[Iron supplementation to pregnant women is again "in"].
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Anemia, Hypochromic↗
Biomedical subjects
N E Hansen
Publications and source records attributed to N E Hansen.
A soluble form of the glycolipid-anchored receptor for urokinase-type plasminogen activator is secreted from peripheral blood leukocytes from patients with paroxysmal nocturnal hemoglobinuria.
The cellular urokinase-type plasminogen-activator (uPA) receptor (uPAR) is a glycolipid-anchored membrane protein thought to be involved in pericellular proteolysis during cell migration and tumor invasion. In the present study, we have identified and characterized two soluble forms of uPAR which have retained their ligand-binding capability. One variant was generated in vitro by treatment of intact normal cells with either a phosphatidylinositol-specific phospholipase C (PLC) or endoproteinase Asp-N. The other soluble uPAR variant was secreted in vivo from peripheral blood leukocytes affected by the stem-cell disorder paroxysmal nocturnal hemoglobinuria (PNH), and was found in the plasma from these PNH patients as well as in the conditioned medium from cultured PNH leukocytes. Under normal conditions, we find no evidence for any shedding or secretion of a soluble uPA-binding counterpart to human uPAR in plasma. Unlike normal leukocytes, the PNH-affected cells do not express uPAR on the cell surface, although they do contain apparently normal levels of uPAR-specific mRNA. The secreted uPAR derived from PNH cells has a mobility in SDS/PAGE that is slightly higher than that of uPAR solubilized by PtdIns-specific PLC or detergent, but resembles that of a truncated, recombinant uPAR variant, which has its C-terminus close to the proposed glycolipid-attachment site, suggesting that the secreted protein has been proteolytically processed for glycolipid attachment. The presence in plasma from PNH patients of such a secreted, hydrophilic form of uPAR lends support to the hypothesis that the lesion underlying the PNH disorder resides either in glycolipid biosynthesis or in the function of an as-yet-unidentified transamidating enzyme assumed to cleave and assemble the truncated uPAR with the preformed glycolipid moiety.
Amino Acid Sequence↗
The receptor for urokinase-type plasminogen activator is deficient on peripheral blood leukocytes in patients with paroxysmal nocturnal hemoglobinuria.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal defect in bone marrow-derived cells and is clinically associated with intravascular hemolysis, hemoglobinuria, and an increased frequency of venous thrombosis. The common denominator of PNH-affected blood cells appears to be a defect in the membrane attachment of proteins normally anchored by glycosyl-phosphatidylinositol (GPI). We report here that the cellular receptor for urokinase-type plasminogen activator (u-PAR) is deficient on affected peripheral blood monocytes and granulocytes from four individuals with PNH as evidenced by chemical cross-linking analysis as well as by immunofluorescence flow cytometry using a monoclonal anti-u-PAR antibody. In contrast, on normal blood monocytes and granulocytes we find significant amounts of u-PAR, which is attached to the plasma membrane by a GPI-anchor as defined by its sensitivity towards a specific phospholipase treatment. By two-color flow cytometry it was shown that deficiency of u-PAR expression paralleled that of another GPI-anchored protein. As u-PAR is involved in the initiation of pericellular proteolysis, the reduced expression of u-PAR on PNH-affected leukocytes led to an overall reduction in the capacity for plasminogen activation by cell-surface-bound urokinase. Whereas the abnormal susceptibility of PNH-affected erythrocytes to lysis by autologous complement has been related to the low expression of three GPI-anchored complement regulatory proteins on the cell surface, we now propose that lack of u-PAR expression on the surface of peripheral blood leukocytes may be causally related to the high incidence of venous thrombosis observed in PNH patients.
Animals↗
Prognostic importance of flow cytometric immunophenotyping of 540 consecutive patients with B-cell chronic lymphocytic leukemia.
Blood mononuclear cells from 540 newly diagnosed, unselected patients with B-cell chronic lymphocytic leukemia (CLL) were examined by immunofluorescence flow cytometry for a panel of surface membrane markers, including IgM and IgD, the monoclonal antibodies anti-CD3, -5, -20, -21, -22, -FMC7, and, for the final 125 patients, anti-CD23. There were 503 CD5+ and 37 CD5- cases. In the CD5+ cases, the cells typically expressed IgM, IgD, CD20, CD21, CD22, and CD23. In univariate analysis, age, clinical stage, IgM-fluorescence intensity, CD23, and FMC7 had significant prognostic importance, with high IgM-fluorescence intensity, high FMC7, and low CD23 expression being associated with a short survival. There was no significant difference in survival between 351 cases expressing IgMD and 55 cases expressing IgM without IgD, or between kappa and lambda light chain monoclonal cases. CD20, CD21, and CD22 had no prognostic importance. In Cox multiple regression analyses, age, CD23, IgM-fluorescence intensity, and clinical stage (International Workshop System) had independent prognostic importance. Thus, besides clinical variables, CD23 and IgM intensity might be useful prognostic markers in the management of CD5+, B-cell CLL. The survival of CD5- patients was on the borderline of being significantly shorter than that of CD5+ patients. The majority of the CD5- cases were FMC7+, CD23-, had strong IgM fluorescence, and had splenomegaly.
Aged↗
[Autologous bone marrow transplantation].
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Bone Marrow Transplantation↗
[Autologous bone marrow transplantation in malignant hematologic diseases].
Autologous bone marrow transplantation (Auto-KMT) involves harvesting of a portion of a patient's bone marrow for subsequent reinfusion and restoration of marrow function following ablative doses of cytotoxic therapy, used in the treatment of various malignancies. The use of autologous rather than allogeneic marrow stem cells reduces the probability of acute graft-versus-host disease and reduces the need for obtaining HLA-matched marrow from limited donor pools. The greatest problem in Auto-KMT involves efficacy of the cytotoxic therapy and the obvious lack of graft-versus-leukemia effect. In addition, a theoretical limitation is that the marrow may contain clonogenic malignant cells, which may be the source of reestablished disease. In absence of phase III clinical trials directly comparing Auto-KMT with conventional therapies in the treatment of most malignancies, its role continues to be poorly defined. In an attempt to identify subsets of patients with leukemia or lymphoma who might benefit from transplantation, we performed this study of recent reports from the literature. It is concluded that the associated mortality is acceptable. At present the indications for Auto-KMT are lymphoma in relapse after conventional therapy and acute myeloblastic leukemia in second remission. It is probable that Auto-BMT will be used in earlier disease stages in the future (first remission).
Adult↗
[Malignant hematologic diseases. Diagnosis and treatment. A clearing report].
The malignant haematological disorders comprise the main groups leukemia, malignant lymphoma and multiple myeloma and the potentially malignant disorders: myelodysplastic syndrome, polycythaemia vera, myelofibrosis and M-component of uncertain significance. The common feature of all these disorders is monoclonality, i.e. they originate from one single cell. Around 2,000 new cases are diagnosed per year in Denmark. Because of the relative small number of patients, complex diagnosis and treatment (especially the possibility of cure on intensive treatment) a high degree of centralization is warranted to secure an evenly distributed high level of patient care and research. The present rules for referral of patients are unsatisfactory. A new referral system is proposed based on a common set of rules, agreed upon by five haematological centers in Denmark and the surrounding region, comprising diagnostic procedures, treatment, research and development for all haematological patients in the area. Based on these common rules (functional centralization) it is decided whether the individual patient can be treated in the primary hospital or should be referred to a center (geographical centralization). Recommendations about diagnosis, treatment and referral are made in this report. Detailed suggestions are given for diseases which may be treated locally whereas no detailed regimens are given for diseases and disease stages which should be centralized. In the latter cases, the main emphasis is placed on a presentation of treatment results.
Denmark↗
Prophylactic effect of self-administered pump-driven subcutaneous IgG infusion in patients with antibody deficiency: a triple-blind cross-over study comparing P-IgG levels of 3 g l-1 versus 6 g l-1.
Eight adult patients with hypoimmunoglobulinaemia were randomly allocated to initiation of low- or high-level IgG-substitution. IgG was administered subcutaneously, at 50 or 150 mg ml-1, 20 ml per infusion, by means of a pocket-portable electric infusion pump. Infusions were given 2 to 4 times weekly for 24 months, with a change of dose regimen after 12 months. The desired plasma IgG levels were reached after a mean lag phase of 3 months (range 1-5 months). The median (and ranges) of the individual mean plasma IgG levels during the ensuing 9-month periods were as follows: high-level period, 6.5 g l-1 (range 6.2-7.8 g l-1); low-level period, 3.2 g l-1 (range 3.0-4.0 g l-1). During the high-level period, compared to the low-level period, there was a significant decrease in the following parameters: 'days in bed at home', 'days missed work' and 'days with fever'. No serious side-effects were observed. It is concluded that a plasma IgG concentration of 6 g l-1 can readily be achieved by subcutaneous IgG substitution, and the prophylactic effect is superior to that obtained with a plasma IgG concentration of 3 g l-1.
Adult↗
Estimation of PI-bound proteins on blood cells from PNH patients by quantitative flow cytometry.
The phosphatidylinositol (PI) bound proteins (acetylcholin-esterase (ACE), decay accelerating factor (DAF), leucocyte function antigen type 3 (LFA-3) and Fc-receptor type III (FcRIII] were estimated by flow cytometry on blood cells from four patients with paroxysmal nocturnal haemoglobinuria (PNH), nine patients with 'non-PNH' haemolytic anaemia, four patients with aplastic anaemia and a reference group of 15 healthy individuals to assess the applicability of flow cytometric measurements in the clinical mapping of the PNH defect. Estimation of DAF on granulocytes or monocytes offered the highest diagnostic sensitivity and specificity and may constitute an easy screening method for the PNH defect. One PNH patient had a negative Ham's test at the time of study and normal or near normal levels of PI-bound proteins on erythrocytes, but reduced expression of DAF and FcRIII on granulocytes and DAF on monocytes. The analytical and biological coefficient of variation for flow cytometric estimation of PI-bound proteins was in the range of 4.8-13% and 12-24%, respectively. Blood samples should be analysed without delay, since storage produced spuriously high results. The results were expressed as molecules per cell after calibration with commercially available standards and validated by comparison with previously reported results obtained by other methods. It is proposed that this way of reporting flow cytometric results should be generally adopted to facilitate comparison of results between laboratories.
Acetylcholinesterase↗
Oral idarubicin in elderly patients with acute myeloid leukemia.
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Aged↗
Anaemia of rheumatoid arthritis: serum erythropoietin concentrations and red cell distribution width in relation to iron status.
Immunoreactive serum erythropoietin concentrations were measured in 35 patients with anaemia associated with active rheumatoid arthritis. Based on an evaluation of stainable iron in the bone marrow (marrow iron grade 0-4) and serum ferritin concentrations (concentrations less than or equal to 60 micrograms/l compatible with iron deficiency) the anaemia was found to be complicated by iron deficiency in 19/35 (54%) of the patients. The mean serum erythropoietin level (57.6 (SD) 27.3) U/l) was sufficiently raised for the degree of anaemia irrespective of the size of the marrow iron stores. Thus the data do not support the contention that suppressed secretion of erythropoietin is involved in the pathogenesis of anaemia of chronic disorders. There was a significant inverse correlation between the haemoglobin concentration and log serum erythropoietin in the patients with rheumatoid arthritis. In the patients with adequate iron stores, but not in the iron depleted patients, there was a tendency for serum erythropoietin concentrations to correlate positively both with C reactive protein and erythrocyte sedimentation rate. Red cell distribution width (mean (SD) 16.3 (1.8)%) was above normal (11.5-14.5%) both in the iron replete and the iron depleted patients, and the mean red cell distribution width values did not differ significantly among the two subpopulations. The plasma lactoferrin concentration (mean (SD) 137.6 (109.9) micrograms/l) was normal and did not differ significantly between the iron deficient patients and those with adequate iron.
Adult↗
[A mini epidemic of varicella zoster virus reinfection at a department of hematology].
Whereas primary infection with varicella zoster virus (VZV) (chickenpox) and reactivation of VZV (shingles) are common and recognized, clinical reinfection with VZV is rare. A little epidemic of presumed reinfection with VZV in six immune-compromised adults is presented here. The epidemic lasted for three months, during which a healthy young woman also developed a primary VZV infection in the form of chickenpox. In the immune-compromised patients, the clinical picture was dominated by disseminated, prolonged and frequently haemorrhagic and necrotic eruptions which may cause diagnostic difficulties. Skin biopsy proved helpful in the diagnosis while demonstration of the VZV antigen in the skin elements was specific and sensitive. All of the patients, with one exception, were treated with acyclovir and dissemination of the infection to the inner organs did not occur. One patient may have died on account of the VZV infection. In conclusion, immune-incompetent patients must be warned against infection from chickenpox or disseminated herpes zoster. In cases of proved exposure, prophylactic treatment with acyclovir should be considered and, in cases of clinical disease, immediate treatment with 10 mg acyclovir per kg body weight should be administered intravenously thrice daily.
Adult↗
Trends in the incidence of multiple myeloma in Denmark 1943-1982: a study of 5500 patients.
The incidence of multiple myeloma in Denmark during the period 1943-82 was examined, based on the files of the Danish National Cancer Registry. A total of 5535 patients (3023 male and 2512 female) were registered. Over the period 1943-62 the incidence increased 2- to 3-fold for both men and women, but the increase in men was steeper and was seen several years before the increase in women in all 5-yr age groups from 50 to 75 yr of age. This pattern would be compatible with an impact of environmental factors. The increase, also percentagewise, rose with increasing age. Since 1963 the incidence has been virtually stable with a possibly decreasing trend during the latest 5- to 10-yr period.
Age Factors↗
Reinfection with varicella-zoster virus in immunocompromised patients.
A small epidemic of varicella/atypical generalized zoster among 6 immunocompromised patients and one previously healthy person is described. The 6 immunocompromised patients suffered from lymphoproliferative diseases in terminal stages treated with chemotherapy and reported varicella in their childhood. They developed a generalized maculopapular rash with hemorrhagic bullae and necroses. The infection passed from one patient to another during a 3-month period in the department. They were placed in adjacent rooms and nursed by the same staff. The most specific diagnostic tool was the detection of varicella-zoster virus antigen from vesicles by ELISA technique. The epidemic was supposed to be caused by exogenous reinfection with varicella-zoster virus, and illustrated that generalized zoster may be even so infectious as varicella and that immunocompromised patients should be protected against reinfection.
Adult↗
[Medical treatment of cancer--an elucidating report].
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Antineoplastic Agents↗
Lactoferrin-mediated transfer of iron to intracellular ferritin in human monocytes.
Interactions of 125I-59Fe-lactoferrin with human monocytes were studied. After 4 hours of incubation, the uptake of 59Fe exceeded that of 125I. In dissociation studies the cellular 59Fe-activity was only partly dissociable during 16 h, whereas the 125I-activity could be released nearly completely. Disruption of the cells and studies on the cytosolic phase were performed employing gel-filtration and affinity chromatography. An appreciable amount of lactoferrin was found in the cytosolic phase. About 50% of the cytosolic 59Fe-activity was bound to ferritin. The results suggest that lactoferrin is internalized into monocytes and that iron is transferred to ferritin. These cellular events may contribute to an understanding of the accumulation of iron in the monocyte/macrophage system observed during inflammatory conditions.
Cells, Cultured↗
High-risk AML evidenced by a monoclonal antibody.
A monoclonal antibody has been raised against a surface membrane antigen present on leukemic myeloblasts. In 52 consecutive patients with acute myeloid leukemia treated in a standardized fashion with intensive chemotherapy the immunologic subclass with respect to this antigen was correlated to the clinical outcome. We found the expression of this antigen to predict a poor prognosis, when measured as survival of CR-patients and as survival after 1st relapse.
Adult↗
Rothia dentocariosa septicaemia in a patient with chronic lymphocytic leukaemia and toxic granulocytopenia.
Rothia dentocariosa is part of the human oral flora and has only rarely been reported as a cause of clinical infection. We report the isolation of Rothia dentocariosa from the blood of a septicaemic patient with chronic lymphocytic leukaemia and bone marrow depression following treatment with clomipramine and zuclopentixol.
Actinomycetaceae↗