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Biomedical subjects

J Hastka

Publications and source records attributed to J Hastka.

At least 19 recordsLinked to original sources

Spontaneous remission in adult acute myeloid leukemia in association with systemic bacterial infection-case report and review of the literature.

Spontaneous remission of acute myeloid leukemia in the adult is a rare event. We report on a 31-year-old male patient suffering from acute myeloid leukemia (AML) M5a according to the French-American-British (FAB) classification with biphenotypic features in flow cytometric examination and severe bacterial infection with group G streptococci at the time of diagnosis. Because of sepsis and stable clinical conditions, chemotherapy was delayed and antibiotics were administered intravenously. Within 6 weeks a spontaneous remission of AML occurred. Remission lasted for about 2 months. At the time of relapse, a change in phenotype of the leukemic blasts with a loss of B-lymphoid markers could be demonstrated by flow cytometry. The patient was treated with an induction therapy according to the multicentric German AMLCG 2000 schedule. To our knowledge, this is the first report of a spontaneous remission in an AML FAB M5a associated with coexpression of myeloid- and lymphoid-associated antigens on the leukemic blasts. Possible mechanisms of this phenomenon are discussed with a review of the literature.

Acute Disease↗

Multilobated nuclei in Waldenström' macroglobulinaemia.

We report a case of Waldenström' macroglobulinaemia, where the bone marrow analysis showed an almost complete infiltration by a heterogeneous population, consisting of 80% small lymphoplasmacytoid cells and 20% large atypical cells with multilobulated nuclei. Both cell populations were CD19+ and CD38+ and contained IgM. Fluorescence in situ hybridization analysis with a chromosome 8 painting probe on interphase nuclei revealed only two signals in each cell, including in those with multiple nuclei. Our findings suggest that the multilobulated nuclear structures are diploid and originate from a single nucleus. In contrast to the published multiple myeloma cases, our patient showed good response to chemotherapy. After successful chemotherapy, the morphology of the lymphoma changed into typical lymphoplasmacytoid lymphoma. The multilobulated population was no longer detectable. Five years after the initial diagnosis, the patient is still alive and in good health.

ADP-ribosyl Cyclase↗

Auer rod-like inclusions in multiple myeloma.

We report a case of IgA multiple myeloma, in which the plasma cells showed multiple azurophilic, Auer rod-like intracytoplasmic inclusions in May-Grünwald-Giemsa-stained marrow smears. Cytochemical stainings revealed a strong alpha-N-esterase activity of these inclusions, whereas the reactions for peroxidase, Sudan black, chloroacetate esterase, and PAS were negative. Immunostaining verified IgA-kappa inside the plasma cells. The inclusions, however, were negative. Amyloid and lysozyme were also not detectable. Electron microscopy showed Auer rod-like inclusions with a smooth surface in the neighborhood of a well-developed rough endoplasmic reticulum, but with no direct relation to it. The inclusions showed a fine lamellar substructure, and the periodicity of the filamentous striations was about 10 nm, comparable with the substructure of typical Auer rods. Our findings suggest that the azurophilic inclusions in multiple myeloma are Auer rod-related structures, which likewise consist of active lysosomal enzymes. In contrast to the Auer rods in acute myeloblastic leukemia (AML), however, the inclusions in multiple myeloma consist of typical plasma cell enzymes.

Azure Stains↗

bcl-2 expression in non-Hodgkin's lymphomas is not associated with bcl-2 gene rearrangements.

Previous reports have associated bcl-2 gene rearrangements found in non-Hodgkin's lymphomas with an inappropriately elevated bcl-2 expression compared with the mature B-cell stage of development. This study investigates bcl-2 expression in non-Hodgkin's lymphomas (NHL) without bcl-2 gene rearrangements. Molecular analysis in 168 patients with NHL revealed 45 patients without bcl-2 gene rearrangements in which additional immunostaining for bcl-2 protein was possible. An unexpectedly high prevalence (39/45) of bcl-2 expression was found. The levels and patterns of bcl-2 expression were not specific for the histological type of NHL and were similar to those shown in comparable cases with bcl-2 gene rearrangements. In conclusion, bcl-2 expression is not specific for NHL bearing bcl-2 gene rearrangements. This finding implicates the existence of other deregulating control mechanisms of bcl-2 expression, more important than bcl-2 gene rearrangements.

Autoradiography↗

Intracellular expression of CD61 precedes surface expression.

We report a case of acute myeloid leukemia which we have classified as acute megakaryoblastic leukemia because of intracytoplasmic expression of CD61. Light microscopy demonstrated agranular blasts which, by cytochemical staining, were negative for myeloperoxidase. Using flow cytometry, the blast cells were seen to be positive for HLA-DR, CD7, CD13, CD33, and CD34, thus revealing their myeloid origin. Immunophenotyping on fixed blood smears additionally showed positive reaction with the CD61 antibody, demonstrating the megakaryoblastic differentiation of the blasts. After permeabilization of the cell membrane, the intracytoplasmic CD61 expression was confirmed by flow cytometry. Cytogenetic analysis disclosed a del(7)(q21-22). Our findings suggest that cytoplasmic expression of CD61 may precede the cell-surface expression of this antigen and should therefore be investigated in all cases of acute leukemias with undifferentiated morphology and negative cytochemistry to set apart early FAB-M7 from FAB-M0.

Aged↗

Micro-column affinity test and gel test: comparative study of two techniques for red cell antibody screening.

BACKGROUND AND OBJECTIVES: We describe the results of a comparative evaluation of a gel test (ID Micro Typing) and a micro-column affinity test (MCAT, Cellbind Screen) for red cell antibody screening and identification under routine conditions. MATERIALS AND METHODS: 3,000 serum samples of patients from the Mannheim University Hospital were tested in parallel by means of the gel test and the MCAT, using the low-ionic-strength-saline indirect antiglobulin test and the protein G affinity technique, respectively. Test cells used were the same in all tests. In addition, we performed titration studies with all detected antibodies as well as with 59 frozen sera containing antibodies of known specificity. RESULTS: A total of 154 antibodies (5.1%) were detected, 149 by gel test and 147 by MCAT. The overall sensitivity and specificity of the gel test was 96.8 and 96.5% and of the MCAT 95.5 and 97.2%. No significant differences between the gel test and MCAT were found when the titer scores of all 213 (fresh and frozen) antibodies were used to check the results. The mean scores for the gel test and the MCAT were 26.8 and 28.5, respectively. For anti-Fy(a) and anti-Kell, a significantly higher titration score could be obtained in the MCAT, whereas anti-Lu(a) showed a significantly higher score with the gel test. CONCLUSION: For the screening of unexpected red blood cell antibodies, the MCAT is as sensitive as the gel indirect antiglobulin test. The sensitivity and specificity of the two systems are more or less the same although it seems that IgM antibodies are better detected by the gel test.

Antibodies, Blocking↗

Laboratory tests of iron status: correlation or common sense?

We demonstrate that simple correlation between the various tests of iron status is not sufficient for examining their value in diagnosing iron deficiency (ID). Three degrees of ID are recognized: Iron depletion (ID grade I) is defined by decreased total body iron and normal iron support to erythropoiesis, as diagnosed by decreased storage iron, decreased ferritin, normal sideroblast count, normal zinc protoporphyrin (ZPP), and transferrin saturation >15%. When the iron supply to erythropoiesis becomes insufficient, as diagnosed by transferrin saturation < or = 15%, increased ZPP, and decreased sideroblast count, iron-deficient erythropoiesis (ID grade II) occurs. When finally hemoglobin is below its normal range, iron-deficiency anemia (ID grade III) results. The various tests for ID cannot be compared without taking into account the severity of the deficiency. Depending on the grade of ID examined, the correlation of markers seen in our patients' data varied considerably. We conclude that a "best" marker of ID does not exist. However, the different tests efficiently complement each other by detecting different stages and individually show the clinical extent of ID. Ferritin reflects the iron stores. ZPP indicates whether the ID in a given patient is clinically relevant or not. Finally, the extent of a clinically relevant ID can be assessed by the measured ZPP, hemoglobin concentration, and red cell indices.

Anemia, Iron-Deficiency↗

Central role of zinc protoporphyrin in staging iron deficiency.

In iron deficiency, zinc protoporphyrin (ZPP) is produced instead of heme, and the ZPP concentration in erythrocytes is increased (normal < or = 40 mumol/mol heme). We investigated the relevance of ZPP for staging iron deficiency. ZPP was determined by hematofluorometry in samples from 103 patients. Nineteen patients with iron depletion showed decreased serum ferritin (12.1 +/- 4.4 micrograms/L) with normal ZPP and hemoglobin (Hb). Twelve patients with iron-deficient erythropoiesis had decreased ferritin (10.4 +/- 2.4 micrograms/L), increased ZPP (72 +/- 9 mumol/mol heme), and normal Hb concentrations. In 72 patients with iron-deficiency anemia, ferritin was < 12 micrograms/L. In mild anemia (Hb between 100 and 120 g/L, and normal erythrocyte indices), ZPP was 100 +/- 16 mumol/mol heme. In severe anemia (Hb < 100 g/L, decreased erythrocyte indices), ZPP values were significantly higher (265 +/- 109 mumol/mol heme). We conclude that measurements of ZPP, ferritin, and Hb can reliably be combined to classify the degree of iron deficiency.

Anemia, Hypochromic↗

Zinc protoporphyrin in anemia of chronic disorders.

Hematofluorometric determination of zinc protoporphyrin (ZPP) is a screening method for the assessment of iron deficiency (ID). Chronic disorders are frequently accompanied by anemias of unclear origin, most probably caused by an impairment of iron metabolism. We investigated the relevance of ZPP for the detection of derangements of iron metabolism in anemias of chronic disorders (ACD). In 19 patients with ACD caused by chronic inflammatory non-neoplastic diseases, ZPP was determined and correlated with ferritin, transferrin saturation, and hemoglobin (Hb). Marrow sideroblast counts and semiquantitative grading of the marrow hemosiderin were performed in all patients to exclude ID and to show the decreased iron bioavailability. In all ACD patients who exhibited the typical laboratory findings of disturbed iron metabolism, such as hypoferremia, decreased transferrin saturation, decreased bone marrow sideroblasts, and increased marrow hemosiderin, strongly elevated ZPP levels were found (131 +/- 23 mumol/mol heme). ZPP returned to normal after successful treatment of the underlying disease. This is shown in three patients with polymyalgia rheumatica. We conclude that the fluorometric determination of ZPP allows detection and quantification of derangements of iron metabolism associated with chronic inflammatory disorders. By recording the derangements quantitatively, ZPP allows monitoring of therapy of chronic inflammatory diseases.

Anemia↗

Washing erythrocytes to remove interferents in measurements of zinc protoporphyrin by front-face hematofluorometry.

Zinc protoporphyrin (ZPP) is determined by hematofluorometry of whole blood to detect iron deficiency in blood donors. In hospitalized patients, ZPP did not correlate with established markers of iron status. We performed 4500 ZPP measurements with the Aviv front-face hematofluorometer in samples from 475 patients and measured ferritin, transferrin saturation, hemoglobin, and erythrocyte indices. We found that the fluorometric determination is affected by substances dissolved in plasma but that this interference can be eliminated by using washed erythrocytes. In validation tests the within-day variation was < 3.5%; the day-to-day variation was < 6.8%. In 130 healthy persons without iron deficiency, ZPP was < or = 40 mumol/mol heme, which we consider a normal value. Mean ZPP in 46 iron-deficient patients was 256 (SD 105) mumol/mol heme (correlation with ferritin: -0.73; with hemoglobin: -0.85; P < 0.001). When washed erythrocytes are used, the hematofluorometric determination of ZPP is sensitive and specific for detecting iron deficiency in otherwise healthy individuals and hospitalized patients.

Blood Donors↗

[Metastatic C-cell carcinoma with bone marrow carcinosis in type IIa multiple endocrine neoplasia (MEN). Diagnostic and therapeutic problems].

The course of the disease in a patient with multiple endocrine neoplasia type IIa over a period of seven years is described. In spite of multiple diagnostic procedures, only a bone marrow biopsy was able to prove metastatic disease. All therapeutic measures, such as combination chemotherapy, sandostatin, bromocriptine, and 131Iodinemethylendiphosphonate-therapy were not effective in reducing tumor load or symptoms.

Adult↗

The importance of granulocyte elastase in haematological diagnosis.

PMN elastase is a useful additional parameter in the differential diagnosis of the leukaemias. In all patients with myelocytic leukaemias there were elevated levels of elastase-alpha 1-proteinase inhibitor (E-alpha 1PI), while in the lymphatic leukaemias complexed elastase levels were decreased. The highest values were found in the peripheral blood plasma and bone marrow plasma of patients with CML. Despite high E-alpha 1PI concentrations there were no signs of bleeding or consumption of plasmatic coagulation factors. In AML a wide range of E-alpha 1PI levels was observed, extending from slightly elevated to four hundred-fold increased. In myeloblastic leukaemias without maturation (FAB M 1) the concentrations of complexed elastase remained below 150 ng/ml. In myeloblastic leukaemias with maturation (FAB M2) the E-alpha 1PI values ranged between 214 ng/ml and 850 ng/ml (means = 402 +/- 69), and in myelo-monoblastic leukaemias (FAB M4) between 450 ng/ml and 720 ng/ml (means = 663 +/- 72). The only case of promyelocytic leukaemia (FAB M 3) exhibited an extremely high value of 4,550 ng/ml, while a monocytic leukaemia (FAB M5) showed an extremely low value of 5 ng/ml. During cytostatic therapy there was a rapid decrease in levels of complexed elastase, with E-alpha 1PI values returning to normal in remission. In recidivating cases there was an increase of E-alpha 1PI levels in AML and a decrease in ALL. There was a correlation between the E-alpha 1PI concentrations in peripheral plasma and leukaemic bone marrow infiltration, so providing a good basis for monitoring remission from leukaemia and indicating relapse. It was also interesting to observe an extremely low E-alpha 1PI level (5 ng/ml) in patients with myelodysplasia. Under Decortin/Plenastril therapy the concentration rose to 50 ng/ml. An E-alpha 1PI level of 10 ng per ml was observed in one case of Ranitidine agranulocytosis. Under corticoid therapy the value returned to normal within eight days.

Clinical Enzyme Tests↗