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Biomedical subjects

H L Haak

Publications and source records attributed to H L Haak.

At least 37 records · Page 2Linked to original sources
PubMed1993

Detection of monosomy 7 and trisomy 8 in myeloid neoplasia: a comparison of banding and fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) is a powerful tool for detection of numerical and structural chromosomal aberrations. We have compared conventional banding techniques and FISH for the detection of monosomy 7 (-7) and trisomy 8 (+8) in 89 patients with myeloid malignancies. Of these patients, 21 had -7, 30 had +8, four had both, and 34 had no aberrations or aberrations other than -7 or +8 as assessed by banding techniques. Sequential samples were available in 23 patients. Alphoid DNA probes specific for chromosomes no. 7 and 8 were used for FISH. As controls, 10 normal bone marrow (BM) samples were hybridized with the chromosomes no. 7 and 8 probes, and in addition all tumor samples were hybridized with a chromosome no. 1 specific probe. The cut-off value for -7 was 18% one-spot cells, and for +8 was 3% three-spot cells. FISH analysis of 44 samples with -7 or +8, and at least 10 metaphases evaluated, showed that the proportions of aberrant metaphase cells mirrored the interphase clone sizes. Most samples with nonclonal metaphase aberrations, including those with only a few metaphases, had increased numbers of aberrant interphase cells: 20% to 80% for -7, and 3% to 43% for +8. Interphase cytogenetics of the 34 samples without -7 or +8 did not show significant cell populations with -7 or +8. In four patients, -7 or +8 could not be confirmed by FISH due to additional structural aberrations, marker chromosomes, or wrongly interpreted banding results. As FISH will be used more and more in cytogenetic diagnosis, clinical follow-up, and therapy monitoring, it will be necessary to standardize FISH procedures and supplement the Standing Committee on Human Cytogenetic Nomenclature (ISCN) definitions of a clone with criteria specifically for in situ hybridization.

Acute Disease↗
PubMed1993

Myeloid but not lymphoid cells carry the 5q deletion: polymerase chain reaction analysis of loss of heterozygosity using mini-repeat sequences on highly purified cell fractions.

Interstitial deletions of the long arm of chromosome 5 are among the most characteristic abnormalities observed in myeloid disorders. To assess the lineage involvement of peripheral blood cells from patients with a 5q--anomaly, purified neutrophils, monocytes, T lymphocytes, and B lymphocytes were analyzed for loss of heterozygosity using six different highly polymorphic mininucleotide and dinucleotide (CA) repeat sequences from the 5q31 to 5q33 region. Ten patients were screened by polymerase chain reaction (PCR) amplification and proved to be informative for at least one marker. Six patients showed a complete or partial disappearance of an allele in myeloid cells, whereas cells of lymphoid lineages exhibited full heterozygosity. The other patients displayed no allelic loss, indicating that the informative markers were located outside the deleted chromosomal segments. In addition, three female patients who were also polymorphic for the BstXI site in the PGK-1 gene were analyzed for the methylation status of this gene. Clonality of hematopoiesis, as determined by non-random X-chromosome inactivation, followed the same cell pattern as the 5q-specific allelic losses. In conclusion, using tumor-specific and clonal markers, we have demonstrated that the 5q- anomaly is restricted to cells of myeloid origin, leaving lymphoid cells unaffected.

Adult↗
PubMed1993

Severe immunodeficiency in patients treated with fludarabine monophosphate.

Fludarabine monophosphate (FAMP) has been shown to be highly effective against low-grade malignant B-cell lymphoproliferative diseases. Because some opportunistic infections were observed in patients treated with FAMP, we investigated the influence of this drug on several parameters of immunocompetence. For 17 consecutive patients treated with FAMP for CLL or low-grade malignant lymphoma we studied T-cell subpopulations during and after therapy by flow cytometry and our findings were correlated with the clinical course of their disease. A pronounced decrease in the various T-cell subpopulations was seen in all cases, that for CD4+ cells was still present 11-13 months after the end of the therapy. In 7 patients a severe opportunistic infection developed; the outcome was fatal in 2 cases. Only 5 patients did not experience any serious infection. These results show that FAMP therapy in a dose of 25 mg/m2/day for 5 d every 4 weeks might be too toxic for patients with very advanced disease. However, in view of the efficacy of FAMP, the possibility of less intensive schedules for these advanced cases should be explored.

Adult↗
PubMed1993

Mitoxantrone, teniposide, chlorambucil and prednisone (MVLP) for relapsed non-Hodgkin's lymphoma. The impact of advanced age and performance status.

Fifty-seven patients with relapsed non-Hodgkin's lymphoma (NHL) of low, intermediate and high-grade malignancy were treated with mitoxantrone, teniposide (Vm26), chlorambucil (Leukeran) and prednisone (MVLP). The median age was 71 years; none of the patients was excluded due to poor performance status (PS). Out of 44 patients with PS (according to WHO) < or = 2, 38 responded with a median progression free survival (PFS) of 21.5 months. Of 13 patients with PS > 2, 6 responded with a median PFS of 8.2 months. Haematopoietic toxicity was related to PS rather than to dose intensity or bone marrow involvement. Three patients died within a short time due to toxicity; another two died later as a result of cardiac failure probably due to accumulated toxicity of adriamycin and mitoxantrone. MVLP chemotherapy is effective and feasible and has only moderate toxicity in patients with relapsed NHL and PS < or = 2, despite advanced age.

Adult↗
PubMed1992

Nonradioactive in situ hybridisation of the translocation t(1;7) in myeloid malignancies.

Bone marrow cells of four patients with t(1;7) and myelodysplasia or acute myeloid leukemia were analyzed using nonradioactive in situ hydridisation. As probes, centromeric alphoid DNA sequences of chromosomes 1 and 7, a satellite DNA probe for 1q12, and chromosome-specific libraries of chromosomes 1 and 7 were used. The breakpoints of the t(1;7)(p11;p11) as determined by banding analysis could be studied more accurately, and the recently proposed designation t(1;7)(cen;cen) was confirmed in all four cases. Colocalization of alphoid DNA sequences of chromosomes 1 and 7 by double target in situ hybridisation was demonstrated in metaphase cells and also in interphase nuclei. The in situ hybridisation method described is applicable for the screening of peripheral blood cells or archival material.

Acute Disease↗
PubMed1992

Hyaline-vascular type Castleman's disease with concomitant malignant B-cell lymphoma.

This case report describes a patient with localized hyaline-vascular (H-V) type Castleman's disease with concomitant malignant B-cell lymphoma. Malignant lymphoma has been described in association with multicentric type Castleman's disease, but not in association with the localized H-V type. Evidence for a relation between the two lesions in this patient by means of histologic, flow-cytometric, cytogenetic and gene rearrangement studies was not found.

Adult↗
PubMed1991

The effect of anticoagulants on the size of platelets in blood smears in the course of time.

In this study we measured platelet size in blood smears using the Kontron Mop Videoplan (Kontron Electronic Group, Weesp, Holland). The blood smears were prepared at different times after phlebotomy; samples were collected in three different anticoagulants and 100 consecutive platelets were measured in each smear. A number of platelet parameters were determined, some of which were based on the log normal distribution of the platelet area. We found that the size of platelets in blood smears is also dependent on the time after phlebotomy and the anticoagulant used. This may be important for the comparison of platelet areas, a characteristic of various disorders. Our data indicate that the optimal interval after phlebotomy for preparation of blood smears is 2-5 min.

Anticoagulants↗
PubMed1989

der(1)t(1;9): a specific chromosome abnormality in polycythemia vera? Cytogenetic and in situ hybridization studies.

Two patients with polycythemia vera and an extra der(1)t(1;9) chromosome are reported. In one patient this was found as the sole abnormality. The other patient originally presented with trisomy 9 but later developed an extra der(1) during the further course of the disease with disapperance of the extra chromosome 9. In situ hybridization studies on this latter patient proved that the centromere of chromosome 1 was involved in the formation of the derivative chromosome.

Adult↗
PubMed1989

[Are hematologic reference values applicable to the healthy elderly?].

In the healthy elderly (65-90 years; 80 men, 75 women) the variability of haematological findings was examined and compared with the reference range. In the men, the ranges for haemoglobin valves (7.4-10.5 mmol/l) and erythrocyte counts (3.8-5.5 x 10(12)/l) proved to be lower than the reference intervals (8.5-10.9 mmol/l and 4.4-6.0 x 10(12)/l respectively). For the women no discrepancies were found. The question arises whether the reference limits for haemoglobin and erythrocytes should be lowered for elderly men.

Aged↗
PubMed1987

Utility of the FAB classification for myelodysplastic syndromes: investigation of prognostic factors in 237 cases.

The utility and prognostic significance of the FAB classification was studied in 237 patients with a myelodysplastic syndrome. No significant differences in actuarial survival and probability of transformation to acute leukaemia were found in patients with RA, AISA or CMML. The median survival time for the RA group was 50 months, for the AISA and CMML subclasses more than 60 months. The probability of transformation for the RA, AISA and CMML subgroups showed a linear trend with a probability of 25% for the RA, 16% for the AISA and of 18% for the CMML groups after a 5 year observation period. A uniformly poor prognosis was found for the RAEB and RAEB/t subgroups with median survival times of respectively 9 and 6 months. Chromosomal abnormalities were found in 68 out of 155 patients (44%). Patients with only normal metaphases or with abnormal metaphases together with karyotypic normal cells had a longer median survival time and a lower probability for transformation as compared to those with only abnormal metaphases. The most important factor in prognosis is the number of blast cells in blood and bone marrow. Age and sex, and certain quantitative and qualitative abnormalities in the peripheral blood appear of limited prognostic value for patients with RA, AISA and CMML. The longer life expectancy of 35 patients with CMML as compared to other series seems to be related to the percentage of blast cells at the time of diagnosis.

Adult↗
PubMed1986

Trisomy of chromosome 22 in acute myelomonocytic leukemia.

A patient with acute myelomonocytic leukemia type M4, with a trisomy 22 as the only chromosomal abnormality is reported. All six previously published cases with this anomaly had acute myeloid leukemia. The subtype was AMMoL in five patients, and the subtype of the sixth one was not indicated.

Aged↗
PubMed1986

Significance of in vitro cultures in myelodysplastic syndromes.

Bone marrow samples from 20 controls, 41 patients suffering from various types of myelodysplasia and 19 suffering from ANLL were investigated by in vitro cultures. The cultures were stimulated by various concentrations of leucocyte conditioned medium (LCM) and PHA-stimulated conditioned medium (PCM) and were examined after 7 and 14 d. We found that, in clinically stable MDS, growth patterns and dose-response to CM's were mostly within the normal range. With progressive blastic transformation, these features became abnormal with an increase in cluster growth. Clusters responding to a high dose of LCM, persisting after 14 d and enhanced by PCM may represent 'early' clonogenic cells. These clusters were found in progressive MDS with increased numbers of blast cells. Clusters formed by 'late' clonogenic cells were found in normal bone marrow and stable MDS. In ANLL the disturbance of proliferation and maturation seems to be much more pronounced than in progressive MDS with blastic transformation. We conclude that the interpretation of in vitro bone marrow culture data in terms of a disorderly arrangement of clonogenic cells in MDS and ANLL is facilitated by comparing different conditioned medium stimulations and by scoring after different time intervals.

Acute Disease↗
PubMed1985

Evidence of fibrinogen breakdown by leukocyte enzymes in a patient with acute promyelocytic leukemia.

On daunomycin treatment of a patient with promyelocytic leukemia, leukocyte elastase appeared in large amounts in the patient's blood. Also, the plasma fibrinogen was found to be partially degraded to early, X-like, fibrinogen degradation products. These early fibrinogen fragments were isolated and showed a low anticoagulant activity in a thrombin time test. Early fibrinogen degradation products, produced with leukocyte elastase in vitro, have a similar low anticoagulant activity. In contrast, plasmic degradation products inhibit clotting of fibrinogen to a large extent. Although alpha 2-antiplasmin and plasminogen levels were low, antithrombin III levels were not decreased. The low anticoagulant activity of the isolated fibrinogen fragments, the presence of elastase activity in the plasma--both immunological and amidolytic--and the normal levels of antithrombin III suggest that granulocytic enzymes, whose release was enhanced by the cytostatic treatment, were responsible for degradation of fibrinogen in this patient.

Antineoplastic Agents↗