bluuebunny/crossref_metadata_2025 huggingface dataset:
‘μ’ Heavy Chain Type ‘Non‐Excretory’ Myeloma
Authors: Guglielmo Patrizia , Granata Pasquale , Raimondo Francesco Di , Lombardo Turiddu , Giustolisi Rosario , Cacciola Elio
Published: August 2010

An unusual case of ‘non‐excretory’ myeloma is described in which, using immunofluorescen‐ce, only ‘\i’ heavy chains were detected in almost all bone marrow plasma‐cell cytoplasm. Cytoplasmic light chains were completely lacking, and neither monoclonal whole immuno‐globulin (Ig) nor free heavy nor light chains were detected in serum and urine, although the clinical and morphological features showed the classical pattern of myeloma. The possible mechanism which could play a role in the disturbance of the Ig‐chain secretion observed in this case is discussed.
A Method for the Quantification of Cellular Composition in Lymphoma Biopsies
Authors: Schultz Henrik
Published: August 2010

A method for the classification and quantification of lymphoma cells in non‐Hodgkin lymphomas is described. Lymphoma‐cell types were defined and used in differential counts of haematoxylin and eosine stained paraffin‐embedded sections.

The following cell types were distinguished: small lymphoid cells (small lymphocytes and small plasma cells), medium‐sized lymphoid cells (round, cleaved and cerebriform lymphocytes, and medium‐sized plasma cells), and large lymphoid cells (lymphoblastic, round triple‐nucleolated, and pleomorphic types). The intra‐observer agreement in the classification of cell types was 43–85 %. The agreement in distinguishing small, medium‐sized, and large lymphoid cells was 85–92 %. In differential counts in contrast to conventional histologic classification all cellular profiles were classified regardless of possible tangential cutting. 92 % of the cellular profiles at different sectional planes of the same cells were consistently classified, indicating that tangential cutting of cells only influenced the differential counts to a minor degree. By the quantification of cellular composition in multiple, randomly selected areas, classified as representative at low power magnification, only small intra‐lymphoma variations were observed in contrast to marked inter‐lymphoma variations.

The high reproducibility of lymphoma‐cell types in combination with the small intralymphoma variation makes the quantifiable method suitable in the histological evaluation of non‐Hodgkin lymphomas.
The Production and Availability of Tissue Thromboplastin in Cellular Populations of Whole Blood Exposed to Various Concentrations of Endotoxin
Authors: Østerud Bjarne , Bjørklid Eirik
Published: August 2010

These studies were undertaken to determine the type and availability of the procoagulant activities generated in blood incubated with endotoxin.

The shortening of the recalcification time of blood incubated with endotoxin was directly correlated with the increase in synthesis of tissue thromboplastin in the monocytes. The procoagulant activity which resulted in the shortening of the clotting time was shown to be almost totally blocked by tissue thromboplastin antibodies. Thus, no additional procoagulant activity was generated in platelets during the 5 h incubation of blood with endotoxin. However, lysed platelets enhanced the synthesis of tissue thromboplastin in blood monocytes in the presence of endotoxin. Lysed red blood cells or granulocytes had no such effect. In endotoxin stimulated monocytes the main part of the newly synthesized tissue thromboplastin appeared to be exposed on the cellular surface. Thus, only 25 % of the tissue thromboplastin activity was recovered when tissue thromboplastin antibodies had been present during the stimulation. Unstimulated monocytes were also found to possess tissue thromboplastin activity, but this low activity was not affected by tissue thromboplastin antibodies unless the monocytes were disrupted by sonication. The high percentage of tissue thromboplastin exposed on the surface of the endotoxin stimulated monocytes in whole blood may contribute significantly to the rapid induction of disseminated intravascular coagulation in gram negative sepsis.
Improvement of Some Blood Coagulation Factors in Cirrhotic Patients Treated with Low Doses of Heparin
Authors: Cordova C. , Musca A. , Violi F. , Alessandri C. , Vezza E.
Published: August 2010

Effects of subcutaneous calcium‐heparin and vitamin K administration were studied in 30 cirrhotic patients showing low values of prothrombin time, antithrombin III, fibrinogen, platelet count, plasminogen, a2‐antiplasmin, raised levels of fibrin(ogen) degradation products and prolonged activated partial thromboplastin time. A group of 10 patients was first treated with K vitamin for 15 d; after vitamin K therapy interruption, a treatment with 5000 IU (8000 IU in 1 patient) every 12 h of subcutaneous calcium‐heparin was started. In another group of 20 patients a treatment with 5000 IU (8000 IU in 2 patients) every 12 h of subcutaneous calcium‐heparin was started immediately. The heparin administration in both groups had been performed for at least 2 weeks. No significant changes of blood coagulation picture were observed after vitamin K administration, while calcium‐heparin treatment showed an increase in prothrombin time, fibrinogen, platelet count, plasminogen, a2‐antiplasmin, a decrease in fibrin(ogen) degradation products and a shortened activated partial thromboplastin time. There was no significant change in antithrombin III values.
An Abnormal Inherited Fibrinogen (Fibrinogen Genova) with Delayed Fibrin Aggregation
Authors: Hassan H. J. , Orlando M. , Tonini G. P. , Casalbore P. , Sarti A. , Boeri E. , Giacchino R. , Tentori L. , Mori P. G.
Published: August 2010

A new autosomally inherited dysfibrinogenaemia was recognized in 3 members of an Italian family. No bleeding tendency or thrombotic disease in any of the affected members were demonstrated.

Coagulation tests revealed prolonged prothrombin, thrombin and Reptilase times. Plasma fibrinogen levels were normal with immunologic method and slightly reduced with chrono‐metric assay: the other blood coagulation factors were normal. In addition, cross‐immuno‐electrophoresis performed on patients' plasma was indistinguishable from the normal.

Dysfibrinogenaemia was confirmed by studying the purified fibrinogen. The fibrin polymerization curve, measured spectrophotometrically, showed a lower slope than the normal. A delay in fibrin monomer aggregation was revealed when compared to the normal at an equal concentration. The release of fibrinopeptides was normal. SDS polyacrylamide gel electrophoresis, isoelectric focusing and cross‐immunoelectrophoresis of purified fibrinogen were not able to demonstrate any structural abnormality. The fibrinogen was named fibrinogen Genova.
A Case of Severe Aplastic Anaemia Successfully Treated by Retransplantation from the Same Donor
Authors: Noguchi Koji , Ifuku Hideki , Ohe Yokiko , Okamoto Takahiro , Fujita Shigeru , Kanamuru Akihisa , Nagai Kiyoyasu , Kai Shunro , Hara Hiroshi , Uchino Haruto , Yamagishi Shikyu , Yoshida Yataro
Published: August 2010

A 16‐year‐old girl with severe aplastic anaemia was successfully treated with retransplantation of bone marrow from an HLA‐identical sibling after rejection of the first transplantation from the same donor. Cyclophosphamide was used for the first transplantation and cyclophosphamide, 300 rad total‐body irradiation and antilymphocyte globulin were used for the second transplantation. Permanent engraftment was achieved after the retransplantation with normalization of haemopoiesis, which has lasted for over 17 months. The patient is now in excellent clinical condition with minimal signs of chronic graft versus host disease.
Effect of 2 Anti‐Arrhythmic Drugs Aprindine and Moxaprindine on the Replication Capacity of Murine and Human Haemopoietic Cells
Authors: Stryckmans P. A. , Ronge‐Collard E. , Delforge A. , Lambert M. , Suciu S.
Published: August 2010

Aprindine, a potent anti‐arrhythmic agent, occasionally seems responsible for agranulocytosis. In order to study its potential haematological toxicity, 3 different in vitro tests were used: (a) the capacity of human and mice bone marrow to incorporate tritiated thymidine (3HTdR), (b) the capacity of stimulated human blood lymphocytes to incorporate 3HTdR and (c) the capacity of human granulocyte‐macrophage stem cells to form colonies in agar. For all these tests aprindine was found to be toxic at concentrations close to the clinical therapeutic serum concentration.

Moxaprindine, chemically very close to aprindine exhibits also an anti‐arrhythmic activity. It was examined in the same tests in parallel with the study af aprindine. Moxaprindine also exhibited haematological toxicity in the tests but at a significantly higher concentration, approximately twice that of aprindine. Assuming that these in vitro tests are relevant to the in vivo haematological toxicity, moxaprindine could be considered a clinically safer antiarrhythmic agent than aprindine.
Pyridoxine‐Responsive Primary Acquired Sideroblastic Anaemia
Authors: Meier Peter J. , Fehr Jürg , Meyer Urs A.
Published: August 2010

The activity of 5‐aminolaevulinate (ALA) synthase, the first and rate‐limiting of haem synthesis, was markedly reduced (13 % of controls) in erythroblasts of a patient with acquired, primary sideroblastic anaemia (PASA). The reduced activity of ALA synthase could not be restored in vitro with 1 mmol/1 pyridoxal‐5‐phosphate (PLP). Treatment of the patient with pyridoxine for several months increased the ALA synthase activity from 13 % to 50% of controls in the absence and to 100% in the presence of PLP in the incubation medium. These studies suggest that both increased degradation of apo‐ALA synthase and decreased affinity of ALA synthase for PLP may be involved in pyridoxine‐responsive PASA.
Bone Marrow Findings in Infectious Mononucleosis and Mononucleosis‐Like Diseases in the Older Adult
Authors: Krause John R. , Kaplan Sandra S.
Published: August 2010

The bone marrow findings in 5 older adults with infectious mononucleosis or mononucleosis‐like illnesses are presented. These individuals were initially considered to have lymphoproliferative disorders which often have similar constitutional signs and symptoms. All had atypical lymphocytosis of the peripheral blood. In addition, there were also abnormalities in the bone marrow. The most common findings included focal collections of lymphocytes and the presence of granulomas. The granulomas were small without caseous necrosis and giant cells were infrequent. This is in contrast to the idea that the bone marrow is normal in infectious monoculeosis and gives support to performing core biopsies as the aspirate smears in these individuals did not demonstrate the focal lymphocytosis or granulomas. Whereas, infectious mononucleosis and mononucleosis‐like illness may be uncommon in the older individual, they certainly are not rare and it is important to differentiate these benign disorders from the more serious lymphoproliferative diseases. Heterophil test and/or Epstein Barr titers are important confirmatory tests.
Vinblastine‐Induced Erythrocytotoxicity
Authors: Neville Alan J. , Rand Carol A. , Barr Ronald D.
Published: August 2010

At a therapeutic concentration (10−6 mol/l), vinblastine causes no significant changes of erythrocyte morphology in whole blood in vitro, but, with 30% red cell suspensions in buffer, the drug is stomatocytogenic. Several pathogenetic mechanisms are considered and the clinical relevance of this finding is assessed.
Primary Thrombocythaemia in Childhood
Authors: Linch D. C. , Cowan D. , Richards J. D. M. , Wilkinson L. S. , Hutton R. , Moore A. R.
Published: August 2010

Primary thrombocythaemia is described in a 6‐year‐old boy and the literature is reviewed. The features distinguishing primary thrombocythaemia from secondary thrombocytosis are discussed, and the value of platelet function tests and platelet biochemistry are emphasized.
Correlation of Haematological, Electron Microscopic and Cytogenetic Findings in 20 Patients with Preleukaemia
Authors: KANATAKIS STELIOS , CHALEVELAKIS G. , ECONOMOPOULOS TH. , PANANI A. , FERTI A. , VAMVASAKIS E. , ARAPAKIS G.
Published: August 2010

A combined haematological, ultrastructural and chromosomal study was made in 20 patients with preleukaemia. There was evidence of specific correlations between (a) Hb F levels and pancytopenia or profound anaemia, (b) chromosomal and electron microscopic findings and (c) thrombocytosis and ringed sideroblasts. The above findings might be of importance in identifying subgroups of preleukaemic patients with different prognosis.
Dipeptidylaminopeptidase IV (DAP IV) Activity in Normal and Malignant T‐Cell Subsets as Defined by Monoclonal Antibodies
Authors: Wirthmüller R. , Dennig D. , Oertel J. , Gerhartz H.
Published: August 2010

The activity of dipeptidylaminopeptidase IV (DAP IV) was investigated by a cytochemical method in isolated fractions of normal peripheral blood mononuclear cells and malignant cells from 9 patients with chronic T‐cell leukaemia. A positive DAP IV reaction was observed in 52 % of normal T cells, a consistent negative reaction in normal B cells and monocytes. 2 distinct T‐cell subsets, helper/inducer cells (T4+/T8‐) and cytotoxic/suppressor cells (T4‐/T8+), were negatively selected by complement‐mediated cytolysis utilizing the monoclonal antibodies OKT4 and OKT8. On examination of these T‐cell subsets a positive DAP IV reaction was restricted to the majority of normal T4+/T8‐ cells. The malignant cells from 3 patients with T‐chronic lymphocytic leukaemia, expressing the cytotoxic/suppressor pheno‐type (T4‐/T8+) lacked DAP IV activities. In contrast, almost all leukaemic cells from 3 other cases, expressing the helper/inducer phenotype (T4+/T8‐), were strongly positive. Despite their T4+/T8‐ phenotype, the malignant cells from 3 patients with Sezary syndrome were completely DAP IV negative. These findings suggest that the DAP IV reaction may be helpful in the further characterization of normal and malignant T‐cell subsets.
Immunological Studies of PK and PFK Deficiencies Induced by Chemotherapy
Authors: Etiemble Jeanne , Picat Christiane , Boivin Pierre
Published: August 2010

Pyruvate kinase (PK) and phosphofructokinase (PFK) erythrocyte deficiencies induced by chemotherapy were studied in 6 patients. From immunological tests it may be assumed that the PK and PFK deficiencies were due to different direct mechanisms: a disturbance of the synthesis of one of the PFK subunit; mutation(s) in the structural gene of PK which result in the synthesis of mutant proteins. Several molecular mechanisms are probably at the origin of all the disturbances induced by chemotherapy in the red blood cells. The study of these alterations which mimic those detected in preleukaemic and leukaemic states, provides information on the molecular events in the possible production of chemo‐induced cancers.
Increased Levels of Myeloid Progenitor Cells in the Blood of Patients with Metastatic Invasion of the Marrow
Authors: Delforge Alain , Caluwe Jean P. De , Rongé‐Collard Elisabeth , Mattelaer Marie A. , Spiro Théodore , Van den Heule Bernard , Stryckmans Pierre A.
Published: August 2010

Granulocyte‐macrophage clusters and colony‐forming cells (CFU‐C) in the peripheral blood have been studied in 26 cancer patients with neoplastic bone marrow involvement. The concentration of CFU‐C in the blood of normal individuals and of cancer patients with no bone marrow invasion, ranged from 0 to 99 ml. In contrast, out of 27 cancer patients with marrow invasion, 9 (35%) showed a significant increase of blood CFU‐C (100 to 21000/ml) and of those 5 (19%) showed an increase of blood colonies (41 to 9000/ml). There was a strong correlation between increased CFU‐C or colony concentration and the presence of myeloid or/and erythroid immature cells in the peripheral blood. On the other hand, there was no apparent correlation between an increased CFU‐C level and anaemia or abnormal blood leucocyte count or marrow fibrosis. These observations suggest that bone marrow involvement by neoplastic cells may cause spatial redistribution of the grnulocyte macrophage progenitor cells.
The Effects of Cisplatin on Normal Human Erythrocytes in Vitro
Authors: Dawson Margaret , Brown Esther A. , Barr Ronald D.
Published: August 2010

Therapeutic administration of cisplatin is often followed by anaemia which may not be due entirely or even largely to myelosuppression but rather to drug‐induced haemolysis. Similar experience with other cytotoxic agents prompted earlier investigations which yielded evidence of drug‐induced changes in RBC shape in vitro. Current studies of cisplatin and bleomycin, which have been used together in clinical practice, revealed a significant alteration in the profile of RBC morphology; specifically a reduction in the number of ‘bowl’ shaped cells. However, this finding is in contrast to the increase in ‘bowls’ which was observed previously with other drugs. So it appears that direct erythrocytotoxicity cannot explain the occurrence of anaemia in patients who receive cisplatin. An alternative mechanism, similar to that of penicillin induced haemolysis, is suggested by immunoradiometric assays of surface IgG on red cells.
High Dose Intravenous IgG Reduces Platelet Associated Immunoglobulins and Complement in Idiopathic Thrombocytopenic Purpura
Authors: Winiarski Jacek , Kreuger Anders , Ejderhamn Jan , Holm Göran
Published: August 2010

4 children with idiopathic thrombocytopenic purpura were treated with high dose i.v. IgG. Platelet associated immunoproteins were determined with an Elisa technique. Platelet counts increased in all patients, while simultaneously platelet associated IgG, IgA, IgM, C3 and C4 decreased. Serum antiplatelet antibody increased during treatment suggesting that administration of high doses of IgG interferes with the binding of antiplatelet antibody.
Competing Models for the Analysis of Red Cell Survival Obtained with 51Cr Labelling Technique
Authors: Barosi G. , Baraldi A. , Bonomi F. , Cazzola M. , Dacco M. , Spriano P. , Stefanelli M.
Published: August 2010

A computer program for the analysis of 51Cr labelled red cell survival data was used in 84 patients and 8 normal subjects to estimate the parameters of 7 competing models derived from different hypotheses of the red cell destruction process. The purpose was to establish the optimal complexity of a red cell survival model to be used. Senescence or random destruction were the most common identified patterns of red cell death (79% of the cases). Models assuming different levels of death probability according to the age of cells, or 2 populations of cells with different death probabilities, were selected in 21% of the cases. These latter patients were characterized by the lowest values of MRCL. The conclusion of the work was that an automatic procedure for selecting the best model of red cell destruction is necessary when information concerning the mechanism of red cell death is required. For the more practical aim of obtaining an accurate measurement of the MRCL, the minimal set of competing models should account of at least 2 different populations of cells in addition to the random or senescence destruction models.
In Vitro Clonogenic Assays in Selective Neutropenia
Authors: Brown R. D. , Yuen E. , Kronenberg H. , Rickard K. A.
Published: August 2010

Granulocyte‐monocyte colony forming cell (GM‐CFC) concentration and the proportion of GM‐CFC in DNA synthesis (S) were determined in 43 patients with varying degrees of selective neutropenia, including 5 patients who were normal extremes (2.0–2.5 times; 109 neutrophils/1), to study the diagnostic and prognostic significance of clonogenic assays and to determine the response of the committed myeloid stem cell to neutropenia. The proportion of GM‐CFC in S proved to be a more useful parameter than the GM‐CFC concentration. 75% of the patients with greater than 60% GM‐CFC in S returned to normal within 1 month. Patients with less than 20% GM‐CFC in S had at least a 10 times greater incidence of developing a malignant or autoimmune disease than the other 28 patients. The 11 patients with 41–51% in GM‐CFC in S had greater than 1 times; 109 neutrophils/1 and no significant clinical problems but all have remained mildly neutropenic for a long period. An indirect relationship existed between the degree of neutropenia and the proportion of GM‐CFC in S (r = ‐0.70).
Functional Studies on Lymphocytes from Two Siblings with Congenital Hypogammaglobulinaemia
Authors: Tauris Palle , Hansen Peter Wendelboe
Published: August 2010

Two brothers with hypogammaglobulinaemia classified as common variable immunodeficiency (CVID) were investigated for distribution of peripheral blood lymphocyte (PBL) subpopulations, DNA synthesis and plaque‐forming cell (PFC) capability of pokeweed mitogen (PWM) activated autologous and allogenic cocultures. Both patients had a decreased absolute number of T cells and normal or elevated levels of surface immunoglobulin (SmIg) bearing cells.

Isolated B cells cocultured with autologous or allogeneic 4000 r irradiated T cells responded subnormally to PWM monitored by the 3H‐thymidine incorporation in microcultures whereas B cells cocultured with allogeneic untreated normal T cells proliferated normally.

PBL from parallel macrocultures of unfractionated or T/B separated patients' cells were not able to produce plaques using a reversed haemolytic protein A assay. Addition of glucocorticoid to unfractionated PBL did not reverse the unresponsiveness. In allogeneic co‐cultures patients' untreated or 2000 r irradiated T cells induced a normal PFC response. Normal untreated T cells induced a reduced number of IgM‐ and IgG‐PFC from patients' B cells but this response was almost eliminated using irradiated normal T cells.

These results demonstrate a primary B cell defect in the patients and indicate an impaired cooperation between patients' B and T cells. Activation of patients' B cells to Ig secretion requires the presence of proliferating T cells.
Folic Acid Deficiency in β‐Thalassaemia Heterozygotes
Authors: Castaldi G. , Bagni B. , Trotta F. , Menegale G. , Cavallini A. R. , Piffanelli A.
Published: August 2010

Plasma and red cell folate mean contents have been found to be significantly lower in 41 symptom‐free β‐thalassaemia heterozygotes than in 21 controls. Such decreases must be considered as effects of an increased folate utilization caused by the enhanced total, both effective and ineffective, erythropoiesis.

Since no close correlation has been found between packed cell volume and plasma or red blood cell folate levels, it seems that in ‘healthy’ β‐thalassaemia subjects, the degree of anaemia is not influenced by folate body reserves. However, the frequent finding of reduced red cell folate contents suggests that further folate imbalance might lead to clinically significant degrees of folate deficiency.
Fetal Thymidine Kinase (TK1) in Hairy Cell Leukaemia
Authors: Ellims Peter H. , Gan T. Eng , Weyden Martin B. van der
Published: August 2010

The thymidine kinase isoenzyme profile was determined in peripheral blood mononuclear cells and splenic tissue from 4 patients with hairy cell leukaemia, in order to assess the proliferative state of the hairy cell. The predominance of TK1 activity in all 4 spleens and in 2 out of 3 peripheral blood mononuclear cells examined, indicates that the hairy cell has significant proliferative capacity when compared to the neoplastic cell in other chronic lymphoproliferative disorders. It is suggested, in viev of the heterogeneity in peripheral blood mononuclear TK isoenzyme types, that more extensive studies are warranted to examine the relationship between peripheral blood mononuclear TK1 activity and the occurrence of progressive disease in post‐splenectomy patients.
Increased Incidence of Glanzmann's Thrombasthenia in Jordan as Compared with Scandinavia
Authors: Awidi Abdalla S.
Published: August 2010

12 Jordanian patients from 9 families with Glanzmann's thrombasthenia are described. All of them are products of consanguinous marriages. All cases are children with varying severity of mucosal bleeding. The clinical and laboratory findings are described. The importance of consanguinity is discussed and emphasized. Glanzmann's thrombasthenia is the second most common inherited haemorrhagic disorder in Jordan.
Hormonal Dependent Thrombotic Thrombocytopenic Purpura (TTP)
Authors: Holdrinet R. S. G. , Pauw B. E. de , Haanen C.
Published: August 2010

This report presents the case history of a 27‐year‐old woman who developed Thrombotic Thrombocytopenic Purpura (TTP) in the 12th week of her first pregnancy. TTP was successfully controlled with plasma infusions. When plasma infusions were tapered off, TTP relapsed and was followed by eclampsia and fetal death. Plasma infusions were reinstituted until 3 d after delivery. She later suffered relapses manifested by falls in platelet count and haptoglobin level coinciding with the use of an oral contraceptive. After stopping the pill, fluctuations in platelet count and haptoglobin level were observed synchronous with the menstrual cycle (cyclic TTP). The case history described provides evidence for hormonal influences in the genesis of TTP.
Alpha‐Heavy Chain Disease
Authors: Sala Pierguido , Tonutti Elio , Mazzolini Saulle , Antonutto Guglielmo , Bramezza Maria
Published: August 2010

The occurrence of alpha‐heavy chain disease in an Italian adult, working in Libya, is reported, characterized by a spontaneous clinical and immunological recovery. It is suggested that the patient could have acquired the disease during his stay in an endemic area of alpha‐heavy chain disease, and that the observed spontaneous remission could be related to the removal of environmental pathogenic factors, following his departure from Libya.
Incidence of Acute Leukaemia in Norway 1957–1981
Authors: Lund Eiliv , Lie Sverre O.
Published: August 2010

The study is based on the material of acute leukaemia in Norway 1957‐81 from the Cancer Registry of Norway. The age‐adjusted incidence rates for both sexes have been unchanged. For childhood leukaemias (0–14 years at diagnosis) the age‐specific incidence rates have been constant for both sexes and there has been an almost constant incidence for the 5 year birth cohorts 1950‐69. Among adults there has been virtually unchanged age‐specific incidence rates for most age‐groups between 15 and 74 for both sexes. Among those older than 75 years, an increase is seen, most probably due to better diagnostic procedures. No geographic differences were found in age‐specific incidence rates.
Myeloperoxidase‐Deficient Polymorphonuclear Leucocytes
Authors: Bendix‐Hansen Knud , Nielsen Henning Kaspersen
Published: August 2010

Myeloperoxidase (MPO) activity of blood granulocytes was estimated in 96 cases of acute myeloid leukaemia (AML), in 35 patients obtaining complete remission and in 14 of these patients during later relapse. As the pretreatment value of MPO activity was the same in patients who died before obtaining remission as in patients obtaining complete remission, determination of MPO‐deficient PMN has no prognostic value with respect to the probability of obtaining complete remission. While half of the untreated patients had increased numbers of MPO‐deficient PMN in the blood, all patients in complete remission had normal MPO activity (P = 0.0002). A normalization of the MPO activity after induction therapy, therefore suggests remission. Positive correlations could be demonstrated between an initially abnormal MPO activity and abnormal activity at relapse as well as between an initially normal MPO activity and normal activity at relapse (P = 0.0004).

It is concluded that determination of the % of MPO‐deficient PMN in the blood, may be a useful indicator of complete remission in AML, and in serial determinations during the remission phase also an indicator of threatening relapse.
CCNU Toxicity After an Overdose in a Patient with Hodgkin's Disease
Authors: Hörnsten Per , Sundman‐Engberg Britt , Gahrton Gösta , Johansson Bo
Published: August 2010

An overdose of CCNU (600 mg over a 15‐d period) was unintentionally ingested by a patient with advanced Hodgkin's disease subjected to combination chemotherapy. A severe bone marrow depression occurred 3 weeks after the start of the CCNU treatment. The nadir of the platelet count was reached after 4 weeks and that of the granulocyte count after 5 weeks. At the nadir of the white blood cell count, colony‐forming cells (CFU‐C) were found in significantly reduced numbers in the bone marrow, and were not found at all in the peripheral blood; the amount of colony‐stimulating activity (CSA) produced by peripheral blood cells was reduced. However, the cells producing CSA recovered earlier than the CFU‐C, and the CSA peak value was reached about 1 week before the peak value for CFU‐C in the bone marrow. Thus, in vivo CSA‐producing cells appeared to be more resistant to CCNU than were CFU‐C, and their recovery appeared to be a prerequisite for the recovery of CFU‐C and myelopoietic cells.
Hydrocortisone — A Possible Physiological Regulator of Human Granulopoiesis
Authors: Barr Ronald D. , Koekebakker Marijke , Milner Ruth A.
Published: August 2010

The effect of hydrocortisone (HC) on the formation of granulocyte‐macrophage (GM) colonies was assessed in vitro in cultures of normal human bone marrow. Subphysiological concentrations (≤ 10−8 mol/l) of HC had no impact on GM colony formation, but at physiological and therapeutic levels (10−7 mol/l‐10−5 mol/l) the hormone stimulated the production of an increased number of colonies. By contrast, physiological concentrations of progesterone (10−9 mol/l‐10−7mol/l) were without effect and even at 10−6 mol/l there was no influence of progesterone alone on GM colony formation. However, progesterone at 10−6 mol/l inhibited the stimulant effect of HC to a degree which was related inversely to the concentration of HC and the duration of the culture interval. The data from this study suggest that the neutrophilia which accompanies glucocorticosteroid therapy is matched by an increase in the production of granulocytes and that HC may play a rôle, which is mediated by steroid receptors, in the physiological regulation of human granulopoiesis.
The prolonging effect of Soybean Trypsin Inhibitor on the thrombin clotting time
Authors: ARNESEN H. , KIERULF P. , GRAVEM K.
Published: August 2010

Urokinase‐induced fibrinogenolysis was monitored with thrombin clotting time, and inhibited by adding Soybean Trypsin Inhibitor (STI). Depending on the concentration of STI (dialysed or non‐dialysed), the thrombin clotting time was always immediately prolonged upon the addition of STI. At a concentration of 0.2–0.5 mg/ml (final conc.) no progressive prolongation of the thrombin clotting time occurred, indicating inhibited fibrinogenolysis.

By monitoring a mixture of purified human fibrinogen, thrombin and various amounts of STI, with quantitative N‐terminal analysis, the thrombin clotting time prolonging effect of STI was further examined. N‐terminal glycine increase, reflecting fibrin formation rate by thrombin, was unaffected by STI, whereas visible gelation occurred more slowly in the presence of STI.

Thus, STI (or a non‐dialysable contaminant) acts as a fibrin polymerization inhibitor, and not as an anti‐thrombin, even at concentrations regularly used to inhibit fibrinogenolysis in plasma.
Lyophilized, reconstituted plasma as substrate for thrombin activity assays
Authors: BROSSTAD F. , ELDE A.T. , GODAL H.C.
Published: August 2010

Due to more precise readability of the visual gel point, citrated pooled plasma is a better substrate than is purified fibrinogen for thrombin activity assays. Since a lyophilized plasma would be more practical in this context, we have studied whether citrated plasma can be lyophilized and reconstituted without jeopardizing its properties as a thrombin‐assay substrate. While undialysed, lyophilized/reconstituted plasma proved unsuccessful due to a considerable pH shift, the clotting properties of pooled human citrated plasma could be fully preserved if the plasma prior to freeze‐drying/reconstitution was dialysed against a citrate‐NaCl‐diemal buffer pH 7.4 Such plasma could be kept at room temperature for at least 6 weeks or at –20 °C for 18 months and could, subsequent to reconstitution, demonstrate thrombin substrate properties identical to those of freshly prepared plasma.
Myeloperoxidase‐Deficient Polymorphonuclear Leucocytes
Authors: Bendix‐Hansen Knud , Nielsen Henning Kaspersen
Published: August 2010

Neutrophil myeloperoxidase (MPO) activity was analysed semi‐quantitatively both by (i) MPO‐scoring of polymorphonuclear leucocytes (PMN) and (ii) counting the MPO‐deficient PMN (PMN lacking MPO) in 164 subjects (60 cases of leukaemia and 104 normal humans). The scoring method showed that 10 out of 21 (48%) cases of acute myeloid leukaemia (AML), 2 out of 10 (20 %) cases of chronic myeloid leukaemia (CML), 0 out of 29 cases of lymphoid leukaemia (ALL + CLL), and 1 out of 104 normal humans had decreased MPO scores. These figures correlated well with the more simple counting of PMN lacking MPO in the same groups: 8 out of 21 (37 %) cases of AML, 6 out of 10 (60 %) cases of CML and 0 out of 29 cases of lymphoid leukaemia showing more than 4 % PMN lacking MPO. In cases of otherwise unclassifiable acute leukaemia, a decreased MPO score and an increased number of MPO‐deficient PMN suggests the diagnosis of AML and not ALL. Counting the number of PMN lacking MPO was found to be a time‐saving and even more reliable method than the semiquantitative scoring of MPO activity in PMN.
The Biochemical and Clinical Consequences of 2′‐Deoxycoformycin in T Cell Chronic Lymphocytic Leukaemia
Authors: Hallam Lynne J. , Van Der Weyden Martin B. , Ackland Stephen P. , Bagnara Aldo S. , Whiteside Maxwell G.
Published: August 2010

The mechanisms for cell toxicity with adenosine deaminase inhibition by 2′‐deoxycoformycin (dCF) in non replicating lymphoid cells include S‐adenosylhomocysteine (SAH) hydrolase inactivation and reduction of cellular ATP content. These postulates were explored in a patient with T‐CLL receiving dCF with a resultant fall in peripheral blood lymphocytes from 740 times 109/1 to 90 times 109/1 over 15 d. In red cells there was complete inhibition of adenosine deaminase and SAH hydrolase activities, progressive deoxyadenosine triphosphate (dATP) accumulation and ATP depletion but no significant alteration in adenosine monophosphate (AMP) deaminase activity or distribution in purine intermediates from radioactive adenosine. In T‐CLL lymphocytes, there was incomplete lymphoid SAH hydrolase inactivation, reduced AMP deaminase activity and progressive dATP accumulation. The limited decrease in lymphocyte ATP content was related more to dCF administration than dATP accumulation, nor accompanied by significant changes in the distribution of purine intermediates from adenosine. These findings suggest that ATP depletion with dCF therapy does not reflect AMP deaminase activity modulation nor is of critical importance for cell toxicity. The exact role for elevated cellular dATP content and SAH hydrolase inactivation in this toxicity remains to be established.
Long‐Term Follow‐Up Study of 168 Patients with Immune Thrombocytopenia. Implications for Therapy
Authors: den Ottolander G. J. , Gratama J. W. , de Koning J. , Brand A.
Published: August 2010

A total of 168 patients (90 adults, 78 children) with immune thrombocytopenia (ITP) and a median follow‐up of 75 months were treated with a sequential regimen of corticosteroids (n = 125), splenectomy (n = 83) and immunosuppressives (n = 25). In 43 patients an observation period of a minimum of 1 month preceded the therapy. It is concluded that: (i) withholding therapy in the expectation of spontaneous recovery is at least in children justified in case of limited bleeding tendency; (ii) corticosteroids should be limited in adults to a maximum of 3 weeks and in children to a maximum of 6 weeks; (iii) if corticosteroids fail, splenectomy remains the therapy of choice, especially in patients aged ≤ 30 years, and should be performed within 6 months after diagnosis; (iv) after failure of the forementioned forms of therapy, there is rarely a beneficial effect of treatment with azathioprine and vincristine; (v) no reaction to any form of therapy can be followed by an acceptable long‐term outcome.
The relationship between growth in agar, karyotype and prognosis in acute leukaemia
Authors: Gustavsson Anita , Mitelman Felix , Olofsson Tor , Olsson Inge
Published: August 2010

The growth pattern in agar culture and the karyotype of bone marrow cells were studied in 79 patients with untreated acute non‐lymphocytic leukaemia (ANLL). Results were divided into the following groups: (A) colony and cluster formation; (B) growth of less than 600 small clusters per 105 cells; (C) growth of more than 600 small clusters; (D) no growth in agar. Cytogenetically, the patients were divided into 3 categories: NN, normal metaphases only; AN, both abnormal and normal metaphases and AA, abnormal metaphases only. An association was seen between growth pattern and karyotype: the majority of NN patients (33/37) belonged to group (A+B) while in group (C+D) 20/24 patients were AN or AA. 37 patients were prognostically evaluable. The growth pattern in agar but not the cytogenetic pattern had prognostic implications. 25 patients with acute lymphocytic leukaemia (ALL) were also studied at diagnosis. Different growth patterns in agar had no impact on prognosis. No relationship was detected between growth pattern and karyotype in ALL.
Ultrastructural localization of acid alpha‐naphthylacetate esterase in human normal and neoplastic lymphocytic and monocytic cells and in hairy cells
Authors: Boesen Anne Marie
Published: August 2010

The ultrastructural localization of acid alpha‐naphthylacetate esterase (ANAE) activity was studied in normal and neoplastic human monocytic and lymphocytic cells including hairy cells. Normal monocytes and malignant monocytic cells from cases of AML‐M4 and ‐M5 (FAB‐classification) displayed fundamentally the same ANAE staining pattern with reaction products localized to the external surface of the plasma membrane and to small vesicles close to this membrane, more rarely to larger intracytoplasmic vesicles containing endocytosed material or cellular debris. The enzyme activity of the neoplastic cells increased with morphological differentiation. Certain normal blood lymphocytes and T cell‐derived CLL cells showed the reaction product associated with paranuclearly located clusters of vesicular structures, extending from the membranes into the adjacent cytoplasm. Gall bodies were often found in the vicinity and were invariably positive for ANAE. Now and then, plasma membrane activity was present, but never as pronounced as in monocytes. Hairy cells demonstrated a pattern of reaction very similar to that of monocytic cells, whereas B cell‐derived CLL cells and lymphoblasts of T‐ and common type ALL were generally non‐reactive.
Erythroid and granulocyte‐macrophage colony formation in myelodysplastic syndromes
Authors: Ruutu Tapani , Partanen Seija , Lintula Riitta , Teerenhovi Lasse , Knuutila Sakari
Published: August 2010

Colony formation by haematopoietic progenitors from the bone marrow was studied in 44 patients with a myelodysplastic syndrome. Erythroid progenitors BFU‐E and CFU‐E were cultured in methyl cellulose, and granulocyte‐macrophage precursors CFU‐GM in agar. 3 of 32 patients showed normal numbers of BFU‐E colonies; in all the other cases the number of these colonies was below the normal range. CFU‐E colony formation was subnormal in all cases. 23 of 44 patients grew normal numbers of colonies and clusters in CFU‐GM cultures. These patients had refractory anaemia with ring sideroblasts (FAB‐classification) or 5q‐ karyotype anomaly in the marrow. Patients lacking both of these findings exhibited reduced colony formation or excessive growth of colonies and/or clusters, with few exceptions. In conclusion, we found that erythroid colony formation was defective in all cases. Normal granulocyte‐macrophage colony formation was associated with refractory anaemia with ring sideroblasts or the presence of 5q‐ karyotype anomaly.
Ph1 positive blast crisis of chronic myeloid leukaemia exhibiting features characteristic of early T blasts
Authors: Herrmann F. , Komischke B. , Kolecki P. , Ludwig W. D. , Sieber G. , Teichmann H. , Rühl H.
Published: August 2010

Leukaemic cells from a patient in the blast crisis of chronic myeloid leukaemia were subjected to a surface marker analysis using a panel of monoclonal antibodies recognizing differentiation antigens of myeloid (MY7, MY906, VIM D5, MØ P9), erythroid (VIE G4), megakaryocyte (AN51), T‐lymphoid (WT1, 10.2, OKT3, OKT4, OKT6, OKT8, OKT11A) and B‐lymphoid cells (B1, B2, Y29/55), common ALL‐antigen (VILA1), non‐lineage‐ restricted antigens (OKT9, OKT10), monomorphic HLA‐DR determinants (7.2) as well as TdT. When the patient entered his first blast crisis, his blasts expressed a phenotype corresponding to an immature myeloid cell (7.2+, MY7+, My906+, VTM D5‐). Ph1‐ chromosome‐positive blasts from this patient's first relapse had completely changed their surface marker characteristics: they had become TdT‐positive and exhibited surface features characteristic of early T blasts (WT1+, 10.2+, OKT9+, OKT10+, 7.2‐, OKT6‐). Together, these features provide evidence that myeloid cells may share a common precursor with T cells.
Testicular function in young men in long‐term remission after treatment for the early stages of Hodgkin's disease
Authors: Specht Lena , Geisler Christian , Hansen Mogens Mørk , Skakkebæk Niels E.
Published: August 2010

16 young men in long‐term remission after standard treatment for the early stages of Hodgkin's disease were examined for testicular function 48 to 125 months after termination of therapy. The patients had received mantle field irradiation, plus either irradiation of infradiaphragmatic lymph nodes (7 patients) or 6 cycles of MOPP (9 patients). 5 patients had almost normal semen quality judged by seminal fluid analysis. 11 patients had reduced semen quality (8 severely reduced) and often elevated FSH values. Semen samples of poor quality were significantly more common in patients treated with MOPP (7/9) than in those treated with infradiaphragmatic irradiation (1/7). One patient showed signs of regeneration of spermatogenesis. None had experienced reduction in libido and sexual performance after therapy; correspondingly, none had below normal testosterone values or elevated LH values. Patients should be informed about the risk of infertility before treatment. If in a given case several treatment options with equal prospective antineoplastic effect are weighed against one another, the patient's possible desire to retain fertility should favour the use of radiotherapy as opposed to chemotherapy, especially including alkylating agents.—
Yeast cell phagocytosis by mononuclear leucocytes from peripheral blood: Significance of the substrate
Authors: Rydgren Lars , Norberg Bo
Published: August 2010

Lymphoprep®‐isolated mononuclear leucocytes (L‐MNs) from peripheral blood of healthy donors were mixed with yeast cells and filmed by time‐lapse microcinemato‐graphy in glass chambers at +37°C. The concentration of L‐MNs and yeast cells was lowered so as to make directional L‐MN movement (chemotaxis) a necessary conditon of phagocytosis. 54 cases of phagocytosis were filmed. Only yeast cells lying immobile on the glass surface were engulfed. In addition, 11 collisions between free‐floating yeast cells and glass‐adherent L‐MNs were noted. None of these collisions led to immediate engulfment. It is suggested that the process of phagocytosis requires prolonged leucocyte‐prey contact, in the order of magnitude of 3 to 5 seconds.—
Granulopoietic precursors in chronic neutropenia
Authors: Niskanen Eero , Phillips Steven L. , Hess Charles E.
Published: August 2010

11 patients with chronic neutropenia were evaluated. In 6 patients low numbers of CFU‐DG were observed. Only 3 of these patients also had low CFU‐C numbers, suggesting that these two precursors are not identical. Bone marrow samples from 2 patients were restudied a year later. The number of CFU‐DG remained low while CFU‐C numbers increased to control range in 1 patient. Studies for serum inhibitors were negative. No cytogenetic abnormalities were observed.

This study suggests that abnormalities at different levels in the haemopoietic precursor cell hierarchy can be detected either simultaneously or independently in patients with chronic neutropenia.
Demonstration of Histamine Receptors on Human Platelets by Flow Cytometry
Authors: Hallberg Torgny , Dohlsten Mikael , Baldetorp Bo
Published: August 2010

Fluoresceinated human albumin conjugated with histamine (FHA‐HIS) has been used for the demonstration of histamine receptors on human platelets. Such receptors were demonstrated on 40–63% of peripheral blood platelets in 4 healthy donors. The binding of FHA‐HIS was inhibited on 35–79% of the platelets by the histamine H1 receptor antagonists diphenhydramine and clemastine. The histamine H2 receptor antagonist cimetidine blocked the FHA‐HIS binding on 14–37% of the platelets. It is concluded that histamine H1 as well as H2 receptors occur on human platelets but the receptors are not equally distributed in the platelet population.
p69,71 Antigen Complex Detected by Monoclonal Antibody Leu 1 in the Identification of Particular Stages of Malignant B‐Cell Differentiation
Authors: Herrmann Friedhelm , Komischke Barbara , Ludwig Wolf‐Dieter , Sieber Gerhard , Rühl Hartmut , Langermann Hans‐Joachim
Published: August 2010

Lymphomatous cell samples from 86 patients with B‐cell neoplasia (34 chronic lymphocytic leukaemia, 8 hairy‐cell leukaemia, 5 prolymphocytic leukaemia, 20 immunocytic lymphoma, 9 centrocytic lymphoma, 3 centroblastic/centrocytic lymphoma, 3 lymphoblastic lymphoma, 1 plasma cell leukaemia and 3 plasmacytoma) were studied using the monoclonal antibody Leu 1, detecting a p69,71 antigen complex present on nearly all thymocytes, most (> 85%) peripheral T‐lymphocytes as well as some malignant B‐cells. Furthermore, we compared the reactivity of Leu 1‐positive B‐cells with those exhibiting conventional surface markers such as mouse‐erythrocyte‐receptor, FcIgG‐receptor, C3b‐ or C3d‐receptor and surface immunoglobulins of the various heavy‐ and light‐chain types.

Our results demonstrate a correlation between the expression of p69,71 antigen complex and distinct phenotypes revealed by conventional markers and underline the value of Leu 1 monoclonal antibody in the differential diagnosis of human B‐cell neoplasia.
Iron stores in chronic granulocytic leukaemia at presentation
Authors: CERVANTES FRANCISCO , ROZMAN CIRIL , BRUGUES ROSA , LLANAS INMACULADA
Published: August 2010

In 87 patients with Ph1 positive chronic granulocytic leukaemia (CGL), the bone marrow iron content was studied on smears obtained at diagnosis. A low sideroblast score and a decreased or absent marrow iron on semiquantitative estimation were found in 91 % and 85 % of cases, respectively. These findings did not correlate with blood parameters reflecting iron status such as Hb concentration, mean corpuscular volume, mean corpuscular haemoglobin, serum iron, total iron‐binding capacity and transferrin saturation, which were normal in most cases. In 30 patients, initial serum ferritin was estimated, normal or slightly increased levels being as a rule found. In 24 of such patients, serum ferritin was again measured in remission following busulphan and, although values remained normal, a significant decrease was observed with respect to the initial levels (P < 0.001). Thus, in spite of the consistent marrow pattern of iron depletion, initial iron stores appear to be normal in CGL. It seems, however, that the disease activity may partially influence the serum ferritin levels.
Refractory anaemia with excess of blasts terminating as Ph1 negative chronic myeloid leukaemia
Authors: ECONOMOPOULOS T. , PAPAGEORGIOU E. , HADJIOANNOU J.
Published: August 2010

A case of refractory anaemia with excess of blasts (RAEB) terminating with clinical and haematological picture of Ph1 negative chronic myeloid leukaemia (CML) is reported. It is suggested that the same abnormal clone of cells is responsible for the initial picture of the RAEB and the terminal CML picture.