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Biomedical subjects

P Reizenstein

Publications and source records attributed to P Reizenstein.

At least 127 records · Page 7Linked to original sources

Immune phenotype heterogeneity in AML.

Blood cells from 46 patients with acute myeloid leukaemia were studied for expression of various surface markers, defined by a panel of 12 monoclonal antibodies and the expression of Fc gamma receptors. Corresponding studies were done on normal bone marrow cells. Antibodies which bound to leukaemic cells in high frequencies were those which most frequently also bound to normal bone marrow cells. Immunophenotypic analysis revealed a marked antigenic heterogeneity in AML, also evident within single FAB subclasses. However, leukaemic cells of FAB subclass M1 significantly more often expressed HLA class I antigen than those of FAB subclass M5a, whereas Fc gamma receptors which were expressed only on a few cells in M5a, were increasingly frequent on leukaemic cells of M1-M2, M4, and M5b leukaemias. The frequency of cells reacting with the monoclonal antibody T50/12,11,2 was related to the complete remission rate of the patients. Patients with high frequencies of cells reacting with this antibody had a better complete remission rate than patients with fewer cells binding to this antibody. The immunophenotypic heterogeneity an AML may reflect a great biological variability of this disease. This variability may be of importance for the classification and treatment of AML.

Adult↗

Leukemic myeloblasts expressing lymphoid markers.

Out of 60 patients with acute myeloid leukemia not preceded by chronic myelocytic leukemia or any preleukemic phase, 7 had both lymphoid and myeloid markers. All patients expressed common acute lymphatic leukemia antigen (CALLA) in 20% or more of their leukemic cells, which also showed positive peroxidase reaction. In addition, 4 patients had Auer rods. Two additional patients had morphologically clear acute monocytic leukemia (FAB M5b) and cells expressing CALLA. In 4 of the 7 patients the sum of the percentages of peroxidase or Leu M1 + and CALLA-positive blast cells exceeded 100%, suggesting that at least some of the cells had both myeloid and lymphoid markers. Moreover, out of 3 patients where double staining with the CALLA antibody J5 and the myeloid marker Leu M1 was performed, 2 had both markers on the same cells.

Adult↗

Macrophages, NK-cells, NK-like cells, and tumor surveillance in man.

Although every second patient with leukemia or a solid tumor has lymphocytes which can recognize or can be induced to recognize autologous tumor cells, it has been difficult to demonstrate that this recognition is, in man, due to tumor specific antigens. Other immunological abnormalities, such as lineage infidelity or maturation asynchrony, are more likely explanations. Moreover, immunological heterogeneity is pronounced among human tumor cells. For these reasons, antibody independent tumor surveillance is receiving increased attention. It is mediated by cytotoxic macrophages, NK-cells and the so called NK-like, pre-induced cytotoxic T-cells. NK-cells, probably a T-cell subpopulation sharing a marker with macrophages, have a cytotoxic effect mainly on certain cell-lines, but hardly on viable human tumor cells. In contrast, different degrees of pre-stimulation with allogeneic lymphocytes, lectins or interleukin 2 can induce, in human T-cells, both HLA-restricted and non-restricted cytotoxicity against viable human tumor cells. This indication is active even in T-cell populations that are either monoclonal or pre-depleted of NK cells.

Humans↗

Difference between young and old patients in characteristics of leukemic cells: older patients have cells growing excessively in vitro, with low antigenicity despite high HLA-DR antigens.

Fifty-six patients with acute, non-lymphatic leukemia in the initial phase were studied. The poor prognostic signs were excessive in vitro growth, many HLA-DR-positive cells, or a low ratio of leukemic cell antigenicity to HLA-DR positivity and age. The cells from older patients formed more clusters (P less than 0.05), and they had less capacity to stimulate normal allogeneic lymphocytes (P less than 0.05) than those from younger patients. Cells forming many clusters also were more often (P less than 0.01) HLA-DR-positive than those forming few clusters. It is suggested that the prognosis in old patients with acute leukemia is poor in part because their leukemic cells have characteristics different from those of young patients.

Adolescent↗

Cytological and immunological study of 139 patients with acute leukemia.

Sixty-six children with acute lymphatic leukemia (ALL), 26 adults with ALL and 47 adults with acute myeloid leukemia (AML) were subclassified according to the classifications French-American-British (FAB) and World-Health-Organization (WHO). Nine immunological markers and 6 cytochemical stains were also used. The reproducibility of the WHO classification of the smears performed independently twice by one observer was 93%, but that between two observers only 78%. Three patients considered ALL by A were called AML by B, but all three had the common acute leukemia antigen, CALLA. In the group of 87 patients considered ALL by B, only 74 were classified ALL by A, but of the 13 non-ALL B, none had the CALLA. Ten of these thirteen patients had myeloid markers such as Philadelphia chromosomes, peroxidase or Sudan Black B positive reactions, or Fc and C3 receptors. The remaining 3 patients were non-Hodgkin lymphoma with B-cell markers. None of the 47 cases classified as AML had CALLA. Seventeen of nineteen myeloblastic leukemias (M2, FAB) had a myeloid antigen (Mag) and 13 of 15 myelomonocytic leukemias (M4, FAB) had, in addition, Fc and C3 receptors.

Acute Disease↗

Prognostic significance of terminal transferase activity and glucocorticoid receptor levels in acute myeloid leukemia.

A retrospective study was undertaken to evaluate terminal transferase activity and glucocorticoid receptor content as predictors of prognosis in 52 adult patients with acute myeloid leukemia (AML). Eighteen patients who had detectable levels of TdT in their leukaemic cells (greater than or equal to 0.1 unit microgram-1 DNA), had a higher complete remission rate than patients with low TdT activity. Patients below 60 years with increased TdT activity also had longer survival as compared to those with low TdT levels. By combining cytochemical analysis of peroxidase and immunocytochemical staining for TdT it was possible to show that the enzyme was located in leukaemic cells of myeloid origin. Leukemias of monocytic origin had no detectable TdT activity in 10/11 cases. The cellular content of the cytoplasmic glucocorticoid receptor varied from 0 to 2.8 fmol micrograms-1 DNA. There was no difference in receptor content between the different FAB subgroups. High levels of the receptor (greater than or equal to 0.22 fmol microgram-1 DNA) were positively correlated with the remission rate. Patients with TdT levels of greater than or equal to 0.1 unit microgram-1 DNA and a glucocorticoid receptor concentration of greater than or equal to 0.22 fmol microgram-1 DNA had significantly higher remission (P = 0.001) and survival rates (P = 0.007) compared with those with undectectable levels of both TdT and low receptor content. It is thus concluded that combined measurements of TdT and the glucocorticoid receptor are useful predictors of prognosis in AML.

Adult↗

Quality of diagnoses and cost of managing anemia in four countries.

An earlier study of non-hospitalized Swedish patients suggested frequent overprescribing of iron tablets and frequently uncertain diagnoses of iron deficiency. For this reason, a record audit was performed of 202 patients hospitalized because of iron deficiency anaemia or pernicious anemia in an English, a French, three Swedish, and a US teaching hospitals. Results are difficult to interpret because of the limited extent of this study and because differences between hospitals are as great as those between countries. Nevertheless, the Swedish hospital seemed to have 37% longer duration of stays (p less than 0.05), it spent only 16% of the total hospitalization cost for diagnostic studies as compared to 22-35% for the other hospitals, and it had numerically, but not significantly increased percentages both of uncertain diagnoses and of unidentified causes of the iron deficiency. For comparable time periods the hospitals with the longest length of stay also had the highest percentage of uncertain diagnoses (p less than 0.001). After the local publication of the first reports in 1978-1981, an improvement in the percentage of uncertain diagnoses was found in the Swedish hospital, which suggests that quality evaluation can lead to quality assurance.

Anemia, Hypochromic↗

A 10-year follow-up of the National Cancer Act.

No decade has seen as great advances as the 1970's in the understanding of cancer and in treatment results. The discovery of the role of oncogens, of some viruses, carcinogenic chemicals, and life-style in carcinogenesis and the increased cure rates in childhood tumors, leukemias, lymphomas, and breast and testicular carcinomas are some examples. The National Cancer Act must be credited for these advances to an appreciable degree.

Humans↗

The quality and cost of medical care in Sweden.

Swedish examples are used in favor of recent WHO recommendations of quality assurance. Even prior to present efforts at savings, the autopsy frequency in Swedish hospitals dropped 2% per year. Only 31% of Swedish out-patients see the same doctor on subsequent visits, and since few have a personal physician, emergency ward visits increase about 4% per year. Laboratory errors and uncertain diagnoses seem to be of the order of 20%, at least in some conditions.

Costs and Cost Analysis↗

Hereditary ring sideroblastic anaemia and Christmas disease in a Swedish family.

The association of hereditary ring sideroblastic anaemia with Christmas disease in a Swedish family is described. We have studied the transmission of the sideroblastic trait, in relation to HLA groups and Christmas disease, and also evaluated the erythrocyte morphology, uroporphyrinogen-I-synthetase activity and S-ferritin for the detection of latent cases of ring sideroblastic anaemia. The proband had ring sideroblastic anaemia, Christmas disease and haemochromatosis. 3 cases of ring sideroblastic anaemia were found among the 12 family members studied. Using the factor IX deficiency as a marker of the X chromosome, it appeared that autosomal transmission of the sideroblastic trait was most likely. The sideroblastic trait did not seem to be linked to HLA-A3-alloantigen. Erythrocyte morphology was normal in all non-anaemic subjects. S-ferritin was found to be increased in all 3 cases of sideroblastic anaemia as well as in 1 non-anaemic relative. Erythrocyte uroporphyrinogen-I-synthetase was elevated in 10 of the 12 family members; those with sideroblastic anaemia had the highest values indicating that uroporphyrinogen-I-synthetase is of importance in the disturbed haem-synthesis of ring sideroblastic anaemia. This interpretation is supported by the positive correlation between S-ferritin values and the uroporphyrinogen-I-synthetase activity.

Anemia, Sideroblastic↗

The common acute lymphoid leukemia antigen on b cells of chronic lymphoid leukemia and non-Hodgkin's lymphoma.

Fourteen out of 21 non-Hodgkin lymphoma (NHL) and 3/11 chronic lymphoid leukemia cells (CLL) had the common acute lymphoid leukemia antigen (CALLA) All 32 patients had monoclonal B-cell proliferation. The CLL patients had 90% CALLA positive cells while the proportion of their leukemic elements was superior. Lymph-nodes or bone marrow invaded by a B monoclonal tumor cell population of NHL had significantly more CALLA positive cells (42.1 +/- 32.5%) than non-invaded tissues (11.4 +/- 10.3%). In NHL tissues with monoclonal B-cells, lymph-nodes had significantly more CALLA positive cells (56.0 +/- 29.9%) than marrow (23.5 +/- 27.7%). It is well known that the (CALLA) is not specific for ALL. It has been believed to be a differentiation antigen on pre B-cells. The present study confirms that it also occurs on B-cells (2,4,6,7,8,9,10,11).

Antigens, Neoplasm↗

Efficacy of and errors in randomized multicenter trials. A review of 230 clinical trials.

An attempt was made to study the efficacy in and one of the errors of randomized multicenter clinical trials. Efficacy was defined for the present purpose as a statistically significant clinical difference between at least 2 of the treatment arms studied. The error studied was defined here as non-excluded protocol deviations found during a systematic record review. The nature (multicenter randomized trial or un-controlled pilot study) of 8 so-called "breakthrough" studies which seemed particularly important for future cancer treatment was also established. The number of yearly randomized trials seems to have increased by a factor of 10 between 1969 and 1981, as judged by the abstracts published by the American Society of Clinical Oncology. 23% yielded statistically significant results, which is 18% over the 5% expected chance significances. Of 174 papers and abstracts published by one group, only 18 were reviewable original studies. The corresponding figures for another group was 6 of 22. This explains why only 8 scientifically new statistical significances were found in one series of 76 original articles. The mean dose of cytostatics actually given to 192 breast cancer patients varied, as judged by a record review, between 71 and 93% of the protocol doses. These figures agree with the 15-30% of nonexcluded protocol deviations found previously. Of the 8 "breakthrough" studies, 7 were single center pilot studies without randomized controls, and only 1 was a randomized multicenter study. It is suggested that more relevant questions can be asked in multicenter randomized clinical trials if they are based on promising single center pilot results, and that record reviews should be performed so that protocol deviations can regularly be reported.

Antineoplastic Agents↗

Possible mechanisms of immunotherapy action in acute nonlymphocytic leukemia: macrophage production of colony-stimulating activity.

Earlier studies show that immunotherapy (IT) improves prognosis in acute nonlymphatic leukemia (ANLL), and that ANLL cells probably have tumor-associated antigens, for autologous lymphocytes can react to them. Also, IT seems to immunize against allogeneic ANLL cells, but there is no cross-immunity to autologous ones. Moreover, patients immunized against their ANLL cells have no better prognosis than patients not having lymphocytes reacting to their ANLL cells. It has also been suggested that IT causes nonspecific immunostimulation, but IT patient's lymphocytes actually react less than those of patients not given IT. The current hypothesis is macrophage activation: Lymphocyte suppression in IT could be explained by suppressor macrophages. Colony-stimulating activity, produced by bone marrow macrophages, decreases during remission in patients not given IT, but not in IT patients. Numerically, blood cells from patients given IT form more colonies than those from patients not given IT. Three of eight patients given IT had more colonies than the upper normal limit.

Acute Disease↗