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Biomedical subjects

A Ehrsam

Publications and source records attributed to A Ehrsam.

At least 19 recordsLinked to original sources

In vitro effects of recombinant hemopoietic growth factors on progenitor cells from patients with myelodysplastic syndromes.

The effects of four recombinant hemopoietic growth factors (HGF) and of the impure factor HTB9 on proliferation and maturation of marrow myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells were studied in 22 cases of myelodysplastic syndromes (MDS). In most cases, IL-3, GM-CSF and G-CSF increased significantly the number of myeloid colonies, the best combination being IL-3 + GM-CSF. A significant increase in the myeloid colony/cluster ratio was also noted, but cytological examination of colony cells showed little maturation. The analysis of myeloid colony surface markers with four monoclonal antibodies (to CD13, CD15, CD33 and CD34) showed minor modifications with an increase of CD13 and CD15 in about one third of cases when compared to control without HGF. Erythroid colonies were obtained in one case with erythropoietin alone, and in 19 cases with the addition of GM-CSF and/or IL-3. In short-term liquid cultures, IL-3, GM-CSF and G-CSF increased 3H-thymidine incorporation. We conclude that progenitor cells of most MDS are able to proliferate in the presence of HGF, with wide case-to-case variations. However, the pattern of growth remains abnormal when compared to normal marrow. Although the combination of IL-3 and GM-CSF is the most efficient, there is a large overlap in the stimulating effects of all factors studied.

Antigens, CD↗

Surface marker expression in adult acute myeloid leukaemia: correlations with initial characteristics, morphology and response to therapy.

The clinical significance of surface markers was investigated in 145 cases of acute myeloid (AML) or undifferentiated leukaemia (AUL), using a panel of six monoclonal antibodies directed to NHL-30.5 antigen (expressed on poorly differentiated myeloid cells), CD13, CD14, CD15, CD33 and CD34 antigens. Expression of CD14 was correlated with higher leucocyte count, higher serum lactate dehydrogenase level and presentation with extramedullary disease. There was no strict correlation with the French-American-British classification. However, the expression of CD14 was associated with monocytic subtypes. CD15 was mainly expressed in M2 and M3 subtypes, and NHL-30.5 and CD34 antigens in AUL and M1 leukaemias. All patients were treated with the same intensive induction treatment. Staining by three antibodies had a prognostic value. The complete remission (CR) rates were 38% (26/68) in NHL-30.5-positive versus 75% (62/77) in NHL-30.5-negative cases (P less than 10(-5), 50% (37/74) in CD34-positive versus 72% (51/71) in CD34-negative cases (P = 0.007) and 70% (77/110) in CD15-positive versus 31% (11/35) in CD15-negative cases (P less than 10(-4). Expression of NHL-30.5 and CD34 antigen was associated with shorter survival (P less than 10(-3) and P less than 10(-2) respectively), whereas survival was longer in CD15-positive cases (P less than 10(-3). In multivariate analysis, expression of NHL-30.5 antigen, absence of CD15, and high LDH level were associated with poor survival. CR duration was not influenced by any of the factors studied, including antigen expression. These results suggest that leukaemias with less differentiated phenotype have a lower response rate to induction treatment.

Acute Disease↗

Expression of immunological markers on leukemic cells before and after cryopreservation and thawing.

We have studied the effects of cryopreservation on the viability and on the expression of surface antigens of acute leukemia cells. Marrow samples were obtained at initial diagnosis from 89 patients with acute myeloid leukemia (AML), acute undifferentiated leukemia (AUL), and acute lymphoid leukemia (ALL). In AML, the mean viability was greater than 90% in the types M1, M4, and M5 of the French-American-British classification, 79% in M2, and 3% in M3 types. The viability was 74% in AUL. In ALL, the viability was 95% for pre-B leukemias, but only 2% in T-cell leukemias. The expression of myeloid antigens was studied before and after freezing and thawing using three monoclonal antibodies (NHL30.5, against poorly differentiated granulocytic leukemias, VIMC6 against differentiated granulocytic leukemias and granulocytes; and UCHM1 or CRIS-6, against monocytic leukemias and monocytes). The percentage of cells stained by NHL30.5 and UCHM1 or CRIS-6 was very similar before and after cryopreservation. For VIMC6, the mean staining after cryopreservation was 60% of the initial one. In pre-B ALL, the stainings by anti common ALL antigen before and after cryopreservation were also very similar. We conclude that leukemic cryopreserved cells are suitable for immunologic studies. The recovery is, however, very low in promyelocytic AML and T-cell ALL.

Acute Disease↗

Expression of CD 19 antigen on acute monoblastic leukemia cells at diagnosis and after TPA-induced differentiation.

We have previously shown that CD 19, a B-lymphoid differentiation antigen, is expressed on acute myeloid leukemia cells. In this study, the expression of CD 19 and CD 14 (a monocytic antigen) was investigated in 18 cases of acute monoblastic leukemia. The staining by anti-CD 19 antibody (SB4) ranged between 26 and 81% of the cells, and was significantly correlated with the staining by anti-CD 14. Double stainings confirmed that the antigens were expressed on the same cells. After a 48-hr culture in the presence of TPA, most cells became adherent and lost CD 19 antigen, whereas CD 14 was still expressed with only minimal changes. It is concluded that CD 19 antigen is expressed on more immature stages of monoblastic leukemias. The hypothesis that CD 19 could be an early monocytic differentiation antigen is discussed.

Antigens, CD19↗

Acute leukaemia following high-dose chemoradiotherapy with bone marrow rescue for ovarian teratoma.

A case of acute leukaemia following intensive chemo- and radiotherapy for solid tumour is reported. A 15-year-old girl received four courses of chemotherapy with adriamycin, cyclophosphamide and cisplatinum after the surgical diagnosis of ovarian immature teratoma. An intensification treatment was performed with cyclophosphamide and total body irradiation, followed by marrow rescue. The diagnosis of myelomonocytic acute leukaemia was performed 8 months later. The patient died after a transient improvement following a treatment by hydroxyurea. The roles of the primary tumour, of the chemotherapy and of the marrow transplantation in the occurrence of leukaemia are discussed.

Acute Disease↗

Persistence of t(4;11) in cytologically normal bone marrow treated ex vivo with Asta-Z.

The chromosomal anomaly t(4;11) is closely related to a specific type of acute leukemia: occurrence in young children, hyperleukocytosis with a particular immunologic phenotype, and poor response to therapy. Allogeneic bone marrow (BM) transplantation has been done in a few cases. We report a case in which a complete remission was obtained after intensive therapy. Because no donor was available, an autologous BM transplantation was performed after purge ex vivo of the BM collection by Asta-Z. Relapse occurred at day 45.

Bone Marrow↗

Massive BACT chemotherapy with autologous bone marrow transplantation in 17 cases of non-Hodgkin's malignant lymphoma with a very bad prognosis.

A group of 12 children and 5 adults, all with diffuse non-Hodgkin's malignant lymphoma (NHML), received massive chemotherapy regimens. The stages of the disease were as follows: 7 patients were in second complete remission; 6 in a progressive phase of the disease; and 4 in first complete remission which occurred late in the course of the disease. All patients received BACT (BCNU+aracytine+cyclophosphamide+thioguanine) or TACC (idem with CCNU) at different dose levels: 6/17 received 10 Gy total-body irradiation (TBI) after BACT treatment; 16/17 received autologous bone marrow transplantation (ABMT) previously stored in liquid nitrogen to combat the medullary effects of chemotherapy. Direct therapy-related deaths occurred in 4/17 patients (1 Aspergillus endocarditis; 1 Moskowitz syndrome; 1 veno-occlusive disease of the liver; and 1 Escherichia coli pneumopathy) and 6/17 patients relapsed between days 25 and 70 of treatment. Seven out of these 17 patients are still alive NED 102-900 days (mean, 475 days) after the beginning of therapy without receiving maintenance treatment. Massive chemotherapy could thus be the best treatment for NHML in relapse, but the high percentage of early therapy-related deaths is a strong limiting factor for patients before relapse.

Adolescent↗

Skin preservation by programmed freezing.

There are several occasions when it may be useful to preserve skin grafts for at least 15 days, in a good enough state to provide viable autografts. We describe a technique of cryopreservation which facilitates this type of procedure. Stretched sheets of skin are incubated in a protective medium. Freezing is programmed with cooling rates of 1 degree/min first to 50 degrees C and 5 degrees/min thereafter. The skin is placed in bags that are stored in liquid nitrogen and when required for use is rapidly thawed. Thin and ultra-thin sections of this preserved skin were studied by light and electron microscopy. Cultures wer made from thawed skin and growing cells were found to contain epithelial-like or fibroblast-like elements. When pieces of thawed skin were replaced on their original donor site the autograft was successful. The technique we have described gave consistently good results and its clinical applications need further development and study.

Cryoprotective Agents↗

Continuous pH-measurement on anesthetized patients.

43 patients under general anesthesia were monitored by continuous tissue pH measurement and intermittent micro-blood-samples. The values obtained for the capillary pH and tissue pH were correlated. A highly significant correlation was found between tissular pH and capillary pH. Different methods of general anesthesia apparently do not influence the continuous tissue pH measurement.

Anesthesia, General↗

Continuous tissue pH measurement on the fetus during delivery.

Tissue pH values of 70 fetuses have been measured continuously during labor using the micro-electrode designed by Stamm. Significant correlation between continuous tissue pH and corresponding micro blood values can be shown. However, the relationship between patterns of tissue pH and capillary pH values seems not to be very constant. Therefore, the reliability of individual tissue pH measurements is still questionable.

Capillaries↗

[Preparation of leukocyte-free blood by a method of sedimentation-filtration].

After centrifugation of 450 ml-CPD-whole blood, 125 ml of packed red cells are diluted to 50 percent with saline (pH 7, 2). To remove leukocytes the diluted blood is filtered at room temperature through a newly devised column packed with cotton wool disks. 200 ml of red blood cells suspension are recovered and contain less than 5.10(6) leukocytes. Appropriate controls show that: 1. The filtered blood contains no pyrogen; 2. The red blood cells have a normal osmotic resistance; 3. The suspension can be maintained at 4 degrees C up to 5 days before transfusion without cellular damage.

Blood Sedimentation↗