PubMed Health⌕ Search

Biomedical subjects

M Freund

Publications and source records attributed to M Freund.

At least 163 records · Page 9Linked to original sources
PubMed1996

Fifty-one patients with acute myeloid leukemia and translocation t(8;21)(q22;q22): an additional deletion in 9q is an adverse prognostic factor.

The translocation t(8;21)(q22;q22) occurs in 6 to 12 percent of patients with AML, and usually predicts a good response to chemotherapy with a high remission rate and a relatively long median survival. The influence of additional chromosome aberrations on the clinical outcome of patients with t(8;21) is unclear. We analyzed 51 cases of acute myeloid leukemia carrying a translocation t(8;21)(q22;q22); 23 female and 28 male patients. The complete remission rate was 92 percent and median overall survival was 52.4 months. The median overall survival of female patients was significantly worse than of male patients (37.2 months vs not reached, P = 0.025). Additional chromosome aberrations were detected in 41 patients at diagnosis (80 percent), 31 (61 percent) had lost a sex chromosome, seven (14 percent) showed a partial deletion of the long arm of chromosome 9 and in three patients (6 percent) a gain of chromosome 8 was observed. Whereas the loss of a sex chromosome had no influence on prognosis, a partial deletion of the long arm of chromosome 9 was an unfavorable prognostic factor. The median overall survival of the seven patients with del(9q) was only 12.5 months and thus significantly shorter than in patients with only t(8;21) or with t(8;21) and additional sex chromosome loss (median survival not reached: P = 0.0010).

Acute Disease↗
PubMed1996

Species specific immunoassays to measure blood platelet and coagulation activation in the rat.

The purpose of this study was to develop specific and sensitive immunoassays to detect early indices of hypercoagulability in the rat. Rat platelet factor 4 (rPF4) and rat fibrinopeptide A (rFPA) assays, tools for the detection of activation of platelets and coagulation respectively, were designed using antibodies raised against purified rPF4 and against synthetic rFPA. The relevance of these new assays and of the commercially available ELISA kit for thrombin-antithrombin III (TAT) complexes was demonstrated in a rat model of a prethrombotic state induced by intravenous infusion of varying doses of thrombo-plastin (90 to 2400 microliters/kg/h). In this model, the immunoassays allowed simultaneous detection of low levels of rFPA and rPF4 which were correlated with fibrinogen and platelet consumption and TAT generation and further proved to be of higher sensitivity than the classical methods of platelet count or measurement of fibrinogen levels. Plasma concentrations of rFPA, rPF4 and TAT were dependent on infusion time and thromboplastin dose, while hirudin (1 mg/kg) prevented their appearance. Thus the new specific immunoassays for rPF4 and rFPA and the commercial human TAT assay represent useful tools for pathophysiological studies or the screening of antithrombotic drugs in rats.

Animals↗
PubMed1996

Long-term interleukin-3 and intensive immunosuppression in the treatment of aplastic anemia.

We have assessed in a phase I/II clinical study the tolerability and efficacy of long-term application of recombinant human interleukin-3 (rh-IL-3) in combination with antithymocyte globulin (ATG) and cyclosporin A (CSA) in 13 patients with aplastic anemia who were refractory to or relapsed after previous immunosuppressive treatment. Four cohorts of three patients were consecutively enrolled so that they received rh-IL-3 on days 9, 6, 3 and 1 after start of ATG/CSA treatment. Yeast-derived recombinant human IL-3 was administered by daily subcutaneous injection until day 90 at a dosage of 250 micrograms/m2. Long-term application of rh-IL-3 was well tolerated. The combination of rh-IL-3 with immunosuppression did not modify the known toxicities of ATG and CSA. Incidence and severity of rh-IL-3-related adverse events was less than in other phase I/II trials of rh-IL-3 as single-agent therapy. One might speculate that co-medication with CSA alleviates rh-IL-3-induced side effects. Three of eight patients with refractory AA and all four patients with relapsed AA responded to the combined treatment within four months. The median time to response was 91.5 days. There was evidence for an rh-IL-3-dependent response in two patients. Long-term rh-IL-3 did not cause stem cell exhaustion. One patient died early during the course of the study from EBV-driven lymphoproliferative disease. Two patients developed acute myeloid leukemia 4 and 22 months after cessation of rh-IL-3. In conclusion, long-term rh-IL-3 in combination with immunosuppression is well tolerated. The response rate to the combined treatment in refractory and relapsed AA was high. Recombinant human IL-3-dependent responses suggest efficacy. A prospective randomized trial comparing immunosuppression alone versus a combination with rh-IL-3 is warranted.

Adolescent↗
PubMed1995

Cytogenetic findings in 179 patients with myelodysplastic syndromes.

Cytogenetic analyses were performed on 266 bone marrow and peripheral blood samples from 179 patients with myelodysplastic syndromes (MDS). According to the FAB classification, 42 patients presented with RA, 18 with RARS, 37 with RAEB, 22 with CMML, and 29 with RAEB-T. Nine patients showed a secondary MDS (S MDS). FAB classification was not available for 22 patients. Clonal karyotype anomalies were found in 92 patients (51.4%). Complex chromosome abnormalities occurred in 17 (18.5%) of them. An evolution of the karyotype was detected in 16 cases (17.4%). Cytogenetically independent cells or cell clones were found in eight patients. Nonclonal chromosome abnormalities were uncovered in 29 (16.2%) of the 179 MDS patients. Consecutive studies were performed in 48 patients and revealed a good correlation of initial karyotype and clinical course. The most frequent single anomalies were 5q- in 29 (31.5%), -7 in 22 (23.9%), trisomy 1q in 14 (15.2%), and +8 in 13 (14.1%) of 92 patients respectively. Our cytogenetic findings are presented in detail and discussed in relation to patients' age, morphological classification, clinical course, and prognostic impact. The contribution of cytogenetic findings to the delineation of multistep pathogenesis of MDS with special emphasis to karyotype instability is demonstrated.

Adult↗
PubMed1995

Twenty-three cases of acute lymphoblastic leukemia with translocation t(4;11)(q21;q23): the implication of additional chromosomal aberrations.

The translocation t(4;11)(q21;q23) is one of the most common specific chromosomal aberrations in acute lymphoblastic leukemia (ALL), occurring in 2% of childhood and in 5-6% of adult cases. Especially in adults, the t(4;11) is associated with a poor prognosis. In order to determine the significance of clonal chromosome aberrations that occur in addition to t(4;11), we studied the karyotypes and clinical courses of 23 patients with acute lymphoblastic leukemia and a translocation t(4;11)(q21;q23). Additional clonal chromosome aberrations were found in ten patients. An isochromosome i(7)(q10) and a trisomy 6 were observed most frequently as secondary anomalies. Clonal evolution was detected in four of six patients analyzed at diagnosis as well as at relapse. With treatment carried out according to modern risk-adapted therapy protocols, no difference in outcome was observed between patients with clonal chromosome aberrations in addition to t(4;11) at diagnosis and those without.

Adolescent↗
PubMed1995

Establishment and characterization of a novel CD34-positive human myeloid leukemia cell line: MHH225 growing in serum-free culture.

A new human multilineage myeloid leukemia cell line, MHH225, has been established in our laboratory from the bone marrow of a 60-year-old patient suffering from acute megakaryoblastic leukemia (M7); it provides a unique model for studying the effect of biologic and chemical agents on the lineage specificity of a multipotent myeloid leukemia clone containing a mixed population of megakaryoblast, erythroblast, and myeloblast cells in a serum-free culture. Morphologically, all 225 cells are large blast cells with basophilic cytoplasm containing no granules, large round nucleus containing 2-3 prominent nucleoli, and fine chromatin structure and a large nuclear/cytoplasm ratio. The MHH225 cells are CD34+HLA-DR+CD33+CD13+ with 57.6%, 28.3%, and 7.8% of them being CD41+, glycophorin A+, and CD15+, respectively, and all lymphoid-specific antigens are negative. The karyotype analysis of MHH225 cells revealed a deletion of the short arm of chromosome 7: del(7)(p13)-, a whole-arm translocation between the long arms of chromosomes 9 and 21: t(9;21)(q10;q10), and a chromosome 11 with an elongated long arm due to duplication of chromosome 11 material as well as to translocation of part of chromosome 9 onto 11q+. Also, chromosome 21 was deleted in some metaphases or showed a ring formation in other metaphases. Utrastructurally, MHH25 cells display a strong platelet peroxidase activity in the nuclear envelope and the endoplasmic reticulum. The MHH25 cells have been grown exponentially without growth factors or conditioned media or serum only in RPMI1640 culture medium. None of the myelopoietic growth factors, i.e., interleukin-3, GM-CSF, G-CSF, erythropoietin, or interleukin-6, has any effect on the proliferation and differentiation of MHH25 cells. The two, hematopoietic inhibitory cytokines, interferon-alpha and tumor necrosis factor-alpha, have only minimal growth inhibitory effect. Stem cell factor showed only weak growth-stimulatory effect on MHH225 cells but significantly inhibited chemotherapy-induced apoptosis in these cells. The new cell line MHH225 should constitute a useful model for studying stem cell antigen (CD34)-positive human multilineage myeloid leukemia cells carrying a deletion in the short arm of chromosome 7 and an aberration in chromosome 11 and provide a unique tool for investigating human hematopoietic stem cell biology and its cytokine regulation in serum-free cultures. To our knowledge, the MHH225 cell line is the first human CD34-positive leukemia cell line growing in serum-free cultures to be established.

Antigens, CD34↗
PubMed1995

High-dose cytosine arabinoside and daunorubicin postremission therapy in adults with de novo acute myeloid leukemia. Long-term follow-up of a prospective multicenter trial.

A total of 149 consecutive de novo AML patients aged 50 years or less (median age = 37 years) were enrolled in this prospective multicenter trial initiated in May 1985. All patients received the same induction and early consolidation therapy with daunorubicin (DNR), cytosine arabinoside (Ara-C), and etoposide (DAV). High-dose Ara-C/DNR therapy included Ara-C at 3 g/m2, in 12 doses (HD-Ara-C/DNR I) and eight doses (HD-Ara-C/DNR II), followed by DNR 30 mg/m2 for 3 days. A complete remission (CR) was achieved in 104 (70%) patients; 61 complete responders received at least one cycle with HD-Ara-C/DNR. If those patients who were transplanted in first CR (n = 26), were not considered, the median relapse-free-survival (MRFS) of the remaining 78 patients was 15 months, with a probability of relapse-free survival (RFS) at 116 months of 30% (95% CI, 20-40%) after a median follow-up of 95 months. The MRFS of the HD-Ara-C/DNR consolidated patients was 25 months, with a probability of RFS at 116 months of 37% (95% CI, 24-50%). If all patients who were transplanted (n = 44) were not considered, the median survival time (MST) was 18 months with a probability of being alive at 118 months of 24% (95% CI, 16-33%). MST of the HD-Ara-C/DNR consolidated patients was 58 months with a survival probability of 46% (95% CI, 31-60%) at 118 months. Prognostic factor analysis did not reveal any significant influence of age, sex, FAB subtype, white blood cell count, hemoglobin level, thrombocyte count, LDH, or response to the first induction course on RFS of the HD-Ara-C/DNR consolidated patients. In summary, HD-Ara-C/DNR consolidation can improve the long-term outcome of a subgroup of de novo AML patients. Further improvement of the outcome seems to depend on the identification of patients with an inferior outcome under that strategy who might benefit from alternative treatment strategies.

Adolescent↗
PubMed1995

Fetal lung maturation in congenital diaphragmatic hernia.

OBJECTIVE: Our purpose was to determine whether congenital diaphragmatic hernia is associated with abnormalities of fetal lung maturation. STUDY DESIGN: We measured surfactant protein A and saturated phosphatidylcholine in amniotic fluid from 19 pregnancies with a prenatal diagnosis of congenital diaphragmatic hernia (gestational age 16 to 40 weeks) and 48 control pregnancies (gestational age 16 to 39 weeks). Results were compared by analysis of covariance. RESULTS: Beyond 34 weeks of gestation there was a progressive rise in amniotic fluid surfactant protein A and saturated phosphatidylcholine in control pregnancies, whereas in most fetuses with prenatal diagnosis of congenital diaphragmatic hernia these values remained low (p < 0.01). Amniotic fluid surfactant protein A was lower in fetuses with congenital diaphragmatic hernia who died or required extracorporeal membrane oxygenation than in survivors treated with conventional management (4.9 +/- 2.9 vs 16.8 +/- 5.7 micrograms/ml surfactant protein A, respectively, p < 0.05 by Mann-Whitney U test). CONCLUSIONS: There are decreased surfactant components in amniotic fluid in many pregnancies complicated by congenital diaphragmatic hernia, which may reflect fetal lung immaturity or hypoplasia.

Amniocentesis↗
PubMed1995

Characteristic biological features of human megakaryoblastic leukaemia cell lines.

Both normal and leukaemic human megakaryocytopoiesis are stimulated by several cytokines, including stem cell factor, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-3, GM-CSF/interleukin-3 fusion protein, interleukin-6, interleukin-11, basic fibroblast growth factor and thrombopoietin, but are inhibited by tumour necrosis factor-alpha, platelet factor 4, beta-thromboglobulin, thrombin, interleukin-4, interferon-alpha and interferon-gamma. Human megakaryoblastic leukaemia cell lines have common biological features, including high expression of the megakaryocytic specific antigen: CD41; high expression of the early myeloid antigens: CD34 and CD33; constitutive expression of interleukin-6 and platelet-derived growth factor; complex karyotype picture; expression of c-kit: the stem cell factor receptor; growth-dependency or -stimulation by stem cell factor, interleukin-3 and/or GM-CSF; megakaryoblastic differentiation by phorbol-myristate-acetate; and in vivo tumorigenicity in mice is associated with marked fibrosis. Only a few agents including phorbol-myristate-acetate; vitamin D3, interferon-alpha, interferon-beta 2, erythropoietin and thrombin have been reported to induce megakaryocytic differentiation in the human megakaryoblastic leukaemia cells.

Adult↗
PubMed1995

Magnetic resonance angiography in 140 neuropediatric patients.

Three-dimensional magnetic resonance angiography (MRA) is a noninvasive technique that images the intracranial arterial vasculature without contrast agents. The suitability of MRA was evaluated for routine use and all children were prospectively studied with conventional MR imaging and time off flight MRA (FISP3D). All MR studies were performed on a 1.5 T-MRA system using a circularly polarized head coil. The study comprised 140 children, ages 3 weeks to 18 years, with different neuropediatric diseases. Major cervical and intracranial arteries were visualized in all age groups. Smaller branches of the supratentorial arteries were identified inconstantly and the number of arteries visualized increased up to the age of 6 years. Sixty-seven children (47%) had normal intracranial vasculature. MRA demonstrated anatomic variations in 21 patients (15%). Twenty-two of 32 children with congenital malformations demonstrated abnormalities of the intracranial vasculature. The diagnostic value of MRA was confirmed in 11 of 12 patients after neonatal stroke and in 3 of 10 children after stroke at older ages. Seven of 18 children with acute hemorrhage demonstrated arteriovenous malformations or an aneurysm on MRA. The correlation with digital subtraction angiographic findings was established in 13 patients. In 9 of 13 children with brain tumor, MRA proved to be diagnostically valuable. MRA proved to be of particular value in the evaluation of the carotid artery following extracorporeal membrane oxygenation therapy. MRA can be used in children of all age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

[Double spiral CT angiography].

AIM: To evaluate the clinical value of CT angiography using double-spiral CT technique. METHOD: 7 patients with peripheral occlusive disease were examined after stent placement into iliac arteries (5/7) or prior surgery under the clinical suspicion of an occluded vascular graft (2/2). After a delay of 25 sec two spiral CT-scans, each of 32 sec duration, were started. The average interscan delay was between 12-15 sec. The total examination time was about 100 sec and the total range 36 cm using a slice thickness of 3 mm and a table feed of 6 mm/sec. 150 ml of contrast material were injected continuously with 3 ml/sec. RESULTS: All stents were exactly located and diagnosed as patent (6/6) in comparison to intraarterial angiography. Two occluded vascular grafts were diagnosed, confirmed by surgical findings (2/2). Density measurements showed enough of contrast material in the vessels to perform CT-angiography even in the second part of the examination. CONCLUSION: Double-spiral CT angiography is a clinical applicable and helpful method to examine patients with peripheral occlusive disease. It allows to double the examination range without losing the advantages of small slice thickness.

Aged↗
PubMed1995

[Spiral CT angiography after the application of an iliac artery stent].

PURPOSE: To evaluate the diagnostic and clinical value of CT-A performing MIP- and SSD-reformations after intraarterial iliac stent application. METHODS: In a prospective study 32 patients underwent CT-A after stent placement in the iliac arteries. The vascular morphology was analyzed regarding neointimal hyperplasia and calcification pattern. The results were compared with those of clinical findings (walking distance), Doppler ultrasound (ankle-brachial index) and DSA. RESULTS: All 47 stents were visible and patent (100%). One misplacement was identified. A good correlation was found between an improved ankle-brachial index and CT-A (88.5%) and extension of the walking distance and CT-A (92.3%). Concerning location, number and grade of stenoses the results between CT-A and DSA matched in 42.1%. An exact mapping of calcified plaques was possible in all cases. CONCLUSIONS: CT-A as MIP is shown to be superior than DSA with regard to calcifications. Complementary to the indirect methods of the ankle-brachial index and walking distance, CT-A is useful for therapy control after vascular stent placement.

Aged↗
PubMed1995

Cross-reactivity of human molecular markers for detection of prethrombotic states in various animal species.

The aim of the present study was to investigate the reactivity of immunoreagents developed for clinical applications in humans in different animal species (hen, mouse, rat, rabbit, guinea-pig, dog, pig, sheep, baboon). Prothrombin fragment 1 + 2, thrombin-antithrombin III complex and fibrinopeptide A were tested for coagulation, platelet factor 4 and beta-thromboglobulin for platelet activation, glycoprotein IIb-IIIa, glycoprotein Ib and P-selectin for platelet membrane glycoproteins, D-dimers for fibrinolysis, thrombomodulin for activation of endothelial cells and thrombospondin and von Willebrand factor for adhesive proteins. Prothrombin fragment 1 + 2, platelet factor 4, beta-thromboglobulin and D-dimers were revealed only in baboons. Fibrinopeptide A was well detected in baboons but weakly in mice, dogs, pigs and sheep. Whereas glycoprotein IIb-IIIa was revealed on guinea-pig, dog and sheep platelets and glycoprotein Ib on rabbit and dog platelets, P-selectin and thrombomodulin were never detected. Thrombospondin was revealed in hens, mice, rats, guinea-pigs, pigs, sheep and baboons and von Willebrand factor in mice, rats, guinea-pigs, dogs, pigs, sheep and baboons. Interestingly, thrombin-antithrombin III complex (TAT) was detected in all species tested except the hen. A time- and dose-dependent increase in TAT was observed when rats, dogs or pigs were infused with thromboplastin (4.5-450 microliters/kg/h), while administration of hirudin (1 mg/kg) abolished this TAT generation. Thus, the TAT immunoassay could provide a tool for the screening of antithrombotic drugs in a number of animal species. However, the possibility of using a wider panel of human immunoreagents would appear to be restricted to baboons which display good species cross-reactivity.

Animals↗
PubMed1995

Neonatal stroke involving the middle cerebral artery in term infants: clinical presentation, EEG and imaging studies, and outcome.

Six children with neonatal cerebral infarction of the middle cerebral artery are reported. Seizures or respiratory distress were the initial symptoms. In some cases abnormal findings appeared earlier on EEG than on ultrasound. The EEG changes were concordant with the localization of the lesion. Ultrasound examinations revealed an echodense structure within the vascular territory, after a phase of appearing to be normal, highly suggestive of cerebral infarction. The diagnosis was confirmed by CT scan. Findings on EEG, cranial ultrasound and CT suggested that the stroke represented a late intra-uterine event. At long-term follow-up, six children had failed to develop normally for age and had become obviously hemiplegic as gross motor development proceeded. Four of the patients had developed epilepsy. These data indicate that the outcome of neonatal stroke may not be as positive as previously reported.

Brain↗