient using positron emission tomography. After i.v. injection of the radiotracer, its regional uptake was monitored for about 1 h in the monkey's body and, in a separate experiment, in the monkey's brain. The concentration of radioactivity in the liver, which showed the highest levels of all the organs scanned, increased throughout the experiment and was 9-fold that in the brain at the end of the experiment. [11C]-Busulfan rapidly crossed the blood-brain barrier. The radioactivity peaked in both the cortex and the white matter showing a ratio of 1.25, at 3 min but declined quickly to yield a ratio of approximately 1 after 30 min. In the human brain, radioactivity in the cerebellum, cortex, and white matter reached a maximum within 5 min showing a cortex:white matter ratio of 1.6. The activity in the cortex declined to yield a ratio of 1 within 30 min. Of the delivered dose, 20% penetrated into the brain.

Adult↗
PubMed1992

Stimulation of NK cell, T cell, and monocyte functions by the novel immunomodulator Linomide after autologous bone marrow transplantation. A pilot study in patients with acute myeloid leukemia.

Immunostimulatory therapy is at present considered after autologous bone marrow transplantation (ABMT) in order to mimic the allogeneic graft-versus-leukemia effect and thereby reduce the relapse rate. In a pilot study, five adults with acute myeloid leukemia were treated with the new immunomodulator Linomide post-ABMT. Linomide (0.3 mg/kg/week orally) was given in cycles of three weeks followed by three weeks of rest for up to six months. During treatment periods cyclic increases of CD56+CD3- and CD16+ NK cells were observed in parallel with enhanced cytotoxic activity of patient cells against both the NK-sensitive K562 and NK-resistant Daudi cell lines. A cyclic increase of CD14+ monocytic cells was also recorded. The proliferative responses of patient cells to PHA and allogeneic cells (MLC) were enhanced during Linomide therapy. The in vitro production of TNF alpha, IFN gamma, and IL-1 followed the same cyclic increase during treatment periods. Side effects were generally mild, and no harmful effects on engraftment were seen. Linomide therapy after ABMT thus induces a broad immunostimulation that offers a potential benefit with regard to leukemia-free survival.

Adjuvants, Immunologic↗
PubMed1992

Oral ketoconazole prophylaxis for Candida infections during induction therapy for acute leukaemia in adults: more bacteraemias.

We determined whether ketoconazole prophylaxis might reduce Candida colonization and infections in adult patients with acute leukaemia. During first-remission induction therapy 50 patients were treated with 200 mg ketoconazole administered orally daily, while 57 patients received placebo in a double-blind, randomized trial. The duration of severe neutropenia (granulocytes less than 0.1 x 10(9) l-1) represented 36% of the study period in the ketoconazole group and 26% in the placebo group (P = 0.043). Although fewer patients presented with positive Candida surveillance cultures and serological evidence of Candida infection in the ketoconazole group compared to the placebo group, two candidaemias and one Trichosporum fungaemia were observed in the ketoconazole group. Moreover, significantly more bacteraemias were noted in the ketoconazole group (n = 37) than in the placebo group (n = 21) (P = 0.004). Thus, although oral ketoconazole prophylaxis might be associated with less Candida colonization and fewer seroconversions, it also resulted in more bacteraemias and longer duration of severe neutropenia, suggesting that caution should be exercised when ketoconazole (or related drugs) is given to this group of immunocompromised hosts.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Reduced regional cerebral blood flow in Huntington's disease studied by SPECT.

Regional cerebral blood flow (rCBF) was studied in 18 patients with Huntington's disease (HD) and 19 age- and sex-matched controls with high resolution single photon emission computerised tomography (SPECT), using Tc-99m-HMPAO. Significant reductions in tracer uptake were found in the caudate and lentiform nuclei (20 and 8%) and in the cerebral cortex, especially in the frontal and parietal areas (11-13%). No significant reductions were found in the thalamus, mesial temporal cortex, and occipital cortex. Fourteen patients had neuropsychological testing. Relationship between rCBF and cognitive function was tested by regression analysis. A linear relationship was found between test scores of Wisconsin Card Sorting Test, Picture Arrangement Test and blood flow in the caudate nucleus. Other tests of cognitive function (Block Design Test, Face and Word Recognition Test, Street Fragmented Pictures Test, and Similarities Test) correlated better with flow in the cortical regions believed to be involved in solving those particular tests. These findings indicate, that blood flow is reduced in both cortical and subcortical structures in symptomatic HD, and that both reductions in cortical and subcortical blood flow may be related to cognitive function in HD.

Adult↗
PubMed1992

Ceftazidime as initial therapy in febrile patients with acute leukemia during induction chemotherapy. Leukemia Group of Middle Sweden.

We studied the efficacy of ceftazidime as initial monotherapy in 82 adult patients with acute leukemia who developed 123 febrile episodes during induction chemotherapy. 88% of the patients survived their febrile episode(s), whereas 10% died of infection. When assessed at 72 h after initiation of treatment (early evaluation), 43/123 episodes (35%) had been successfully treated with ceftazidime. These 43 favourable responses were seen in 15/47 (32%) microbiologically documented infections, 20/46 (43%) clinically defined infections, and 8/30 (27%) fever of unknown origin (FUO). At the resolution of fever (late evaluation) 115 episodes were evaluable, and 48% had responded successfully to ceftazidime. Successful treatment was most frequently observed in FUO, 18/29 (62%). In contrast, only 19/44 (43%) microbiologically documented infections and 18/42 (43%) clinically defined infections were cured during ceftazidime treatment. In bacteremia the response rate was only 8/26 (31%). Thus, this study shows that although ceftazidime can be safely used for initial empirical monotherapy in neutropenic leukemia patients, the need for therapy modification is high and few patients with serious infections are cured with ceftazidime alone.

Adolescent↗
PubMed1992

Thyroid function after autologous bone marrow transplantation.

Thyroid function was prospectively analysed in 111 consecutive patients in relation to autologous bone marrow transplantation (ABMT). Median follow-up time was 12 (range 3-60) months. As part of the conditioning treatment 58 patients had received total body irradiation (TBI) as a single dose of 7.5 Gy (dose rate 0.15 Gy/min). Thyroxine, triiodothyronine, thyrotropin (TSH) and thyroid antibodies were analysed before ABMT, every third month during the first year afterwards and then once annually. Thyroid dysfunction was seen in 20 patients (after TBI in 16, after non-TBI treatments in four). Five of these, all treated with TBI, developed primary hypothyroidism and in 15 compensated hypothyrosis, transient in eight (40%), was seen. There was a highly significant (p less than 0.001) increase, within the normal range, in median TSH level, prior to ABMT compared with 1 year following ABMT. In patients who developed thyroid dysfunction, the TSH level before ABMT was significantly higher (p less than 0.001) than in those who remained euthyroid. In four patients persistent elevated thyroid antibody titers appeared and in two of them hypothyrosis developed. No correlation between thyroid dysfunction and age was noted. The findings are similar to those after allogeneic BMT described by others.

Adolescent↗
PubMed1992

Immunity to and immunization against measles, rubella and mumps in patients after autologous bone marrow transplantation.

Humoral immunity to measles, rubella and mumps was studied in 63, 36 and 16 patients 1, 2 and 3 years, respectively after autologous bone marrow transplantation (ABMT). Serologic examination was performed using antibody-ELISA. One year after ABMT, 7/57 patients (12%) who were seropositive to measles before ABMT, became seronegative, 8/44 (18%) to rubella and 3/51 (6%) to mumps. Among patients who were retested at 2 and 3 years, three more patients became seronegative to measles, one to rubella, and three to mumps. Nine of 12 children who had previously been immunized against measles were seropositive before ABMT, 3/7 to rubella and 5/7 to mumps, respectively. After ABMT, 5/9 became seronegative to measles, none to rubella and 2/5 to mumps. Six seronegative children were immunized with a live trivalent attenuated measles, mumps, and rubella vaccine 1 to 2 years after ABMT. Two children seroconverted to measles, six to rubella, and four to mumps. No side effects were observed. Most adult patients who have had the diseases of measles, rubella, or mumps naturally remain seropositive, while children who have been immunized commonly lose their immunity after ABMT.

Adolescent↗
PubMed1991

Pharmacokinetics of high-dose busulphan in relation to age and chronopharmacology.

Busulphan levels in plasma were measured in 27 patients during conditioning therapy (1 mg/kg x 4 for 4 days) before bone marrow transplantation. The mean minimal concentration found in children aged less than 5 years (237 ng ml-1) was lower than that observed in adults or older children (607 and 573 ng ml-1, respectively). The AUC for the last dose was significantly lower in young children (2.315 h ng ml-1) than in adults or older children (6,134 and 5,937 h ng ml-1, respectively). The elimination half-life for the last dose in young children was shorter (2.05 h) than that in either adults (2.59 h) or older children (2.79 h). When the AUC was normalized for body surface area, the difference between young children and the other groups was smaller but remained statistically significant. The total body clearance was significantly higher in young children (7.3 ml min-1 kg-1) as compared with both older children and adults (3.02 and 2.7 ml min-1 kg-1, respectively). The plasma levels of busulphan showed circadian rhythmicity, especially in young children. The concentration measured during the night in some patients was up to 3-fold that observed during daytime. We conclude that the busulphan dosage for children must be reconsidered and that further studies are urgently needed to develop an optimal therapy.

Adolescent↗
PubMed1991

Regeneration of CALLA (CD10+), TdT+ and double-positive cells in the bone marrow and blood after autologous bone marrow transplantation.

In this prospective study we investigated the frequency of CD10+, TdT+ and CD10+TdT+ mononuclear cells in the bone marrow (BM) and peripheral blood (PB) before and after autologous bone marrow transplantation (ABMT). 49 patients treated for acute lymphoblastic or myeloblastic leukaemia, malignant lymphoma or multiple myeloma were included. A significant increase in CD10+ cells occurred in BM in both children and adults after ABMT. In children, we also found a significant increase in CD10+ cells in PB. In individual patients remaining in remission, up to 34% CD10+ cells having a normal Ig kappa/lambda light chain ratio were recorded after ABMT. In children, the percentage of TdT+ and CD10+ TdT+ cells increased significantly in BM. In most cases the CD10/TdT-ratio was greater than 1.0, but during early regeneration after ABMT this ratio was less than 1.0 in several patients remaining in complete remission. In patients remaining in remission, CD10+TdT+ cells were detected in the blood in only 2 out of 140 samples tested, and the proportion of these cells never exceeded 0.03%. We conclude that quantitation of CD10+TdT+ cells in peripheral blood is helpful in the evaluation of complete remission in patients treated for pre-B-ALL.

Adult↗
PubMed1991

Renal function after autologous bone marrow transplantation.

Seventy-two out of 102 consecutive patients autografted for various hematologic and lymphoid malignancies had a relapse-free survival of greater than 6 months after autologous bone marrow transplantation (ABMT) and were evaluated for long-term effect of the treatment on the renal function. The myeloablative therapy included total body irradiation (TBI) in a single fraction of 7.5 Gy in 41/72 patients. Mean glomerular filtration rate (GFR) showed a significant decrease (p less than 0.01) and serum creatinine and serum urea an increase (p less than 0.05) 6 months after ABMT. Twelve of 72 patients (17%) developed renal dysfunction defined as greater than 25% decrease in GFR, in most cases accompanied by hematuria and proteinuria. Onset was 3-6 months after ABMT. Some patients have later improved considerably, but others continue to deteriorate in renal function. The single most important risk factor for renal dysfunction after ABMT was irradiation. Renal damage was most frequent in lymphoma patients conditioned with BEAC (carmustine [BCNU], etoposide, cytarabine, cyclophosphamide) followed by irradiation, suggesting that this drug combination might have potentiated the toxicity of irradiation. Nephrotoxic antibiotics probably contributed to renal damage in individual cases. Young age did not appear to be a risk factor. Our data indicate that combined treatment with BEAC and TBI should be used with caution and that renal function should be monitored in all patients after bone marrow transplantation to detect any new toxicity patterns of the various conditioning regimens currently used.

Adolescent↗
PubMed1990

Treatment of myelodysplastic syndromes with retinoic acid and 1 alpha-hydroxy-vitamin D3 in combination with low-dose ara-C is not superior to ara-C alone. Results from a randomized study. The Scandinavian Myelodysplasia Group (SMG).

63 evaluable patients with myelodysplastic syndromes (MDS) and 15 with acute myelogenous leukemia (AML) were randomized between low-dose ara-C (arm A) and low dose ara-C in combination with 13-cis-retinoic acid (13-CRA) and 1 alpha-hydroxy-vitamin D3 (1 alpha D3) (arm B). 69 patients were evaluable and 18 (26.1%) responded to therapy. The addition of 13-CRA and 1 alpha D3 had no positive influence on survival of the patients, remission rates or duration of remissions. 12/27 patients in arm A and 6/29 patients in arm B progressed from MDS to AML during the course of the study (p = 0.0527). Arm B gave significantly more side-effects than arm A (p = 0.005). Therapeutic effects of 13-CRA and 1 alpha D3 on MDS is not supported by this study. However, an inhibiting effect on AML development in some MDS subgroups cannot be excluded.

Aged↗
PubMed1990

Impaired glucose tolerance after autologous bone marrow transplantation.

In this study we investigated glucose tolerance in relation to autologous bone marrow transplantation (ABMT). In 13 adult patients with acute myeloblastic (AML) or lymphoblastic (ALL) leukaemia in complete remission (CR), intravenous glucose tolerance test (IVGTT) was performed 1 month before and 6 months after ABMT. Patients with AML in CR received, as myeloablative therapy, cyclophosphamide combined with busulphan or total body irradiation (TBI). ALL patients received total body irradiation in combination with vincristine, daunorubicin, Ara-C, cyclophosphamide and prednisone. Before ABMT all patients, in spite of the intensive chemotherapy given for remission induction and consolidation, had a normal glucose tolerance. However, 6 months after the transplantation the k-value (rate of glucose elimination) for this group of patients had decreased (p less than 0.01). The trend towards impaired glucose tolerance was correlated with lower peak insulin values during IVGTT (p less than 0.05). Thus, the myeloablative therapy in connection with ABMT caused an impairment of pancreatic beta-cell function. No patient has hitherto developed clinical diabetes mellitus.

Adult↗
PubMed1989

Pharmacokinetic and metabolic studies of high-dose busulphan in adults.

The pharmacokinetics of high-dose busulphan was studied in adult patients with acute myeloblastic leukaemia after oral doses of 1 mg.kg-1 every 6 h for 4 days. The mean steady-state plasma concentration was 1080 ng/ml-1 during the treatment. Individual steady-state concentrations after the last dose on average were 32% lower than those predicted from total AUC measurements following the first dose. Mean elimination half-life in plasma was 2.3 h after the last dose and 3.4 h after the first dose which suggests that busulfan may increase its own metabolic rate on repeated treatment. The cerebrospinal fluid/plasma concentration ratio of busulphan was 1.3. Busulphan showed insignificant protein binding in plasma (7.4%). About 2% of the dose was excreted unchanged in the urine. For the first time sulpholane, 3-hydroxysulpholane and tetrahydrothiophene 1-oxide were identified as urinary metabolites of busulphan in man.

Adult↗
PubMed1989

B lymphocyte regeneration in marrow and blood after autologous bone marrow transplantation: increased numbers of B cells carrying activation and progression markers.

The reconstitution of B cells in the bone marrow and peripheral blood was prospectively studied in 27 patients undergoing autologous bone marrow transplantation (ABMT). No major differences in B cell regeneration patterns were recorded between patients receiving marrows purged of B cells (anti-CD10 + 19; n = 17) and patients receiving unpurged marrows (n = 10). Compared with healthy controls, elevated absolute and relative numbers of B cells were recorded in the blood and marrow at +6 and +12 months in both groups of patients. CD23+ B cells were severely depressed during the first three months post ABMT, indicating immaturity. A twofold increase in B cells carrying the activation marker 4F2 was recorded in the marrow at +1 month. Serum immunoglobulin levels (IgG, IgA, IgM) were within low-normal range throughout the study. The depressed B cell responses reported after allogeneic and autologous BMT could in part be explained by the low expression of the CD23 antigen on B cells after such therapy.

Antigens, CD19↗
PubMed1989

B-cell reconstitution after autologous bone marrow transplantation: increase in serum CD23 ("IgE-binding factor") precedes IgE and B-cell regeneration.

The serum levels of IgE and the soluble cleavage product of CD23 (sCD23) were prospectively monitored for up to 1 year after transplantation in 34 patients who underwent autologous (n = 33) or syngeneic (n = 1) bone marrow transplantation (BMT). In 25 patients (74%), a transient IgE peak (two- to 2,750-fold increase) appeared in the serum 3 to 4 weeks after BMT. In 18 patients (51%), a two- to 125-fold increase in sCD23 coincided with the IgE peak. In only three patients was a sCD23 peak observed without a concomitant increase in IgE. The sCD23 increment preceded the IgE peak in each individual case. During the period of increased sCD23 serum levels, the absolute numbers of circulating B cells and other cell types expressing surface CD23 were extremely low. The biologic significance of these findings is discussed in light of present knowledge of regulation of B-cell growth and differentiation with special reference to the role of sCD23 as a multifunctional cytokine.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Regeneration of functional and activated NK and T sub-subset cells in the marrow and blood after autologous bone marrow transplantation: a prospective phenotypic study with 2/3-color FACS analysis.

The phenotypic reconstitution of lymphoid cells in the bone marrow and peripheral blood was examined prospectively in 27 patients who underwent autologous bone marrow transplantation (ABMT) for leukemia/lymphoma. Patterns of activation within NK and T cell subsets as well as T sub-subsets were studied with monoclonal antibodies in two- and three-color FACS analysis. NK-like cells (CD16+) were found to be increased in the peripheral blood and bone marrow after ABMT. The expression of two activation markers, 4F2 and HLA-DR, was sustainedly increased within this subset. High numbers of CD4+ and CD8+ T cells carrying surface HLA-DR were found early after ABMT both in blood and marrow. The T suppressor inducer cell sub-subset (CD45R+ CD4+) was severely depressed in both the blood and marrow 6-9 months post-ABMT. Using three-color FACS analysis, half of this T sub-subset was shown to express HLA-DR+. The levels of T suppressor effector-like cells (CD11+ CD8+) remained within the normal range in both peripheral blood and bone marrow during follow-up. The HLA-DR expression was elevated and equally distributed between the CD11- CD8+ and CD11+ CD8+ sub-subset cells. There was no major impact of marrow T cell purging or CMV carrier status on the phenotypic NK/T cell reconstitution. The present results provide an immune phenotypic basis for the suggested generation of anti-leukemic NK-like and T suppressor-like activity after ABMT.

Adolescent↗
PubMed1989

Cerebrospinal fluid and plasma concentrations of busulfan during high-dose therapy.

A patient with acute myeloblastic leukemia received high-dose busulfan (1 mg/kg by mouth every 6 h for 4 days) as myelo-ablative therapy for autologous bone marrow transplantation. Rapid entry of busulfan into the cerebrospinal fluid (CSF) was observed. Plasma and CSF concentrations of busulfan were comparable during the 4 days of treatment. The elimination half-lives of busulfan in plasma and CSF were 2.6 h and 2.8 h respectively during the first 12 h after the last dose.

Bone Marrow Transplantation↗