bluuebunny/crossref_metadata_2025 huggingface dataset:
Relation between Life Expectancy and Composition of the Bone Marrow at Diagnosis of Chronic Myeloid Leukaemia
Authors: Sjögren U. , Brandt L. , Mitelman F.
Published: August 2010

The proportions of myeloblasts (MB), promyelocytes (PMC) and myelocytes (MC) within the granulopoietic precursor pool of the bone marrow and a mitotic index of the precursor cells were determined in 43 patients with chronic myeloid leukaemia (CML) diagnosed in the chronic phase of the disease. There was a negative correlation between the percentages of MB + PMC and the mitotic indices, i.e. large proportions of MB + PMC were associated with low mitotic indices. With increasing proportions of MB + PMC at diagnosis, survival was significantly reduced. Furthermore, only 22 % of patients with MB + PMC above the median value (28 %) associated with a mitotic index below the mean value (1.02 %) survived for more than 2 years whereas 82 % of the patients with a percentage of MB + PMC below the median value combined with a mitotic index above the mean value survived for more than 2 years. It is concluded that the composition and mitotic activity of the granulopoietic precursor pool at diagnosis of CML has a prognostic significance. Successive accumulation of early granulocytic precursors with a low mitotic activity probably occurs in the bone marrow during the chronic phase of CML ending up in the final blast crisis characterized by a heavy predominance of such celis.
The Effects of p Adrenergic Blockade on the Responses of Leucocyte Counts to Intravenous Epinephrine in Man
Authors: Gader A. M. A.
Published: August 2010

Changes in blood neutrophil and lymphocyte counts in response to a 30 min i.v. infusion of epinephrine alone and after pretreatment with propranolol (β‐blocking agent) were studied in 7 healthy subjects. Lymphocytes were classified into ‘normal’ and ‘stress' lymphocytes. Propranolol abolished the ‘stress' lymphocyte response to epinephrine but failed to block the ‘normal’ lymphocyte and, in the majority of subjects, the neutrophil responses. This was taken to indicate that the ‘stress' lymphocyte response is β‐adrenergic in type. A working hypothesis which involves both α and β‐receptors separately was suggested for the ‘normal’ lymphocyte response. More work is needed to clarify the nature of neutrophil responses.
Factor VIII Antigen in the Vessel Walls in Von Willebrand's Disease and Haemophilia A
Authors: Holmberg L. , Mannucci P. M. , Turesson I. , Ruggeri Z. M. , Nilsson I. M.
Published: August 2010

Biopsy specimens of superficial veins were obtained from 5 patients with von Willebrand's disease and 3 patients with haemophilia A and studied for factor VIII antigen with the aid of a direct immunofluorescent technique. 15 healthy men served as controls. In all the controls a bright specific fluorescence was observed in the intimal layer of the vein, but 3 patients with severe von Willebrand's c'isease lacked the antigenic protein in the intima. The fluorescence was, however, present in one patient with moderately severe von Willebrand's disease and in one patient with an atypical form of the disease, as well as in 3 with classical haemophilia. When protein was found in the vessel wall it was always demonstrable also in the plasma and vice versa. It is assumed that the von Willebrand factor ‐ factor VIII protein exerts an effect on primary haemostasis also locally in the vessel wall.
Kinetics of Rat Bone Marrow Cells Cultured in Diffusion Chambers: Effect of Heterologous Implantation and Irradiation of the Host
Authors: Petersen B. Heier , Meyer T. , Tjernshaugen H.
Published: August 2010

Rat bone marrow cells were cultured in diffusion chambers implanted into the peritoneal cavities of normal or irradiated rats and mice.

After implantation into normal rats there was an exponential growth of the macrophages (Td, 24 h), and a steady‐state equilibrium of granulopoiesis. In normal mice the macrophage growth was almost identical with that occurring in normal rat hosts, but the rat granulocytes were stimulated to improved growth compared to rat hosts. In preirradiated hosts (650 R) the granulopoiesis was still more enhanced (Td 58 h in rats versus 20 h in mice). The macrophages were stimulated by pre‐irradiation, but not to the same extent as granulocytes (Td 15.2 h in mice, and 12.4 h in rat hosts). The ‘effective’ progenitor cell concentration increased from 3.1 in normal rats to 14.1/105 bone marrow cells in preirradiated hosts, as measured with limiting dilution technique.

The sensitivity of rat cells to environment indicates that rat cell culture may be convenient for studying the effect of long range factors on haematopoiesis.
Preleukaemic Abnormal Myelopoiesis Induced by Chlorambucil: A Case Study
Authors: Tulliez M. , Ricard M. F. , Jan F. , Sultan C.
Published: August 2010

The authors report a patient treated for 3 years with chlorambucil for scleroderma. This apparently produced a preleukaemic sideroblastic anaemia and acute leukemia. This point out the consequences of the employment of immunodepressive agents.
Platelet Factor 4 (PF‐4) An Electroimmuno Assay for PF‐4 in Human Plasma
Authors: Gjesdal Knut
Published: August 2010

An immunological method for the quantitation of platelet factor 4 (PF‐4) in human plasma and serum is reported. Purified human platelet factor 4 was used to raise specific antibodies in rabbits. The antibodies were used in an electroimmuno assay. In platelet‐poor plasma, PF‐4 levels were too low for direct estimation by this method. The samples were consequently concentrated and partially purified by absorption to Sepharme‐heparin followed by elution using a small volume of concentrated heparin solution. The PF‐4 values obtained by electroimmuno assay of such eluates were in good agreement (p < 0.01) with assay values from a heparin‐thrombin time system.
Polymorphonuclear Leucocyte Chemotaxis in Boyden Chambers Effect of Low Concentrations of Vinblastine
Authors: Bandmann Ulf , Norberg Bo , Rydgren Lars
Published: August 2010

It has been reported by previous authors that vinblastine in high and presumably non‐specific concentrations (10‐5‐10‐4 M) inhibits polymorphonuclear (PMN) chemotaxis in vitro. In the present study, vinblastine in subantimitotic concentration (10‐8M) induced maximal inhibition of PMN chemotaxis in a modified Boyden chamber. It is suggested that the vinblastine inhibition of PMN chemotaxis is due to an interference with the spatial reorganization of centriole‐associated microtubules during PMN direction‐finding or PMN directional movement. The effect of subantimitotic concentrations of vinblastine and other antitubulins on PMN chemotaxis may have important applications in the treatment of diseases in which the tissue damage is mediated by the polymorphonuclear leucocytes.
Platelet Aggregation and Haemolysis Induced in Rats by Intravenous Infusion of ADP ‐Effect of Potentially Antithrombotic Drugs
Authors: Innocenti I. Reyers‐Degli , Poggi A. , Gaetano G. de
Published: August 2010

This paper describes a simple experimental model to quantitate the in vivo aggregation of rat platelets induced by ADP and the in vivo effectiveness of compounds with potential anti‐aggregating activity; only drugs known to inhibit in vitro the first phases of platelet aggregation (PGE1, pyrimido‐pyrimidine compounds) were inhibitory in this model; in contrast, acetylsalicylic acid, known to inhibit in vitro the last phases of platelet aggregation, was ineffective; no interaction between pyrimido‐pyrimidine compounds and acetylsalicylic acid was observed. Besides platelet aggregation, ADP also induced a marked haemolysis; the latter was not inhibited by any of the drugs tested.
Familial Leukaemia: A Study of 909 Families
Authors: Gunz F. W. , Gunz J. P. , Chapman C. J. , Houston I. B.
Published: August 2010

A family survey was conducted among 909 patients with leukaemia of all types, with the purpose of establishing the incidence of further cases of leukaemia among relatives.

Among a total of 41,807 relatives 8,349 were deceased, and the cause of death was objectively confirmed in 5,011.

72 patients had one or more relatives with leukaemia. First degree relatives with leukaemia were much more frequent in families of patients with chronic lymphocytic than in those of patients with chronic granulocytic leukaemia.

The incidence of leukaemia among first degree relatives was established to be 2.8‐3.0 times, among more distant relatives about 2.3 times, and overall about 2.5 times that expected. This excess is of the order of that observed in relatives of patients with certain solid tumors.

Genetic factors may have accounted for much of the excess incidence in chronic lymphocytic and acute leukaemia, but there was little evidence for a genetic background in chronic granulocytic leukaemia.

With the possible exception of one family with muitiple cases, a simple Mendelian mechanism did not appear to be involved in the leukaemia families investigated. It appeared more likely that a polygenic mechanism led to a heightened susceptibility to the disease in these families.
Congenital Dyserythropoietic Anaemia with Features of Both Type I and Type II
Authors: Seip Martin , Skrede Sverre , Bjerve Kristian S. , Hovig Torstein , Gaarder Per Ivar
Published: August 2010

A 13 year old girl with the typical clinical and haematological picture of congenital dyserythropoietic anaemia (CDA) is reported. The bone marrow is highly cellular with 70 per cent erythroid cells, and 28% bi‐ and multinuclear cells among the orthochromatic and polychromatic erythroblasts. Moderate megaloblastoid changes are present. On light microscopy the findings are in agreement with those described in CDA type II. On electron microscopy both the cytoplasmatic changes described as typical of CDA type II, and the nuclear changes found in type I can be demonstrated. The acidified serum test (Ham test) is negative with normal sera. The patient's red blood cells show increased agglutinability with anti‐I and anti‐i antibodies, but no haemolysis. Total serum lipids are about 50% of the normal average. All lipoprotein classes are lowered to about the same extent. The total phospholipid content of the erythrocytes is slightly reduced, with a moderate, relative increase of the lecithin fraction and a decrease of the sphingomyelin fraction.

Doubts can be raised about the tenability of the current classification of CDA based on morphological and serological criteria, especially about the distinction between types I and II.
Haemolytic Anaemia with Hereditary Pyruvate Kinase Instability Developing Acute Leukaemia
Authors: Goebel K. M. , Goebel F. D. , Janzen R. , Kaffarnik H.
Published: August 2010

The case of a 27‐year‐old woman with pancytopenia, revealing acute monocytic leukaemia and haemolytic anaemia, is described in detail. The underlying cause for the red cell destruction was found to be a pyruvate kinase (PK) instability. Further investigation into three generations of her family (n = 12) disclosed a hereditary PK instability. This was proven by performing biochemical studies to elucidate mutants representing a structurally defective enzyme. Since conversions of pancytopenia with acquired red cell enzyme deficiency into leukaemia have been described, our observation emphasizes that hereditary red cell enzymopathy might also be associated with adult acute leukaemia.
A Circulating Factor V Inhibitor: Possible Side Effect of Treatment with Streptomycin
Authors: Stenbjerg S. , Husted S. , Mygind K.
Published: August 2010

A potent inhibitor of factor V was discovered in a middle aged woman shortly after streptomycin therapy. The patient suffered from severe bleeding over a period of 10 days and the inhibitor was demonstrable for 6 weeks. By use of specific antisera the anticoagulant was found to be of an IgG nature. In agar electrophoresis the inhibitor mowed with the immunoglobulin fraction and was separable from factor V activity in the pathological plasma although no factor V activity was demonstrable in untreated patient plasma. It is suggested that this method should be used to distinguish between cases of inhibitors in patients with congenital factor V deficiency and cases of transient inhibitors in patients with normal factor V production.
Selective Eradication of Rat Bone Marrow Erythroid Cells by Administration of Cytosine Arabinoside
Authors: Ben‐Ishay Zina
Published: August 2010

The in vivo effect of a single i.p. injection of cytosine arabinoside (250 mg/kg body weight) on the rat bone marrow is reported. Cytosine arabinoside (ara‐C), a potent inhibitor of DNA‐synthesis, was seen to produce selective necrosis of fast cycling bone marrow erythroblasts. The depleted erythroid marrow is replenished by stem cells which are members of the lymphoid‐transitional cells compartment. An indirect correlation between the degree of erythroid cell depletion and the extent of marrow lymphocytosis was noted 6–12 h after the administration of ara‐C. At 24–48 h, however, the marrow returned to its normal activity.

The rat bone marrow 6–12 h following a single injection of ara‐C is suggested as an experimental model for providing stem cells committed to the erythroid line.
Immunosuppressive Treatment in Haemophiliacs with Inhibitors to Factor VIII and Factor IX
Authors: Nilsson Inga Marie , Hedner Ulla
Published: August 2010

9 patients with severe haemophilia A and inhibitors (inhibitor levels between 0.1 to 5.8 U/ml) and 3 patients with severe haemophilia B and inhibitors (inhibitor levels between 0.1 to 11 U/ml) were treated on a total of 16 and 13 occasions, respectively, with a large dose of antigen (factor VIII or factor IX) and cyclophosphamide (10–15 mg/kg b.w. i.v. initially and then 2–3 mg/kg b.w. orally for 7–10 days) in connection with severe bleeding and surgery. All the patients had proved not to respond to treatment with factor VIII or factor IX concentrate alone, and all except one had shown strong secondary antibody increases. In 6 of the patients with haemophilia A the treatment (11 occasions) had a satisfactory haemostatic effect and even permitted neurosurgery without bleeding complications. The inhibitor level remained at zero for 5–10 days, after which it gradually began to return towards its original level. In these cases it was possible to give factor VIII in amounts which neutralised the inhibitor and afterwards raised the factor VIII initially to at least 50%.

In the 3 patients with haemophilia B treatment (13 occasions) was successful except on one occasion, and surgery was performed without abnormal bleeding. The factor IX level was initially raised to at least 50% except in the one failure. The inhibitor level remained at zero for 12 days to 3 months, after which it gradually rose towards its original level. One patient was treated on 8 occasions.
Coagulation Profile and the Ethanol Gelation Test with Special Reference to Components Consumed during Coagulation
Authors: Slaastad R. A. , Godal H. C.
Published: August 2010

In 753 consequtive blood samples (from the same number of patients) routinely examined for coagulation abnormalities, a positive ethanol gelation test was found in 160. In 7 samples with plasma fibrinogen below 150 mg/100 ml and a positive test, other laboratory signs of consumption coagulopathy (low thrombocyte count, low factor V, low antithrombin III, large amounts of FDP in serum and great discrepancies between Normotest and Thrombotest) were regularly observed. Also at normal or high fibrinogen levels, a positive ethanol gelation test was more frequently associated with low thrornbocyte counts, low factor V and Normotest/Thrombotest discrepancy than was a negative test. In 46 % of the samples with a positive test, fibrinogen was higher than 500 mg/100 ml (versus 4 % in those with a negative test). In one‐third of these samples, all other parameters gave normal results.
Foamy Histiocytosis of the Spleen in Patients with Chronic Thrombocytopenia
Authors: Cohn Jørgen , Tygstrup Inge
Published: August 2010

In 17 of the 64 spleens removed from patients with chronic thrombocytopenia lipid‐laden histiocytotes were demonstrated. No correlation was found between these pathological findings and the age of the patients at diagnosis or splenectomy, the duration before splenectomy of therapy with glucocorticoids, the period with thrombocytopenia or the platelet count. 7 of the patients, who relapsed after splenectomy had lipid‐laden histiocytes in their spleens i.e. 58 % of the patients with relapse, compared with 10 patients with foamy histiocytosis and without relapse i.e. 19 % of the patients without relapse. At follow up, 3 of the 17 patients with splenic histiocytosis still had thrombocytopenia, compared with 1 of the 47 patients without foamy cells. Foamy histiocytosis of the spleen from a patient with chronic thrombocytopenia may indicate a dubious prognosis.
The Content of Erythrocyte 2,3 Diphosphoglycerate and Adenosine‐5‘‐Triphosphate in Myelomatosis and Leukaemia
Authors: Hjelm Magnus , Udén Ann Mari , Engstedt Lars
Published: August 2010

Ery‐DPG and thus the oxygen‐releasing capacity of haemoglobin increases in myelomatosis and in chronic myelocytic and lymphocytic leukaemia at decreased concentrations of haemoglobin, to the same extent as in other types of anaemia. Consequently the need for blood transfusions is less than assumed in these disorders. Ery‐ATP is considerably increased in chronic myelocytic leukaemia, the values correlating positively with the ‘activity’ of the disease. This finding can probably be used for diagnostic and prognostic purposes.
Monoclonal B‐Lymphocytes in Peripheral Blood of Patients with Plasma Cell Myeloma
Authors: Mellstedt Håkan , Pettersson Dagny , Holm Göran
Published: August 2010

Antisera were produced in rabbits against idiotypic determinants of the myeloma protein from 3 patients with IgG‐k myeloma. The antisera did neither cross‐react nor react with normal immunoglobulin (Ig). Idiotypic Ig‐structures were demonstrated by indirect immunofluorescence (IFL) on 70–94 % of peripheral B‐lymphocytes in untreated patients. The total numbers of circulating B‐lymphocytes were increased with a simultaneous decrease of T‐lymphocytes. Only one of the patients had blood lymphocytes which stained for cytoplasmic Ig with idiotypic antiserum.

The monoclonal lymphocyte population decreased gradually during treatment. Plasma cell counts in bone marrow, IgG concentration in serum and erythrocyte sedimentation rate decreased simultaneously, while the haemoglobin concentration increased. Very few monoclonal lymphocytes were present during remission. Later, the monoclonal lymphocyte population began to increase in 2 of the patients in parallel with clinical signs indicating relapse.

It is concluded that presence of monoclonal B‐lymphocytes indicates dissemination of the disease and that they may belong to the malignant cell clone.
Function of Granulocytes with Deficient Myeloperoxidase‐Mediated Iodination in a Patient with Generalized Pustular Psoriasis
Authors: Stendahl Olle , Lindgren Sören
Published: August 2010

The granulocytes of a patient with generalized pustular psoriasis (GPP) were found to have impaired ability to fix iodine after ingestion of yeast particles. Since hexose monophosphate shunt (HMS) activity was increased and the contents of 3 other lysmomal enzymes, β‐glucuronidase, N‐acetyl‐β‐glucosaminidase and lysoeyme were within normal range, the impaired iodination appeared to be due to a selective defect of myeloperoxidase (MPO) activity within the phagocytic cells. The deficient iodination was accompanied by a decreased intracellular killing of E. coli and C. albicans. Since hexose monophosphate shunt activity was enhanced and azide and cyanide inhibited the intracellular killing of E. coli only moderately, the patient's granulocytes may possess azide‐ and cyanide‐resistant, MPO‐independant microbicidal systems coupled to the oxidative metabolism. Assessment of granulocyte iodination and enzyme contents of the relatives of the patient revealed no hereditary transmission. Since GPF is characterized by the development of subcorneal pustules containing granulocytes, the MPO‐deficiency may be the cause of or enhance the development of the disease.
Erythroid Differentiation of Fetal, Newborn and Adult Haemopoietic Stem Cells
Authors: Rencricca N. J. , Howard D. , Kubanek B. , Stohlman F.
Published: August 2010

Erythroid regeneration was studied in lethally irradiated mice given transplants containing equivalent numbers of haemopoietic stem cells (i.e. CFU) from fetal liver, neonatal marrow or adult marrow. Adult marrow was taken from normal control mice, whose CFU for the most part were not in active cell cycle, as well as from phenylhydrazine‐treated groups whose CFU were in similar state of proliferation (i.e. ˜40–50% in DNA synthesis) as those derived from fetal liver and neonatal marrow. Splenic and femoral radioiron (59Fe) incorporation were measured at intervals after transplantation and were found to begin earliest in mice given fetal liver, then in animals given neonatal marrow and latest in recipients of adult marrow. Peripheral reticulocytes showed a similar pattern of recovery. The data reported herein suggest that the differences in erythroid regeneration evoked by transplants of fetal liver, neonatal marrow or adult marrow, are not solely attributed to the degree of proliferation in the pluripotential stem cell compartment. These data may, however, suggest a shorter doubling time for cells comprising the fetal and newborn committed erythroid compartments.
Testicular Function after Radiotherapy to Inverted ‘Y’ Field for Malignant Lymphoma
Authors: ASBJØRNSEN G. , MOLNE K. , KLEPP O. , AAKVAAG A.
Published: August 2010

Testicular function was estimated by sperm counts, hormone assays and recording of reported conceptions in 9 patients irradiated for malignant lymphoma. The treatment had been an inverted ‘Y’ field including the inguinal regions with, in addition, a mantle field in 8 patients.

Azoospermia or severe oligozoospermia was found in all but 1 patient, and the FSH levels were uniformly elevated. Testosterone and LH were within normal limits except in 2 patients with slightly subnormal testosterone levels.

7 of the patients were married to women of fertile age, and in 3 cases the wife became pregnant and gave birth to a healthy child. The time lapses from irradiation to conception were 18, 40 and 57 months. 2 of these patients had severe oligozoospermia on examination 2 and 4 months respectively from conception. Thus fertility may possibly be underestimated by sperm counting and hormone assays after this type of radiotherapy.
Platelet Function and Plasma Free Fatty Acids during Acute Myocardial Infarction and Severe Angina Pectoris
Authors: GJESDAL KNUT
Published: August 2010

The relationship between platelet function and plasma free fatty acid concentration has been studied serially during the initial 24 h in 11 patients suffering from acute myocardial infarction and in 5 patients with severe angina pectoris. Similar results were obtained in the 2 groups. Plasma free fatty acid concentration was initially high, and decreased significantly. The distribution of plasma free fatty acids remained unchanged. Platelet concentration was constant, whereas the percentage of reversible venous platelet aggregates initially was higher than in 11 healthy persons matched for age and sex. Platelet aggregates decreased transiently at 16 h. Venous reversible platelet aggregates correlated significantly with concentration of plasma free fatty acid, thus establishing a possible link between a change in lipid metabolism and platelet function. Plasma concentration of platelet factor 4 increased slightly but significantly during the initial hours. This may indicate an increased platelet release reaction.
Infusion of Human and Canine Factor VIII in Dogs with von Willebrand's Disease: Studies of the von Willebrand and Factor VIII Synthesis Stimulating Factors
Authors: BOUMA B. N. , DODDS W. JEAN , VAN MOURIK J. A. , SIXMA J. J. , WEBSTER W. P.
Published: August 2010

Dogs with von Willebrand's disease (VWD) were infused with a highly purified human and canine factor VIII preparation. Control infusions were performed using isotonic saline solution. Following all of the concentrate infusions, the bleeding times were shortened to within the normal range for up to 4 h. Factor VIII activity rose immediately after infusion, rapidly returned to preinfusion levels, and then increased again at 18 h. The levels of factor VIII‐related antigen (F VIII‐RA) as measured with anticanine factor VIII also increased after infusion and then gradually declined. There was no further increase in F VIII‐RA at 18 h, when the factor VIII activity showed the secondary increase characteristic of VWD. With antihuman factor VIII, two identifiable antigens were present in the plasma of the dogs given human factor VIII. The reduced platelet retention of these animals was not significantly altered following infusion, whereas ristocetin‐induced platelet aggregation was corrected in one of the dogs given human factor VIII. These studies indicate that factor VIII procoagulant and von Willebrand factor activities reside on a single molecule or form part of a molecular complex.

In addition, the factor VIII preparations appeared to contain the factor VIII synthesis‐stimulating factor and/or a precursor of factor VIII procoagulant activity.
Effects of Anticonvulsant Drugs on the Synthesis of DNA and Protein by Human Bone Marrow Cells in Vitro
Authors: WICKRAMASINGHE S. N. , SAUNDERS JUDITH , WILLIAMS GAIL
Published: August 2010

Suspensions of human bone marrow cells were incubated with various concentrations of phenobarbitone or phenytoin sodium for 2 h, and the effects of this incubation on the subsequent incorporation of 3H‐thymidine and 3H‐leucine into DNA and protein, respectively, were studied. Both drugs caused a depression of 3H‐thymidine incorporation and this phenomenon was not prevented by the addition of 100 μg of pteroylglutamic acid, folinic acid or 5‐methyltetrahydrofolate per ml of marrow culture. The lowest concentration of drug which caused a statistically significant depression of 3H‐thymidine incorporation was 200 μg per ml for phenobarbitone and 50 μg per ml for phenytoin sodium. Both phenobarbitone and phenytoin sodium also caused an increase in the incorporation of 3H‐leucine at concentrations of 50 and 20 μg per ml, respectively, suggesting the possibility that a stimulation of protein synthesis within erythropoietic cells may play an important role in the development of anticonvulsant‐induced macrocytosis.
Pernicious Anaemia and Lymphoproliferative Disease
Authors: Parker A. C. , Bennett M.
Published: August 2010

2 patients with associated lymphoproliferative disease and pernicious anaemia are described. The lymphocytes in each were characterized by surface marker studies. In 1 of the cases, therapy with vitamin B12 appeared to accelerate the neoplastic growth.
Familial Polycythaemia Vera
Authors: Manoharan A. , Garson O. Margaret
Published: August 2010

The familial occurrence of polycythaemia vera (PV) is rare, with only 3 authentic reports in the world literature.

This paper describes a family of 8 females, 3 of whom have PV and another has pernicious anaemia. Clinical and haematological data is presented to support the diagnosis of PV and exclude other causes of familial erythrocytosis. Cytogenetic studies were performed in 2 of the patients.
Blastic Transformation of Chronic Myelocytic Leukaemia Clinical Manifestations, Prognostic Factors and Results of Therapy
Authors: Pedersen‐Bjergaard Jens , Worm Anne‐Marie , Hainau Bo
Published: August 2010

24 patients with chronic myelocytic leukaemia (CML) have been followed closely during and after development of blastic transformation (BT). Severe fatigue in previously asymptomatic patients was the most frequently observed prodrome of transformation. Most significant clinical findings were anaemia, rapidly increasing WBC and increasing size of the spleen in patients with previously well‐controlled CML. 11 out of 24 patients responded to chemotherapy and had a median survival of 3 months, 6 obtained a complete remission (CR). Median survival time for all patients was 2 months from BT. Quality of life after BT was in most cases inferior. Thus, only 5 patients spent more than 1 month outside hospital.

Cytomorphological classification of blasts in marrow as granular or agranular showed no correlation to the results of chemotherapy or to survival.
Studies on an Iron‐poly (sorbitol‐gluconic acid) complex for Parenteral Treatment of Iron Deficiency Anaemia
Authors: DOMEIJ KRISTINA , HELLSTRÖM VERA , HÖGBERG KARL‐GUSTAV , LINDVALL SVEN , RYDELL GUNILLA , WICHMAN ULLA , ÖRTENGREN BÖRJE
Published: August 2010

A preparation containing an iron‐poly (sorbitol‐gluconic acid) complex for parenteral treatment of iron deficiency anaemia is described. The physical and chemical properties of the iron complex have been studied by using electrophoresis and gel permeation chromatography. A rapid absorption from the injection site after intramuscular administration to rabbits takes place, 70 per cent of the iron being absorbed after 24—48 hours. Thereafter, the absorption rate is slower, and 32 days after the injection 94 per cent has been absorbed from the injection site. In rabbits the maximum level of iron in serum is reached after 12—24 hours; in dogs after 1—3 hours. Disappearance from the serum takes place slowly. The complex is exclusively absorbed via the lymphatic route. Nine to ten per cent of the given dose is excreted by the kidney within 72 hours in rats and 24 hours in rabbits after intramuscular administration. On administration of the preparation to rats, made anaemic by phlebotomy, a rapid increase of haemoglobin values is observed as well as a very high utilization of the retained amount of the given dose.
Studies on the Effect of Parenteral Iron, Ferastral®, an Iron‐poly (sorbitol‐gluconic acid) complex, on Blood Coagulation in Man
Authors: PLOEM JAN E. , JEKEL MARIANNE
Published: August 2010

The possible influence of Ferastral®, an iron‐poly (sorbitol‐gluconic acid) complex, on blood coagulation in man was investigated.

Ferastral added to plasma produced no changes in blood coagulation until a final concentration of 2 000 μg/ml (35.8 mmol/l) was used, when minimal changes in blood coagulation factors were observed. Five patients were given an intramuscular injection of 250 mg Ferastral. No changes in blood coagulation and thrombocyte function were observed up to 5 hours after the initial iron injection.
The Absorption and Availability of Iron from Iron‐poly (sorbitol‐gluconic acid) complex in Rats as Measured by Phlebotomy
Authors: LINDVALL SVEN , RYDELL GUNILLA
Published: August 2010

The local and systemic availability of the iron in an iron‐poly (sorbitol‐gluconic acid) complex (Ferastral®) has been studied in rats. The animals were treated intramuscularly with the complex in a dose corresponding to 10 mg of iron per animal. The technique of repeated phlebotomy was used to induce and maintain constant levels of anaemia. The phlebotomies were started immediately after injection and at 14 and 28 days after dosing. At the end of the appropriate interval, the remaining amount of iron at the injection sites as well as the degree of utilization of the iron retained in the animals were estimated. It was shown that the amount of iron at the site of injection of these anaemic animals was less than 3% regardless of the time when the series of phlebotomies were started. It was also shown that the degree of utilization of the iron from the complex was 90% of the retained amount of iron when the phlebotomies immediately followed dosing, and 86% and 79% when initiated 14 days and 28 days respectively. The significance of the decrease in utilization is discussed.
Studies on the Placental Transfer in Rats of 59Fe‐ and 14C‐labelled Iron‐poly (sorbitol‐gluconic acid) complex
Authors: LINDVALL SVEN , DOMEIJ KRISTINA , GAGNER‐MILCHERT INGALILL , HELLSTRÖM VERA , RYDELL GUNILLA
Published: August 2010

The placental transfer of an iron‐poly (sorbitol‐gluconic acid) complex, Ferastral®, has been studied. By use of the 59Fe‐, 14C‐sorbitol, and 14C‐gluconic acid labelled complexes it was shown that the passage of the iron moiety is related to foetal need and that only negligible amounts of 14C from either 14C‐sorbitol or 14C‐gluconic acid labelled iron complexes were found in the foetus. This implies that the intact complex does not pass the placental barrier.
Iron‐poly (sorbitol‐gluconic acid) complex and Iron‐dextran in the Treatment of Severe Iron Deficiency Anaemia
Authors: Evers J. E. M.
Published: August 2010

An investigation has been carried out to study the efficacy of iron‐poly (sorbitol‐gluconic acid) complex (Ferastral®) in the treatment of iron deficiency anaemia. Ferastral was given by the intramuscular route every second or third day in a dose of 500 mg, divided in two injections. These were compared with the results of a group treated with iron‐dextran given by Total Dose Infusion (TDI). A total of 38 patients were treated with either Ferastral or iron‐dextran by TDI, respectively, given according to random allocation. The total dose of iron given in both groups was 1 500 mg of elemental iron.

The parameters investigated were haematocrit and haemoglobin. Side‐effects were also recorded. The results in the group treated with Ferastral where the mean initial haemoglobin value was 9.5 g/100 ml showed a mean haemoglobin increase to 13.2 g/100 ml after eight weeks. Initial haemoglobin values and haemoglobin increase for iron‐dextran by TDI were quite similar.

Three patients in the Ferastral group had transient discolouration at the site of injection and one patient in the iron‐dextran TDI‐group had a serious allergic reaction.
Ferastral® in the Treatment of Patients with Inflammatory Anaemia
Authors: Strandberg Olle , Wijnbladh Elisabeth
Published: August 2010

An investigation has been performed with a new parenteral iron preparation, iron‐poly (sorbitol‐gluconic acid) complex (Ferastral®) in the treatment with iron deficiency anaemia associated with inflammatory diseases, mainly rheumatoid arthritis. Fifteen moderately anaemic patients entered into the trial. These patients constituted a special group in whom the MCHCs were subnormal.

Observations were made concerning the occurrence of side‐effects. Particular attention was paid to those side‐effects which are known to be associated with the use of parenteral iron preparations in the treatment of rheumatoid subjects.

Ferastral was administered by intramuscular injection. The single doses given on any one occasion varied from a minimum of 100 mg to a maximum of 500 mg, divided into two separate injections.

The results of therapy, measured at eight weeks, showed significant increases in haemoglobin concentrations. Increases in erythrocyte count, MCHC and serum‐iron concentration were also found. There were no signs of acute toxic effects with Ferastral and in no patient was there exacerbation of arthritis as has been previously reported with iron‐dextran.
Treatment of Severe Iron‐deficiency Anaemia of Hookworm Infestation with Ferastral®, a new Intramuscular Iron Preparation
Authors: Ezem B. U. , Fleming A. F. , Werblińska B.
Published: August 2010

Thirty Nigerians with severe iron‐deficiency anaemia were treated with iron‐poly (sorbitol‐gluconic acid) complex (Ferastral®), which allows 500 mg iron to be given in one intramuscular injection. Two dose schedules were tried: A, eight patients received Ferastral 5 ml (250 mg iron) and B, 22 patients 10 ml (500 mg iron) on alternate days. Supportive treatment included prophylactic antimalarials and folic acid supplements for three weeks. Initial haemoglobin (Hb)‐concentrations were 1.7–7.6 g/100 ml; total dose of iron required was 1 496–3 500 mg.

No patient complained of undue pain at injection site or other side‐effects. There was no evidence of hepatic or renal toxicity after four weeks in 18 patients and eight weeks in 11 patients.

Average daily Hb‐regeneration in the first two weeks on schedule A was 0.26 g/100 ml and schedule B 0.33 g/100 ml. Mean daily regeneration in patients with initial Hb < 3.6 g/100 ml was 0.30 g/100 ml, while in those with Hb > 5.5 g/100 ml it was 0.25 g/100 ml. All haematological indices returned to normal by eight weeks, except in three patients with minimally reduced MCH and three other patients in whom there was persistent anaemia due to blood loss, only one of whom was again sideropenic. Bephenium hydroxynaphthoate was found to be ineffective and tetrachloroethylene highly effective in the treatment of hookworm.

Ease of administration, lack of side reactions and effectiveness of Ferastral represent a therapeutic advance of value in rural tropical areas.
Serum Myeloperoxidase and Lactoferrin in Neutropenia
Authors: Olofsson Tor , Olsson Inge , Venge Per , Elgefors Börje
Published: August 2010

Radioimmunosorbent assays for determination of serum content of the neutrophil proteins myeloperoxidase and lactoferrin are described. Serial studies were performed in patients with neutropenia. In 2 cases of cyclic neutropenia the myeloperoxidase level showed slight variations within the normal range during the cycle while lactoferrin displayed a clear correlation with neutrophil counts. In 1 case with persistent agranulocytosis myeloperoxidase was normal but lactoferrin was extremely low. During the regeneration phase of drug‐induced neutropenia neutrophil counts and serum lactoferrin increased in a parallel fashion. Since serum myeloperoxidase was normal during profounded neutropenia it is suggested to derive primarily from myeloperoxidase‐rich granulopoietic precursor cells of the marrow. Serum lactoferrin on the other hand seems to derive from leakage of more mature granulopoietic cells of blood and marrow. Studies of neutrophil proteins of serum may aid in evaluation of neutropenic patients.
Basophilic Differentiation of Chronic Myelogenous Leukaemia Cells in Vitro
Authors: Miyoshi I. , Uchida H. , Tsubota T. , Kubonishi I. , Hiraki S. , Kitajima K.
Published: August 2010

Peripheral leucocytes from 10 patients with chronic myelogenous leukaemia (CML) were cultured in liquid medium and observed morphologically for 6 to 10 weeks. All cultures showed an increased proportion of mature basophils at about 3 weeks and most cultures consisted predominantly of mature basophils at about 5 weeks. The results indicate preferential basophilic differentiation of CML leucocytes in vitro and are consistent with basophilia frequently observed in CML patients.
Anorexia Nervosa and Polymorphonuclear (PMN) Granulocyte Reactions
Authors: Palmblad Jan , Fohlin Lars , Lundstrom Maj
Published: August 2010

10 patients with anorexia nervosa were compared with controls with normal weight, regarding their peripheral blood polymorphonuclear (PMN) granulocyte reactions. The anorexia patients showed a statistically significant decrease in PMN bactericidal capacity and PMN adherence. The mean chemotaxis did not differ, but in two of the anorexia patients chemotaxis was almost absent. The intracellular activity of alkaline phosphatase was below the reference values in 5 of the 6 patients in whom it was investigated. ‐ It is concluded that changes in granulocyte function may be noted in anorexia nervosa, but their clinical significance is uncertain, as no patients had recurrent or severe infectious diseases.
Studies on Human Preleukaemia
Authors: Hast Robert , Reizenstein Peter , Jores Sylvia
Published: August 2010

In 34 patients with aregenerative anaemia and hypercellular bone marrow, a condition earlier suggested to be of a preleukaemic nature, erythroblast thymidine labelling indices (LI) were significantly decreased, as would be expected in preleukaemia. The 59Fe erythrocyte incorporation after 2 weeks was generally low. The 59Fe plasma clearance was fast in 22 of 31 patients, normal in 5 and moderately prolonged in 4.

These 4 patients had a low relative number of erythroblasts in the marrow. A significant relationship between the marrow erythroblast number and the 59Fe plasma clearance could be demonstrated.

Cases with an increased number of myeloblasts in the marrow did not differ significantly from the rest in LI and iron incorporation.
Kinetics of Erythropoiesis in the Liver Induced in Adult Mice by Phenylhydrazine
Authors: Ploemacher R. E. , van Soest P. L. , Vos O.
Published: August 2010

Phenylhydrazine treatment of normal mice elicited a rise in the numbers of CFU‐S in blood, spleen and liver. High numbers of CFU‐S were found in blood and liver 4 d after the first phenylhydrazine injection. CFU‐S in the liver decreased slowly and were absent after 2 weeks. Blood CFU‐S returned to normal levels by day 6, whereas spleen CFU‐S numbers remained high upto day 12 with a 20‐fold increase being apparent between days 5 and 8. Bone marrow CFU‐S numbers were relatively unaffected except for a dip between days 4 and 7 with a nadir at day 5 where numbers decreased to 50 % of the control levels.

Approximately 40 % of liver, spleen and blood CFU‐S, present on the 4th d after initiation of phenylhydrazine treatment, were killed with a single dose of hydroxyurea whereas bone marrow CFU‐S numbers were not significantly reduced by the drug. Splenectomy performed before (21 d) or during phenylhydrazine treatment did not diminish the number of CFU‐S found in the liver on day 4. A 3 d interval was observed between peak numbers of CFS‐U and erythroblasts in the liver which suggests that hepatic CFU‐S are able to undergo differentiation along the erythroid pathway. The presence of macrophages was correlated with that of erythroblasts in the hepatic central veins. These macrophages may be essential to the liver environment for induction of erythropoiesis.
Studies on the Regeneration of the CFU‐C Population in Blood and Bone Marrow of Lethally Irradiated Dogs after Autologous Transfusion of Cryopreserved Mononuclear Blood Cells
Authors: Nothdurft Wllhelm , Bruch Christian , Fliedner Theodor M. , Ruber Esther
Published: August 2010

In a group of 8 lethally irradiated (1200 R) dogs, that were transfused autologously with cryopreserved mononuclear cells (MNC) derived from the peripheral blood by leucapheresis the concentration of colony‐forming units in agar (CFU‐C) in bone marrow and peripheral blood was estimated at regular intervals after irradiation and transfusion of MNC. The numbers of MNC transfused per kg body weight ranged from 0.32 times 109 to 1.63 times 109 with an incidence of CFU‐C between 0.02 times 105 and 1.38 times 105. In 6 dogs the CFU‐C levels in the bone marrow reached the normal pre‐irradiation values between days 15 and 20. But in 2 dogs that had received the lowest CFU‐C numbers the regeneration of the bone marrow CFU‐C was markedly delayed. In general the time course of the bone marrow repopulation by CFU‐C for single dogs was reflected by a corresponding regeneration pattern of the blood CFU‐C. The time course of the curves for the blood CFU‐C levels on the other hand was of the same kind as for the granulocyte values in the peripheral blood, that reached the normal levels mainly around day 30 and thereafter. Considerable fluctuations were seen in the blood CFU‐C levels of single dogs before irradiation and after mononuclear leucocyte transfusion. Despite of such limitations the blood CFU‐C content appeared to be a useful indicator of haematopoietic regeneration of the bone marrow.
Prognostic Factors in Hodgkin's Disease
Authors: Björkholm M. , Holm G. , Mellstedt H. , Johanssno B. , Askergren J. , Söderberg G.
Published: August 2010

An unselected material of 83 consecutive and previously untreated adult patients with Hodgkin's disease (HD) from the Stockholm area is presented. The distribution of patients according to age was characteristically bimodal. The histopathological subtypes were 16 % lymphocyte predominance (LP), 33 % nodular sclerosis (NS), 37 % mixed cellularity (MC) and 11 % lymphocyte depletion (LD). The patients were treated with aggressive megavoltage irradiation and multidrug chemotherapy. Major factors affecting prognosis were age, clinical stage and constitutional symptoms. Patients with LP and NS subtypes had only slightly better prognosis than patients classified as MC and LD. The overall survival was 68 % at 4½ years, which is close to that reported from other groups with similar composition of their materials with regard to age, histopathology and stage.
Serum Cholesterol and Triglycerides in Children with Anaemia
Authors: Seip Martin , Skrede Sverre
Published: August 2010

Serum cholesterol and triglyceride levels were determined in 17 children with various forms of anaemia and varying rates of red cell production. Anaemic patients had low serum cholesterol values, and a good correlation between Hb and serum cholesterol levels was found. The serum triglyceride levels were also low in most patients, but the results were less closely related to Hb. No relationship could be demonstrated between the rate of red cell production as judged by retieulocyte counts, and serum cholesterol or triglycerides. Apparently all lipoprotein classes are reduced in individuals with uncomplicated anaemias. This hypolipidaemia can only partly be explained by the diluting effect of the increase in plasma volume accompanying anaemia.
Erythropoiesis in the Anaemia of Chronic Disease
Authors: Cavill I. , Ricketts C. , Napier J. A. F.
Published: August 2010

The amount and effectiveness of erythropoiesis was measured using 59Fe in 10 patients with the anaemia of chronic disease and in 10 iron deficient patients with a comparable degree of anaemia. In both conditions the anaemia was the result of the failure of the marrow to compensate for a modest degree of peripheral haemolysis but ineffective erythropoiesis was significantly greater in iron deficiency than in chronic disease. The results suggest that although the peripheral blood picture is similar in both conditions the anaemia of chronic disease cannot be attributed simply to iron deficient erythropoiesis.
Factor IX and thrombosis
Authors: Aledort L. M.
Published: August 2010

Fractionation technology has made Factor IX concentrates available. In addition to a very high incidence of hepatitis, thrombosis is being recognized as a consequence of their use. Contradictory reports exist in the literature as to the incidence of thrombotic events. A recent study of thrombohemorrhagic phenomena after infusion with Factor IX concentrates in patients with congenital Factor IX deficiency (hemophilia B) or liver disease, revealed an incidence of twenty episodes in 188 cases (11 %). It is imperative to delineate the thrombo‐genic factors and find methods for their removal to insure the safety of Factor IX products.
Myeloperoxidase and Lactoferrin of Blood Neutrophils and Plasma in Chronic Granulocytic Leukaemia
Authors: Olofsson Tor , Olsson Inge , Venge Per
Published: August 2010

Myeloperoxidase, restricted to primary granules, and lactoferrin, restricted to secondary granules, were determined in plasma and neutrophils of peripheral blood in chronic granulocytic leukaemia (CGL). Plasma myeloperoxidase was increased 2–3 times while plasma lactoferrin increased 2–8 times. This discrepancy indicates different modes of release or elimination. A correlation was found between the leucocyte count and plasma myeloperoxidase or lactoferrin. A correlation was also found between cellular and plasma levels of lactoferrin but not for myeloperoxidase indicating the source for plasma lactoferrin to be circulating leucocytes, which may not be the case for plasma myeloperoxidase. Decreased neutrophil lactoferrin was found in 71% of the CGL cases while myeloperoxidase was decreased in 18 %. Serial studies on individual CGL subjects showed low cellular lactoferrin during phases with rapidly expanding leucocytosis indicating defective maturation of neutrophils or abnormal release because of prolonged intravascular life‐span.