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P Muus

Publications and source records attributed to P Muus.

At least 37 records · Page 2Linked to original sources
PubMed1995

Immigration--mismatches in labour, housing and space: the effects of immigration of several nationalities with regard to the Netherlands.

"In the Netherlands, the sharp recent increase of the number of refugee immigrants (asylum seekers) runs parallel to increased numbers of immigrants of other types. Therefore, at least five types of immigrants should still be distinguished (labour migrants, migrants from former colonies, from EU countries, from other rich countries, and asylum seekers). Their spatial orientation in the Netherlands (urban, suburban, rural), by choice or by constraint, is the main focus of this study. The outcomes of the immigration processes have been confronted with general and spatial characteristics of the labour market and housing market. Matches and mismatches are discussed."

Demography↗
PubMed1994

In vitro response of blasts to IL-3, GM-CSF, and G-CSF is different for individual AML patients: factors that stimulate leukemic clonogenic cells also enhance Ara-C cytotoxicity.

In vivo, growth factors are currently investigated for their capacity to trigger leukemic stem cells into cycle and thus overcome kinetic drug resistance. In this study, the susceptibility of leukemic clonogenic cells to individual growth factors was related to cytosine-arabinoside (Ara-C) sensitivity. The effects of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (G-CSF), granulocyte colony-stimulating factor (G-CSF), and combinations of these recombinant hematopoietic factors were tested on blast cells of nine acute myeloid leukemia (AML) patients. Growth factor responses were assessed in semi-solid clonogenic assay and in a 10-day liquid culture followed by clonogenic assay. Heterogeneity in growth factor response was observed in both test systems, resulting in a variable pattern for individual leukemias. In the majority of cases (six of nine) the response patterns in the semi-solid and liquid cultures were divergent. To test the Ara-C sensitivity, leukemic blasts were exposed in liquid to various concentrations of Ara-C in the absence and presence of preselected growth factors. After 10 days, the number of surviving leukemic colony-forming cells (CFU-L) was assessed. Exposure to Ara-C in the presence of optimal stimulatory factor(s) resulted in a 3- to 1000-fold increase of the Ara-C toxicity in seven patients. The Ara-C concentrations resulting in 50% inhibition of clonogenicity (ID50) were 0.48-123 x 10(-8) M Ara-C in the absence of stimulatory growth factors, versus only 0.12-0.40 x 10(-8) M Ara-C in the presence of these factors. In two patients, addition of one or more factors neither increased the number of CFU-L in liquid nor enhanced the Ara-C toxicity. Even in the absence of growth factors the ID50 values in these cases were as low as 0.20 and 0.28 x 10(-8) M Ara-C and in the same range as the ID50 values observed with maximum growth factor stimulation in the other seven patients. These results indicate that Ara-C cytotoxicity can be enhanced by individually selected, clonogenic cell growth-promoting hematopoietic factors.

Adolescent↗
PubMed1994

Role of allogenic bone marrow transplantation in adolescent or adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma in first remission.

Sixty-nine adolescents and adults 15-51 years of age with untreated acute lymphoblastic leukaemia (ALL, 54 patients) or lymphoblastic lymphoma (LL, 15 patients) were referred for intensive antileukaemic therapy. Patients were treated according to one of two protocols. Both included induction and consolidation with vincristine, prednisone, daunorubicin, cyclophosphamide, Ara C and asparaginase. Fifty-eight patients achieved complete remission within 8 weeks of chemotherapy. One additional patient entered remission after allogeneic BMT. Altogether 86% of the patients achieved CR. Thirty-three patients are alive, corresponding to an actuarial survival of 48 +/- 6% at 5 years after start of therapy. Survival from time of achievement of CR is 53 +/- 7% at 5 years and disease-free survival (DFS) is 52 +/- 7%. Consolidation treatment was given to all patients except one. An HLA-identical sibling was identified for 30 patients (45%). Twenty-two patients were scheduled to be transplanted with marrow from an HLA-identical sibling. The survival and DFS in these 22 patients was 58 +/- 11% at 5 years. DFS was not significantly different compared with the DFS of the eight patients who received an auto-BMT and the 26 patients treated with maintenance chemotherapy. DFS at 5 years was 63 +/- 17% and 40 +/- 10%, respectively. We also evaluated the influence of the presence of an HLA-identical sibling on the treatment outcome of all patients alive 12 weeks after initiation of remission-induction therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Regulation of the expression of mitochondrial proteins: relationship between mtDNA copy number and cytochrome-c oxidase activity in human cells and tissues.

The relationship between the relative amounts of nuclear and mitochondrial genes for cytochrome-c oxidase subunits and their transcripts and cytochrome-c oxidase activity was investigated in several human tissues and cell lines to get more insight into the regulation of the expression of this mitochondrial enzyme complex. The results show: (1) a wide range of mtDNA copy numbers; (2) constant ratios between the steady-state levels of the transcripts for the various cytochrome-c oxidase subunits, and (3) large variations in cytochrome-c oxidase activity in different tissues and cell lines that could not be related to the differences in mtDNA copy number. We conclude that the transcription of genes for both mitochondrial and nuclear cytochrome-c oxidase subunits is regulated coordinatedly, but also that the mtDNA copy number plays a minor role in determining differences in cytochrome-c oxidase activity between different cell and tissue types.

Cell Nucleus↗
PubMed1993

Proliferation patterns in acute myeloid leukemia: leukemic clonogenic growth and in vivo cell cycle kinetics.

In a prospective study of 33 newly diagnosed patients with acute myeloid leukemia (AML), we analyzed the relationship of proliferation parameters with clinical parameters, response to induction therapy, and survival. The median follow-up was 26 months. The proliferative capacity of the leukemic progenitor cells was studied using colony-forming assays (number of colony-forming units, growth pattern, and spontaneous clonogenic growth capacity). The cell kinetic parameters of the bone marrow blasts were determined by in vivo labeling with iododeoxyuridine and subsequent flow cytometry: labeling index (LI), DNA synthesis time (Ts), potential doubling time. No or only weak relationships were observed between the experimental and clinical parameters such as age, sex, % blasts, white blood cell count, FAB subtype, cytogenetics, and % CD 34+ cells. This suggests that clonogenic growth and cell cycle kinetics of bone marrow blasts are independent cell biologic properties of AML. No association between the proliferation parameters and induction response rate was noticed. Analysis of the overall survival and event-free survival revealed trends to longer survival rates in patients with a below-median LI (< or = 7.6%) and below-median Ts value (< or = 14.3 h). These trends were more pronounced in the group of de novo AML (n = 23), where the prolonged event-free survival in patients with below-median Ts reached statistical significance (p = 0.02). None of the other parameters appeared significantly correlated with survival, although there was a trend to longer survival rates in patients who had no spontaneous clonogenic growth capacity (p = 0.13). In conclusion, proliferation parameters in leukemic cells provide additional information on the cell biologic characteristics of AML, and these parameters may have prognostic value for response and duration of survival in AML.

Adult↗
PubMed1993

Failure of clindamycin to influence the course of severe oromucositis associated with streptococcal bacteraemia in allogeneic bone marrow transplant recipients.

33 consecutive allogeneic bone marrow transplant recipients who were likely to develop streptococcal bacteraemia were treated for 5 days with clindamycin (900 mg i.v. t.d.s) and ceftazidime (2 g t.d.s.) for the initial management of fever associated with severe oral mucositis. Bacteraemia due to 'viridans' streptococci was encountered in 23 cases (70%) as mucositis progressed to peak severity and occurred a day before fever in 8 cases. At the end of treatment with clindamycin only 2 patients had defervesced although the streptococci were successfully eradicated. C-reactive protein (CRP) levels continued to rise in 18 cases and declined by more than 10% in only 7 cases. Severe oromucositis rather than infection appeared to induce an acute phase response with fever suggesting bacteraemia due to 'viridans' streptococci to have been a consequence of mucosal damage. Indeed, oromucositis was the only primary focus of inflammation in 22 patients and only after its resolution did both fever and CRP levels diminish. By then, patients had also begun to recover from granulocytopenia. These data indicate that rather than including a specific antimicrobial like clindamycin in an empirical regimen, it would be more beneficial to evolve strategies that minimise mucosal damage in this patient population.

Adolescent↗
PubMed1993

Preliminary results with 5-aza-2'-deoxycytidine (DAC)-containing chemotherapy in patients with relapsed or refractory acute leukemia. The EORTC Leukemia Cooperative Group.

Twenty two patients with acute relapsed leukemia (AML 20, ALL 2) were treated with 5-aza-2'-deoxycytidine (DAC) and either m-amsacrine or idarubicin. DAC was administered as a 6-h infusion, every 12 h for 6 days in combination with either m-amsacrine (120 mg/m2) as a 1-h infusion on days 6 and 7 (n = 19) or idarubicin (12 mg/m2) as a 15-min infusion on days 5, 6 and 7 (n = 3). Thirteen patients (59%) achieved a complete remission. The treatment was complicated by nausea, vomiting, diarrhoea with signs of peritonitis (n = 9), weight loss (n = 7), cerebellar or cerebral toxicity (n = 2), gastrointestinal bleeding (n = 3), liver toxicity (n = 2) and prolonged myelosuppression. Median duration of remission was 4 months (range 1-30). The preliminary data show that DAC is an anti-leukemic agent, comparable to high dose Ara-C with comparable severe toxicity.

Acute Disease↗
PubMed1993

Allogeneic bone marrow transplantation for leukemia with marrow grafts treated by counterflow centrifugation.

Eighty consecutive patients were transplanted with human leukocyte antigen (HLA)-identical sibling marrow for acute myelogenous leukemia (AML, N = 29), acute lymphoid leukemia (ALL, N = 23), or chronic myelogenous leukemia (CML, N = 28). Donor marrow was depleted of lymphocytes using counterflow centrifugation. Median age of the recipients was 31 years. Pretransplant conditioning consisted of cyclophosphamide and fractionated total body irradiation (TBI). Graft failure occurred in 4 of 77 evaluable patients (5%). The probability of acute graft-versus-host disease (GVHD) > or = grade 2 at day 100 after transplantation was 15%. The projected 3-year estimate of extensive chronic GVHD was 12%. The projected 3-year probability of relapse was 30% in transplants for AML in first complete remission (CR1), 35% after transplantation for ALL in CR1, and 38% after transplantation for CML in first chronic phase (CP1). The projected 3-year probability of leukemia-free survival (LFS) was 56% after transplantation for AML-CR1, 42% in patients transplanted for ALL-CR1, and 49% after transplantation for CML-CP1. The chance of relapse was significantly reduced in a cohort of 72 standard risk patients conditioned with a regimen intensified by the addition of anthracyclines. This resulted in DFS at 4 years after BMT of 63% compared to 39% in a historical control group. Enrichment of the donor marrow with NK-cells did not increase the incidence of GVHD, but did neither decrease the relapse rate after BMT. In bone marrow transplantation for leukemia, counterflow centrifugation is a useful technique for the prevention of GVHD. Further efforts should be made to reduce relapse-rate, particularly in high risk patients.

Adolescent↗
PubMed1993

Idarubicin-related side effects in recipients of T-cell-depleted allogeneic bone marrow transplants are schedule dependent.

The influence of three different dosage schedules of anthracycline (idarubicin or daunorubicin)-intensified preparative therapy prior to T-cell-depleted allogeneic bone marrow transplantation (BMT) on (1) the severity and duration of oral toxicity (mucositis), (2) the duration of bone marrow aplasia, and (3) overall survival, relapse, and disease-free survival was studied in 99 BMT patients with standard- or high-risk hematologic malignancies. A further 146 patients who did not receive the anthracycline-intensified conditioning served as (historic) controls. All patients received cyclophosphamide (total dose, 120 mg/kg) on days -6 and -5 and total body irradiation on days -2 and -1 prior to BMT. The 99 patients who received the anthracycline-intensified preparative regimen were given either idarubicin (total dose, 42 mg/m2; n = 88) or daunorubicin (total dose, 156 mg/m2; n = 11) by continuous intravenous infusion between days -7 and -1 prior to BMT in 59 cases (cohort 1), on days -8 and -7 in 17 cases (cohort 2), and on days -12 and -11 in 23 cases (cohort 3). The occurrence of severe oral mucositis and delayed bone marrow recovery was schedule dependent, being substantially lower with earlier administration of the anthracycline-intensified regimen on days -12 and -11 before BMT (cohort 3), in comparison with later administration (cohorts 1 and 2). Plasma drug and metabolite concentrations were measured in 11 patients who received idarubicin. At the time of allogeneic bone marrow infusion (day 0), patients in cohorts 1 and 2 had plasma concentrations of idarubicin and idarubicinol (its active metabolite) in the range of in vitro cytotoxicity. However, in cohort 3, plasma concentrations on day 0 were much lower, which correlated with the lower maximum intensity and shorter duration of mucositis in these patients. In terms of overall survival, relapse rate, and disease-free survival in standard-risk patients, the anthracycline-intensified regimen proved to be very effective. Transplant-related mortality was 25% in the anthracycline group compared with 32% in the controls. The probability of relapse also was significantly less in the anthracycline group in comparison with controls (17% v 46%; P < .001), and the probabilities of long-term overall and disease-free survival were significantly greater (71% v 37% [P < .01] and 63% v 32% [P < .01], respectively). Only three patients in the idarubicin group experienced cardiotoxicity (one in each cohort); the causative relationship with anthracyclines was considered likely in one, possible in one, and doubtful in the third.

Adolescent↗
PubMed1992

A scheme for daily monitoring of oral mucositis in allogeneic BMT recipients.

A system was developed for scoring oral mucositis in order to investigate its connection with fever and bacteraemia due to 'viridans' streptococci. A series of 42 allogeneic bone marrow transplant recipients given demethoxydaunorubicin and total body irradiation for conditioning therapy were monitored daily for the presence of lesions, erythema, oral oedema, pain and dysphagia, each of which was graded numerically at four levels. These values were added together to yield a daily mucositis score (DMS) with a scale of 0-15. Mucositis developed shortly after transplant and progressed within a few days to grade III (WHO grade 3-4) in the majority of patients. Bacteraemia due to 'viridans' streptococci was documented in 64% of cases and the organisms were first detected as fever developed and mucositis approached its peak. The WHO scheme defined mucositis as either absent or grade 3-4 corresponding to a DMS of 4 or 5, whereas a grading system based on the most pronounced sign or symptom resulted in three grades of severity which corresponded to a DMS of less than or equal to 4, 5-9 and greater than or equal to 10 respectively. However, only the DMS permitted monitoring of mucositis through all its stages of development. The scheme therefore offers the potential for exploring causal relationships between mucosal damage, granulocytopenia, fever and bacteraemia and can be included as an independent measure in studies of prevention and therapy of complications related to mucositis.

Adolescent↗
PubMed1991

1-beta-D-arabinofuranosylcytosine (Ara-C) enhances mitochondrial activities in human leukaemic cells.

1-beta-D-Arabinofuranosylcytosine (Ara-C) at a concentration which inhibits nuclear-DNA reduplication (0.05 microM), enhances mitochondrial activities like respiration, in cell of a human leukaemic cell line Molt 4. While the specific activity of cytochrome c oxidase doubles in the course of the G1 phase of the cell cycle in control cells, in the presence of Ara-C G1 phase cells begin to increase the enzyme activity earlier and show a 3-fold rise of the enzyme activity in the same period of time. This is explained by an enhanced expression of the mitochondrial genome: the concentration of transcripts for the mitochondrially encoded subunit II of cytochrome c oxidase increases. Inhibition of mitochondrial protein synthesis abolishes the Ara-C induced effect on the specific activity of cytochrome c oxidase activity. The concentration of transcripts of the nuclearly encoded subunit IV of cytochrome c oxidase is the same as in control cells, and also the specific activity of the mitochondrial enzyme citrate synthase, which is exclusively encoded on nuclear-DNA, is not affected by Ara-C. Dysregulation in time and intensity of the expression of the mitochondrial relative to the nuclear genome may impair cell function and reflect a till now neglected mechanism of Ara-C cytotoxicity.

Adenosine Diphosphate↗
PubMed1991

Prolonged exposure to cytosine arabinoside in the presence of hematopoietic growth factors preferentially kills leukemic versus normal clonogenic cells.

We investigated the cytotoxic effect of the cell cycle-specific agent cytosine arabinoside (Ara-C) on clonogenic leukemic and normal bone marrow cells. To overcome kinetic resistance and to increase cytotoxicity, the cells were exposed to Ara-C in liquid culture medium for extended time periods, that is, 5 and 10 days. Subsequently the number of surviving clonogenic cells was determined in a semi-solid assay. All cultures were stimulated with the combination of recombinant human interleukin 3 (rhIL-3), granulocyte-macrophage colony-stimulating factor (rhGM-CSF), and granulocyte colony-stimulating factor (rhG-CSF) to induce optimal cell proliferation. In comparison to normal clonogenic bone marrow cells (granulocyte-macrophage colony-forming units, CFU-GM) 5-day Ara-C exposure resulted in an equal to a slightly more effective kill of leukemic colony-forming cells (CFU-L). The Ara-C dose resulting in 50% inhibition (ID50) was 1.6 +/- 1.6 x 10(-8) M for CFU-L (n = 9) and 6.7 +/- 4.3 x 10(-8) M for CFU-GM (n = 4, p = 0.096). Prolongation of the Ara-C exposure time from 5 to 10 days increased the cytotoxicity towards the majority of the leukemic clonogenic cells (ID50: 0.8 +/- 0.6 x 10(-8) M) but not towards CFU-GM (ID50: 5.7 +/- 2.8 x 10(-8) M). Overall, significantly more leukemic clonogenic cells than normal CFU-GM were killed after 10 days of exposure to Ara-C (p = 0.039). These results indicate that leukemic clonogenic cells can be eradicated preferentially by prolonged exposure to low dosages of Ara-C in the presence of hematopoietic growth factors with relative preservation of the normal hematopoietic progenitor cells.

Bone Marrow↗
PubMed1990

Intensive antileukemic treatment of patients younger than 65 years with myelodysplastic syndromes and secondary acute myelogenous leukemia.

Intensive antileukemic treatment was evaluated in 22 patients with secondary acute myelogenous leukemia (sAML) and 14 patients with myelodysplastic syndrome (MDS). Results of combination remission-induction chemotherapy were compared with 126 patients contemporarily treated for primary AML. The duration of hypoplasia, induced by remission induction chemotherapy, tended to be longer in the sAML and MDS patients when compared to de novo AML, but reached significance only for the duration of thrombocytopenia: 26 days versus 18 days (P less than 0.01). The number of hypoplastic deaths during remission-induction chemotherapy of patients with sAML and MDS was low. Four of the 36 patients treated for sAML or MDS died during hypoplastic phases induced by remission-induction chemotherapy. The complete remission (CR) rates were similar in primary AML (67%), sAML (62%), and MDS (64%). The CR rates of patients younger than 45 years were 75% for de novo AML, 75% for sAML, and 71% for MDS. Remission rates in patients older than 45 years were identical in the three subgroups but significantly (P less than 0.005) inferior to those obtained in younger patients: 56%, 50%, and 57%, in de novo AML, sAML, and MDS, respectively. The remission duration without bone marrow transplant (BMT) was significantly shorter (P less than 0.01) in MDS and sAML when compared with primary AML. Long-lasting CR in MDS and sAML was only obtained in three of the six patients treated with allogeneic BMT. Intensive antileukemic therapy could be considered in young patients with MDS and life-threatening cytopenias or patients with sAML.

Adult↗
PubMed1990

Allogeneic bone marrow transplantation for leukemia with marrow grafts depleted of lymphocytes by counterflow centrifugation.

Eighty consecutive patients were transplanted with human leukocyte antigen (HLA)-identical sibling marrow for acute myelogenous leukemia (AML, N = 29), acute lymphoid leukemia (ALL, N = 23), or chronic myelogenous leukemia (CML, N = 28). Donor marrow was depleted of lymphocytes using counterflow centrifugation. Median age of the recipients was 31 years. Pretransplant conditioning consisted of cyclophosphamide and fractionated total body irradiation (TBI) with a low (4.1 +/- 0.3 cGy/min) or high (13.1 +/- 1.6 cGy/min) midline average dose rate. In 43 patients, cytosine-arabinoside or anthracyclines were added to the conditioning regimen. Immunoprophylaxis posttransplant consisted of methotrexate (MTX) alone, cyclosporine A (CsA) in combination with MTX, or CsA alone; two patients received no immunoprophylaxis at all. Graft failure occurred in 4 of 77 evaluable patients (5%). The probability of acute graft-versus-host disease (GVHD) greater than or equal to grade 2 at day 100 after transplantation was 15%. The projected 3-year estimate of extensive chronic GVHD was 12%. Only three patients died of cytomegalovirus-interstitial pneumonitis. The projected 3-year probability of relapse was 30% (95% confidence interval [CI], range 8% to 53%) in transplants for AML in first complete remission (CR1), 35% (95% CI, 1% to 69%) after transplantation for ALL in CR1, and 38% (95% CI, 2% to 74%) after transplantation for CML in first chronic phase (CP1). The projected 3-year probability of leukemia-free survival (LFS) was 56% (95% CI, 35% to 77%) after transplantation for AML-CR1, 42% (95% CI, 16% to 69%) in patients transplanted for ALL-CR1, and 49% (95% CI, 18% to 80%) after transplantation for CML-CP1. After transplantation for AML-CR1, ALL-CR1, or CML-CP1, the median follow-up time for leukemia-free survivors was 31+, 30+, and 21+ months, respectively. Probabilities of relapse, survival, and LFS in AML-CR1 and ALL-CR1 transplants were comparable with those reported in recipients of untreated grafts. In patients transplanted for CML-CP1, probability of relapse was higher and probability of LFS was lower than in recipients of untreated grafts. In transplants for leukemia in CR1 and CP1, preparative regimen and immunoprophylaxis posttransplant were not associated significantly with the probability of acute GVHD greater than or equal to grade 2, extensive chronic GVHD, relapse, survival, or LFS. In bone marrow transplantation for leukemia, counterflow centrifugation is a useful technique for the prevention of GVHD.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1989

Intensive chemotherapy for patients with myelodysplastic syndromes and acute myelogenous leukaemia younger than 65 years.

Intensive antileukemia treatment was evaluated in 22 patients with untreated secondary acute myelogenous leukemia (sAML) and 14 patients with bad prognosis myelodysplastic syndrome (MDS). Results of combination remission-induction chemotherapy were compared with 126 patients treated for primary AML. The duration of hypoplasia tended to be longer in the sAML and MDS patients when compared to de novo AML, but reached significance only for the duration of thrombocytopenia: 26 days versus 18 days (p less than 0.01). The complete remission (CR) rates were similar in primary AML: 67%, sAML: 62%, and MDS: 64%. The CR rates of patients younger than 45 years were 75% for de novo AML, 75% for sAML, and 71% for MDS. The number of hypoplastic deaths during remission-induction chemotherapy of patients with sAML and MDS was low. Four of the 36 patients treated for sAML or MDS died during subsequent hypoplastic phases induced by remission-induction chemotherapy. The remission duration without bone marrow transplantation (BMT) was significantly shorter (p less than 0.03) in MDS and sAML, when compared with primary AML. Longlasting complete remissions in MDS and sAML were only obtained in 3 of the 6 patients treated with allogeneic BMT. Intensive antileukemic therapy should be considered in young patients with MDS and life-threatening cytopenias or patients with sAML or RAEBt.

Adult↗