Morphological Survey of Placenta in Trombophilia Related Hypoperfusion of Maternal-Fetal Blood Flow.

Complex and modern obstetric medical care provides a constant improvement for the pregnancy prognosis. Thus, young women with an undiagnosed pathology become pregnant and, during pregnancy, the previously undiagnosed pathology, without any clinical signs and symptoms, becomes present during pregnancy, having an unfavorable impact on the fetus and the health state of the pregnant woman. The gestational syndromes during pregnancy influence the woman's health state over a long period of time and the quality of the conception product. The recommendation, performance of laboratory tests and imagistic investigations at the right time during pregnancy, as well as a correct interpretation of their results, may prevent the onset of catastrophic occurrences including fetal death in utero and/ or maternal death. We report the case of a 30-year old primigesta, primipara (IGIP) patient with a singleton, naturally obtained pregnancy, severe preeclampsia, severe IUGR and thrombophilia.

Serologic diagnosis in the differentiation of autoimmune hemolytic anemias.

A complex serologic study was carried out in 20 patients with autoimmune hemolytic anemias (AIHA). The methods used were: the direct Coombs' test with specific sera anti IgG, IgM, IgA and complement (C), the direct and indirect test with papain treated erythrocytes (at 37 degrees C), determination of cold agglutinin titer and of warm and cold hemolysins. By these investigations using indigenous sera, the 20 cases of autoimmune hemolytic anemia could be classified: a) according to the thermal behaviour of autoantibodies, into warm antibody AIHA -- 15 cases, cold antibody AIHA -- 2 cases and both warm and cold antibody AIHA -- 3 cases; and b) according to the sensitizing globulin, into: IgG type -- 10 cases, IgG + C type -- 7 cases, IgG + IgM + C type -- 1 case, type C + cold agglutinins -- 2 cases.

Present-day problems of diagnosis and treatment in the idiopathic thrombocytopenic purpura.

A review is made of the data in the literature and of the authors' experience regarding the etiology and pathogenesis, diagnosis and therapy of the chronic form of idiopathic thrombocytopenic purpura (ITP). The mechanisms of production (after McMillan et al.) are presented schematically and the five criteria of ITP diagnosis suggested by Karpatkin are discussed: 1) decreased blood platelet count with direct or indirect signs of thrombocytolysis; 2) increased number of megakaryocytes in the bone marrow and/or signs of intramedullary thrombocytolysis; 3) direct or indirect signs of antiplatelet autoantibody presence in the plasma; 4) exclusion of a primary disorder and 5) absence of splenomegaly. The results of corticotherapy, splenectomy, platelet transfusion and immunosuppression (including "target" immunosuppressive therapy) in 188 patients with ITP, admitted to the clinic of Hematology--Bucharest between 1966 and 1978, are presented and analysed.

Bone marrow patterns in chronic lymphocytic leukaemia related to various clinical and haematological findings. A preliminary report.

In a retrospective study of 55 CLL cases subjected to bone-marrow biopsy, the histological pattern of the bone-marrow was correlated to the clinical and haematological data. Instead of the four histological patterns described by Rozman et al., five patterns have been established. The clinical staging according to the Montserrat score, compared with the bone-marrow pattern, showed a good correlation, when maintenance or replacement of normal haematopoiesis was considered. The bone-marrow pattern with maintained haematopoiesis was predicting a favourable clinical correlation; those with replaced haematopoiesis corresponded to a poor prognosis. The correlation is a useful index of severity and prognosis of CLL.

The test of spontaneous rosettes with sheep erythrocytes in lymphocytoses.

The test of spontaneous rosettes with sheep erythrocytes was used to estimate the rosette forming lymphocytes (RFL) in the peripheral blood from normal subjects and from patients with various lymphocytoses. The test was performed in 65 patients with: chronic leukemia (CLL), lymphocytic lymphosarcoma, Waldenström's macroglobulinemia, infectious mononucleosis, pulmonary tuberculosis, hyperthyroidism and pertussis as well as in 25 normal controls. The percentage of RFL was constantly and significantly low in all the cases of CLL. However, in absolute values the RFL count was found within normal limits or increased. Trying to establish a correlation between the number of T lymphocytes and the clinical forms of disease (aggressive and non-aggressive) on the one hand, and on the other hand to find the effect of cytostatic therapy, on this lymphocytic population, we observed that in the aggressive form the absolute values of RFL were obviously increased as compared with the other form and that cytostatic therapy reduced the number of RFL. The cellular immune deficit in CLL is discussed as well as the clinical utility of the rosette test with sheep erythrocytes for the estimation of the immune status in patients with malignant or reactive lymphoproliferations.

Studies on two biological phenomena in in vitro cell cultures: the reversibility of leukemic blast cells and the immunologic enhancement of tumor growth.

The nature of the leukemic process is discussed with respect to the possible in vitro transformation of the leukemic blast cells into myeloid differentiated cells. During the period 1968-1970 we noticed this process in bone marrow cultures in fluid medium. The differentiation was established on morphologic and cytochemical criteria; the proportion of mature cells or those undergoing maturation with peroxidase positive reaction increased over 50% reaching even 70-80%. Our recent observations can be discussed from several points of view but leukemic blast cell reversibility is now a phenomenon with therapeutical applications. The phenomenon of malignant cells growth enhancement has been considered as an antibody mediated immune process. In a previous paper we have demonstrated in AKR mice the possibility of achieving the growth enhancement of lymphoblastic cells in mixed cultures with normal autologous or isologous splenic cells. Other investigations have been carried out by means of mixed cultures in human leukemias and malignant lymphomas. The intensity of blast-cell proliferation was followed up by comparing the number of colonies and TH3 incorporation in simple cultures with those in mixed cultures. The observations made in the 20 culture systems followed-up over 3-5 and 8-10 days proved the "malignant cell growth enhancement" by the immune mononuclear cells (lymphocytes and macrophages).

The test of spontaneous rosettes with sheep erythrocytes in lymphocytoses.

The test of spontaneous rosettes with sheep erythrocytes was used to estimate the rosette forming lymphocytes (RFL) in the peripheral blood from normal subjects and from patients with various lymphocytoses. The test was performed in 65 patients with : chronic leukemia (CLL), lymphocytic lymphosarcoma, Waldenström's macroglobulinemia, infectious mononucleosis, pulmonary tuberculosis, hyperthyroidism and pertussis as well as in 25 normal controls. The percentage of RFL was constantly and significantly low in all the cases of CLL. However, in absolute values the RFL count was found within normal limits or increased. Trying to establish a correlation between the number of T lymphocytes and the clinical forms of disease (aggressive and non-aggressive) on the one hand, and on the other hand to find the effect of cytostatic therapy, on this lymphocytic population, we observed that in the aggressive form the absolute values of RFL were obviously increased as compared with the other form and that cytostatic therapy reduced the number of RFL. The cellular immune deficit in CLL is discussed as well as the clinical utility of the rosette test with sheep erythrocytes for the estimation of the immune status in patients with malignant or reactive lymphoprpliferations.

Epstein-Barr virus (EBV). VI. Incidence of EBV antibodies in patients with malignant lymphoproliferative diseases.

Serum samples from 52 patients with malignant lymphoproliferative diseases and 12 clinically healthy subjects were tested by indirect immunofluorescence (IF) reaction for the presence of specific EB antibodies anti-VCA and active EBV infection. The tests revealed EB antibodies anti-VCA in 32 patients with lymphoproliferative diseases and in 2 clinically healthy subjects and active EBV infection in 18/32 and in 0/2 EB anti-VCA positive patients and clinically healthy subjects, respectively.

Polycythemic blood perfusions in severe aplastic anemia.

The course of two cases of severe aplastic anemia (AA) was followed up in two young male patients who, besides the conventional therapy, received perfusions with blood obtained from patients with polycythemia vera (PV). Case 1 received 4 units of PV blood from a unique donor. During the following week an obvious clinical relief, as well as increase of the peripheral blood values were recorded. Subsequently, the bone marrow was progressively repopulated with normal precursors and the peripheral blood picture reverted to normal. In case 2, 9 units of PV blood, obtained from two donors, were administered. During the next week a transient clinical and hematological improvement was obtained, but later on the progressive granulocytopenia and the infections led to exitus through a toxic-septic shock. It is assumed that PV blood may be a good replacing and a possible stimulatory therapeutic material, useful to overcome the early critical stage of severe AA.

Comparative cytogenetic and cytologic study in malignant lymphomas.

The possibility of a cytogenetic-cytologic correlation with implications in the diagnosis, evolutivity and prognosis of malignant lymphomas was studied. Cytogenetic investigations were carried out comparatively in the lymph node and spleen lymphoid cells from 25 patients with malignant lymphomas and in normal subjects or patients with malignant tumors. The dominant malignant cellular type was found to correspond genotypically to the abnormal clone. In lymphomas with more differentiated cells the chormosomal abnormalities were limited to a single chromosomal group, while in those with less differentiated cells there were many clonal chromozomal abnormalities. The pathogenic significance of an extra-chromosome in the C-group (observed in most of the cases) is discussed.

Hypotheses on the role of chromosomal changes in leukemias. Application of the Weibull distribution function.

Investigations were carried out in 38 patients with acute leukemias or with chronic myeloid leukemias in the blast phase and a correlation was made between the cytogenetic aspect and the survival time. The interpretation of results was made by the Weibull distribution function. It was mathematically demonstrated that in the leukemic patients with chromosomal aberrations there is a preclinical period of over 40 months necessary for the formation of these anomalies. Chromosomal aberrations, the absence of mitoses and age over 70 proved to be aggravating factors in the diseases investigated.

A case of erythrophagocytic T4 lymphoma. Immunological and morphological peculiarities.

One case of T-cell lymphoma with atypical malignant cells is reported. Some of the clinical features, morphological characteristics and functional activity (erythrophagocytosis) of malignant cells suggested malignant histiocytosis. The malignant disease started with splenomegaly and developed with hepatomegaly, bone marrow infiltration, discrete lymphadenopathy and leukaemic picture. Proliferated cells were characterized by ambiguity. In addition to phagocytic capability, presence of complement receptors and ultrastructural features proper to the macrophagic lineage, the cells expressed T-cell determinants (E receptors, T3, T4 and T11 antigens) and were peroxidase and esterase-negative. Erythrocytes were partially or completely dehaemoglobinized and presented the phenomenon of autolysis in different stages of development. Because this lymphoma is difficult to diagnose and apparently resistant to therapy, its recognition and further study are warranted.

Acute promyelocytic leukemia with T-cell markers and particular response to treatment. Report of a case.

A case of acute leukemia with atypical malignant cells is reported. The clinical picture and coagulation studies were consistent with a disseminated intravascular coagulation syndrome. Morphologically, the leukemic cells from the peripheral blood and bone marrow showed azurophilic granules. More than 80% of cells were hypergranulated, resembling the macrogranular type of promyelocytes. Ultrastructural studies and the pattern of endogenous peroxidase were consistent with the microgranular type of promyelocytes in about 20% of the leukemic cells. Auer bodies were present in both types of atypical promyelocytes. Cytochemically, the whole malignant population exhibited intense peroxidase activity. Studies with monoclonal antibodies showed that about 45% of the proliferating cells expressed T-cell markers T3, T4, T8 and T11, but the cells were not reactive with OKM1 monoclonal antibodies. The chemotherapy for acute promyelocytic leukemia was inefficient, and the prompt disappearance of the blood abnormalities was observed only when chemotherapy for acute lymphoblastic leukemia was started. Therefore, it seems that in some cases of leukemia with hybrid types of malignant cells the morphological features determine the clinical picture, while the patient's response to the therapy is conditioned mainly by the cell surface phenotype.

The role of spleen in the pathogeny of aplastic anemia related to increased number of CD3+ CD8+ FcR+ cells.

The role of spleen in the pathogeny of aplastic anemia (A.A.) related to excessive suppression, and the value of splenectomy in the treatment of this disorder is still debated and unclear. In an attempt to find out why some patients respond to surgery and others do not, an immunologic study was carried out in 16 patients with aplastic anemia. Lymphocytes surface markers CD3, CD4, CD8, HLA-DR, Fc receptors (FcR) and CD4/CD8 ratio were determined before and after splenectomy in the patients' peripheral blood, and in the spleen. In addition, the number of granulo-monocytic colony forming cells (GM-CFC) before and after splenectomy was estimated. Nine of the cases showed increased CD3+ CD8+ FcR+ cells, reversed CD4/CD8 ratios (both, in peripheral blood and in spleen), and a low number of GM-CFC. In all these cases, splenectomy induced an improvement of the clinical, hematological, and immunological parameters, thus suggesting that spleen represents an important "reservoir" for CD3+ CD8+ FcR+ cells, which seem to exert a suppressor effect on the hematopoietic progenitors. In splenectomized patients who did not respond to surgery, the pathogenic mechanism was probably related to defective help (3 cases with low values of CD4+ cells), to defective suppression (2 cases with decreased number of CD8+ cells), to a stem cell defect or a deficiency in the stem cell microenvironment (2 cases with normal helper/suppressor ratio). These observations support the conclusion that splenectomy is indicated and may be successful only when the phenotypic markers show an increased number of CD3+ CD8+ FcR+ cells.

Changes of the cellular immunity tests during the evolution of Hodgkin's disease.

To detect the changes of cellular immunity which occur at the same time as the pathological process and to find out the possible biologic indicators with prognostic value, a study was carried out on 140 patients with Hodgkin's disease (HD) in different clinical periods: onset, under therapy (cytostatics and/or irradiations), remission, after splenectomy and under immunotherapy. The study of cellular immunity included the determination of lymphocytes subpopulations by the rosette tests and their functional estimation by tests of blastic transformation to mitogens and antigens. Though the values obtained presented a wide dispersion, the rosette tests showed variations in correlation with the clinical stage, therefore with the severity of disease. It was observed that therapy and splenectomy change the cellular immunity tests. The only test with a certain prognostic value was found to be the in vitro lymphocyte response to PPD which became positive after therapy, particularly in the group of patients who showed good response to treatment. A dynamic follow-up of the cellular immunity tests might give an indication on the mechanisms of production of the immune deficit in HD.

LAP negative and Ph1-positive hemorrhagic thrombocythemia.

Cytochemical and cytogenetic studies were carried out in 4 patients with chronic myeloproliferative disorders. These corresponded only partially to the clinical and hematologic criteria for the diagnosis of hemorrhagic thrombocythemia (HT), yet with a low leukocyte alkaline phosphatase (LAP) level and in the presence of the Ph1 positive 46, XX, mitoses. The authors discuss the significance of the presence of the Ph1 chromosome as well as the possibility of transition forms among chronic myeloproliferative disorders.

Hairy cell leukemia. Immunological study.

The study has been performed on peripheral blood and splenic malignant cells from 16 patients with hairy cell leukaemia (HCL). The cell surface markers were identified by rosette techniques and using monoclonal antibodies (m Ab). The surface markers' expression of the hairy cells (HC) varied. The E receptors, the T-cell antigens, the HLA-DR antigens and smIgG were either expressed or not according to the affected organ, the progress of illness, or the treatment. The surface pattern changed sometimes in the same patient during the progress of illness. These observations demonstrate that HCL is a unique disease with malignant cells characterized by a marked variability of the cell surface markers. To demonstrate the ability of hairy cells to bind labile smIgG, the cells were studied by affinity chromatography on SpA-Sepharose 6MB and by ES-rosette assay. The percent of cells bound on SpA-Sepharose varied between 6% and 66%, representing the hairy cells with labile-bound smIgG. With affinity chromatography it was also possible to separate the hairy cells with a special phenotype: T3+ T4+ T8+ T11+ surface membrane labile-bound IgG+ (11gG+) FcR+, HLA-DR+ EACD+ (Ripley rosette forming cells), resembling a normal subset of large granular lymphocytes (LGL). The percentage of these cells varied between 60% and 86% of the bound cells. These observations suggest that in HCL, the malignant transformation might involve a common progenitor for the B, T and LGL lineages, the hairy cell being a hybrid type of malignant cell. Its main immunological peculiarity is the marked mobility of the surface membrane structures and hence the lability (plasticity) of the surface markers' expression.

[Acute lymphoblastic Ph1-positive leukemia with a hybrid phenotype. The significance of the Ph1 anomaly and the hybrid phenotype]. / Leucemia acuta limfoblastica Ph1 pozitiva cu fenotip hibrid. Semnificatia anomalie Ph1 si a fenotipului hibrid.

The present paper reports on a case of acute lymphoblastic leukemia with t(9q+; 22q-) and surface markers specific of the B and T lymphoid line (hybrid phenotype). The fundamental (genotypical and phenotypical) and practical aspects (nosologic and therapeutical aspects) of this particular subtype of Ph1-positive acute leukemia and hybrid phenotype are discussed.

A particular case of large granular lymphocytes lymphoma.

A patient with non-cutaneous lymphocytic lymphoma with leukaemic spread is reported. The large majority of the peripheral blood mononuclear cells formed rosettes with sheep erythrocytes (E), had receptors for the Fc portion of IgG (Fc gamma R) and displayed an unusual enzymatic profile. Part of these cells had also labile bound surface membrane IgG. The leukaemic cells were morphologically characterized as large granular lymphocytes (LGL) and consisted of two different types of cells: lymphoid cells and monocytoid cells. The histopathological diagnosis was T-cell lymphoma, pleomorphic type, diffuse. Despite their morphological heterogeneity, all the proliferative cells had the same immunological phenotype, showed normal ADCC activity but no NK activity. After three months, without specific treatment, the surface pattern changed: the cells resembled mature LGL and the NK activity increased. The cytochemical study of the leukaemic cells revealed an enzymatical peculiarity: besides an enzymatic profile characteristic for relatively mature LGL, the cells also displayed peroxidase activity. This unusual aspect--the expression by an individual malignant cell of markers believed to be restricted to a single cellular lineage--might be interpreted as a lineage infidelity or lineage promiscuity. The observation that this lymphoma developed in a patient with a long history of hypogammaglobulinaemia is of particular interest.

Congenital dyserythropoietic anemia type II. Radioautographic, ultrastructural and cytogenetical study in two familial cases.

The case of two sisters is reported in whom morphological (multinucleated erythroblasts in the bone marrow) and serological (positive Ham test, negative sucrose and water-sugar tests) characteristics of a congenital dyserythropoietic anemia type II were found. Radioautographic, cytogenetic and electron microscope studies confirmed the presence of an inefficient erythropoiesis and of a membrane defect, common in this disease. The finding of a nil LAP score has never been reported so far.