bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Lymphocytic Leukaemia of T Cell Origin
Authors: Geisler C. , Ralfkiær E. , Astrup L. , Christensen I. , Dickmeiss E. , Hansen M. Mørk , Larsen J. K. , Petersen J. , Plesner T.
Published: August 2010

Based on the literature and 2 patients studied, we suggest that at least 2 different clinical entities are included in the concept of T CLL: (i) a clinical variant characterized by a relatively benign course, splenomegaly without lymphadenopathy, low lymphocyte count and granulocytopenia; the proliferating lymphocyte is morphologically mature, of medium size and a cytoplasm with azurophilic granules staining positively for acid phosphatase and corresponding to parallel tubular arrays as demonstrated by electron microscopy. The cells form E‐rosettes, have no surface‐membrane‐bound Ig, but Fc‐receptors for IgG. With monoclonal antibodies, the phenotype is OKT3+, OKT4‐ and OKT8+, theoretically corresponding to the suppressor/cytotoxic T lymphocyte subset, but functionally the cells demonstrate killer cell (responsible for ADCC), but not natural or suppressor cell activity. (ii) another clinical variant with an aggressive course, massive hepato‐splenomegaly, lymph node enlargement and very high lymphocyte counts; the lymphocytes are small without cytoplasmic granules; their immunological and functional characteristics have not been determined, but morphologically the cells correspond to the T helper/inducer lymphocyte subset. Thus, involvement of different T lymphocyte subsets may be the reason for the clinical variation in T CLL.
Erythrocyte Pyrimidine 5‘‐Nucleotidase Deficiency
Authors: Hansen Thor Willy Ruud , Seip Martin , de Verdier Carl‐Henric , Ericson ÅKe
Published: August 2010

We present 2 Norwegian siblings who we believe to be the first cases of pyrimidine 5′‐nucleotidase deficiency diagnosed in the Scandinavian countries. In addition to the features presented by previously published cases, our patients exhibited signs of intravascular haemolysis with haemoglobinuria and increased loss of iron in the urine. The loss of iron has made iron medication necessary from time to time. A kidney biopsy from the oldest patient revealed accumulation of iron in the epithelium of the proximal tubuli. The kidneys were considerably enlarged in both patients, but with normal function tests.
The Influence of Citrate on Platelet Aggregation and Malondialdehyde Production
Authors: Huijgens P. C. , van den Berg C. A. M. , Voetdijk A. M. H. , Imandt L. M. F. M.
Published: August 2010

3 commonly used parameters for platelet aggregability were tested for their dependence on citrate concentrations. Relatively minor changes in citrate concentrations markedly influenced ADP threshold values for secondary aggregation. Collagen induced platelet malondialdehyde (MDA) production was reduced by increasing the citrate level. This effect was still present in plasma which was also anticoagulated with EDTA. Thrombin induced MDA production was considerably higher in EDTA than in citrate plasma. Citrate appears to inhibit aggregation as well as MDA synthesis. The latter effect does not seem to be solely caused by the effect of citrate on ionized calcium levels.
Regulation of Cobalamin and Folate Metabolism by Methionine in Human Bone Marrow Cultures
Authors: Sourial N. A. , Brown L.
Published: August 2010

In cobalamin deficiency folate metabolism is disturbed. In the liver this deranged metabolism can be overcome by methionine, however, methionine failed to overcome this abnormality in bone marrow cultures from cobalamin deficient patients. In cobalamin deficient E. coli mutant bacteria, methionine under different conditions could either inhibit or potentiate the growth of the organism. This study was therefore initiated to test the effect of methionine, under different conditions, on bone marrow cultures.

The defective DNA synthesis in megaloblastic bone marrow due to cobalamin deficiency could be corrected by the in vitro addition of low 0.27 μmol (40 μg) but not high 6.7 μmol (1 mg) amounts of methionine. This was measured by the ability of deoxyuridine to suppress the 3H‐thymidine incorporation into DNA.

The effect of methionine in facilitating de novo DNA synthesis is probably due to the catalytic action of SAM which activates cobalamin dependent methyltransferase enzyme thus potentiating the effect of cobalamin. In contrast high concentrations of methionine may inhibit this enzyme.
Granulopoiesis in the Neutropenia of Negroes
Authors: O'Brien H. A. W. , Horton M. A.
Published: August 2010

A number of reports have shown that the peripheral blood neutrophil count in many negroes is considerably lower than in white populations. This neutropenia has been ascribed previously to both genetic and nutritional causes. We have studied bone marrow reserve function and myelopoiesis in 3 negroes with neutropenia, and found these to be normal.
Haemostatic Effect of Prednisolone in Thrombocytopenia
Authors: Freund Leif Gade , Berild Dag , Hainau Bo
Published: August 2010

In a short‐time study, 8 patients with thrombocytopenia and clinical signs of bleeding were experimentally treated with prednisolone as the only therapeutic measure to control the bleeding tendency. 2 patients had idiopathic thrombocytopenic purpura and 6 acute non‐lymphocytic leukaemia. 1 of the leukaemic patients was thrombocytopenic on admission. 5 had thrombocytopenia due to antileukaemic chemotherapy. The capillary fragility test, evaluated blindly, and bleeding time determination were performed just before treatment and repeated once after 2–4 d of treatment. Platelet counts were carried out simultaneously. Capillary resistance, determined by the capillary fragility test, improved greatly during the administration of prednisolone, irrespective of the platelet count, and no serious bleeding occurred. The bleeding time remained prolonged.
The Effect of Histamine H2 Receptor Antagonists on Platelet Aggregation in Man
Authors: Horton Michael A. , Amos Roger J. , Jones Richard J.
Published: August 2010

The in vivo and in vitro effects on the aggregatory response of human platelets to ADP and collagen of a series of imidazole and non‐imidazole histamine H2 receptor antagonists, and imidazole derivatives, have been studied. Bolus i.v. administration of the antagonists cimetidine and oxmetidine was without effect. However, inhibition of platelet aggregation was observed in vitro with oxmetidine, metiamide and to a lesser extent burimamide, but not with cimetidine or the non‐imidazole antagonist ranitidine. Of the imidazole derivatives only imidazole and its 1‐methyl analogue significantly affected platelet aggregation. The relationship between potency as a histamine H2 receptor antagonist, the presence of an imidazole ring structure and the antiaggregatory effectiveness of these compounds is discussed. Although certain antagonists clearly inhibit platelet aggregation in vitro, effects are only seen at drug concentrations exceeding those achieved under normal therapeutic conditions; thus the clinical significance of these observations remains to be determined.
Prognostic Value of Serum Lactic Dehydrogenase in Non‐Hodgkin's Lymphoma
Authors: Hagberg H. , Siegbahn A.
Published: August 2010

Lactic acid dehydrogenase (LDH) is a glycolytic enzyme that may be elevated in the serum of patients with non‐Hodgkin's lymphoma (NHL). In this investigation LDH was assayed in sera from 155 untreated patients with NHL. Serum LDH (S‐LDH) was found to be significantly correlated both to the spread of the disease and to the histological grade of malignancy i.e. more advanced disease or more aggressive histopathology was associated with higher S‐LDH values. A high pretreatment S‐LDH level (> 8.0 μkat/l) in stages III and IV correlated significantly to a decreased survival time. The patients with a pretreatment level of < 8.0 μkat/l had an actuarial 2‐year survival of 80%, compared to 30% in the patients with levels > 8.0 μkat/l (P < 0.001). In stages I and II all 6 patients with a high pretreatment level (> 8.0 μkat/l) relapsed during or a short time after radiotherapy. In a longitudinal study of 24 patients it was found that S‐LDH reflected in the clinical course. In patients treated to partial or complete remission, S‐LDH decreased and at relapse it rose again. It is concluded that S‐LDH might be useful both as a prognostic marker and to monitor the course of the disease.
Solitary plasmacytomas of bone
Authors: KVALØY STEIN , LANDAAS TONE ØSTBERG , ABRAHAMSEN ARNE FOSS , LANGHOLM RUTH , MARTON PER F.
Published: August 2010

Sixteen patients with solitary plasmacytomas of bone (SPB) have been reviewed with regard to prognosis, response to treatment, and protein findings.

Three patients developed multiple myeloma (MM), and 2 of the patients died due to dissemination. Local recurrence was not seen. Moreover, this study confirms other reports as for the good prognosis of SPB.

Intracytoplasmatic immunoglobulin (Ig) has been characterized in tumour tissue from 10 cases by the peroxidase‐anti‐peroxidase (PAP) method. The tumour tissue stained positively with monoclonal Ig in 8 out of 10 cases. The distribution of myeloma proteins did not differ from that reported in MM.

Furthermore, there was complete concordance between immunoglobulin class of paraprotein and intracytoplasmatic Ig.
Acetylesterase in Lymphoblastic Leukaemia Associated with Thymic Enlargement
Authors: Barr Ronald D. , Koekebakker Marijke , Cameron Fiona , Rand Carol A. , Honig George R.
Published: August 2010

Focal cytoplasmic acetylesterase activity was sought in the malignant cells of 91 consecutive children with acute lymphoblastic leukaemia, of whom 10 had an anterior mediatstinal mass at diagnosis. This subgroup with thymic disease (TD) was characterized by hyperleucocytosis, the total leucocyte count being greater than 200 times 109/1 in 6 patients. Furthermore, there was a significant association (P < 0.025) between TD and the presence of leukaemic blast cells expressing a thymic phenotype, in the form of rosette formation with sheep erythrocytes. Focal cytoplasmic acetylesterase activity identified TD with a sensitivity of 20%, a specificity of 91 %, a positive predictive value of 25 %, a negative predictive value of 88 % and a diagnostic accuracy of 81%. The demonstration of this feature by a simple cytochemical technique can be a useful component of the profile of investigations which are employed in the classification of acute lymphoblastic leukaemia.
Influence of the Pure Synthetic PAF (Platelet Aggrregating Factor) on Clot Retraction and Platelet Aggregation
Authors: Bottecchia Domenico , Fantin Giampaolo , Doni Maria Gabriella
Published: August 2010

Pure synthetic platelet aggregating factor (PAF) (1‐O‐Hexadecyl‐2‐acetyl‐sn‐glycero‐3‐phosphorylcholine) induces a dose‐dependent platelet aggregation in platelet‐rich plasma (PRP) and in gel‐filtered platelets. Irreversible platelet aggregation was observed at final concentrations of PAF higher than 2 times 10‐7 mol/l, while reversible or two‐wave aggregation was obtained with lower final concentrations. The second wave was inhibited by acetylsalicylic acid, indomethacin, dipyridamole, EDTA, EGTA, theophylline, caffeine, PGE1 and verapamil. PAF does not induce reptilase clot retraction (RCR); however, it does not inhibit RCR induced by ADP or thrombin. Since all substances known to activate platelets also induce RCR, the lack of this activity by PAF would support the existence of a third pathway in platelets.
Iron overload in patients with haemoglobin H disease
Authors: Tso S. C. , Loh T. T. , Todd D.
Published: August 2010

Serum ferritin was measured in 46 Chinese patients with Hb H disease (HbHD) and compared with 84 controls according to age group. Ferritin levels were elevated in 14 of 20 males and 20 of 26 females and the extent of the abnormality increased with age. Splenectomy did not appear to be associated with particularly high levels of serum ferritin in this disease.
Chemotherapy resolves symptoms and reverses marrow fibrosis in myelofibrosis
Authors: Manoharan A. , Pitney W. R.
Published: August 2010

12 patients with symptomatic chronic myelofibrosis were treated with either busul‐phan or 6‐thioguanine. Therapy was without significant side effects and resulted in a reduction in the size of liver and spleen and an improvement in well‐being in all cases. In 7 patients the Hb value rose and the extent of marrow fibrosis was reduced in the 5 patients in whom bone marrow examination was repeated after treatment. Chemotherapy is an effective and safer alternative to splenectomy in patients with myelofibrosis with symptomatic anaemia, symptomatic splenomegaly or constitutional symptoms such as fever, weight loss and night sweats.
Reduced lung function in leukaemia patients undergoing bone marrow transplantation
Authors: SøRENSEN P. G. , ERNST P. , PANDURO J. , MøLLER J.
Published: August 2010

20 patients with leukaemia in remission or early relapse received an allogeneic bone marrow graft. Patients were conditioned according to Seattle protocol with high dose cyclophosphamide and total body irradiation to a total dose of 8 Gray to the lungs delivered by a 6 MV linear accelerator at a dose rate of approximately 0.06 Gray/min. As prophylaxis against the graft versus host reaction, methotrexate and/or cyclosporin A were given.

Lung function was studied prior to treatment and every 3 months thereafter. Before treatment a marked decrease was seen in the CO diffusion capacity when compared to the predicted value, while the flow volume relationships were within normal limits. The cause of this is unknown, but may be due to previous infections and the cytostatic treatment given. After bone marrow transplantation, a further irreversible decrease was seen in the CO diffusion capacity and vital capacity indicating an additive effect of the lung irradiation.
Blood coagulation in patients with benign and malignant tumours before and after surgery Special reference to thromboplastin generation in monocytes
Authors: ØSTERUD B. , Jr. J. DUE
Published: August 2010

In this study we have looked for differences in coagulation parameters before and after surgical removal of benign or malignant tumours. A striking increase in thromboplastin activity of the blood monocytes was seen 1 d after surgery. This paralleled a fall in factor VII activity. At the same time, the sensitivity of the blood monocytes to stimulation by endotoxin increased significantly. We propose from this study that monocyte thromboplastin may be a postoperative thrombogenic factor. Increased levels of factor VIII and fibrinogen 2–3 d postoperatively were found, probably caused by inflammation reactions induced by the surgery. No difference in coagulation parameters could be demonstrated between patients with benign, noninvasive lesions and patients with invasive, carcinomatous lesions.
Role of sialyltransferase in hypercupraemia of non‐Hodgkin's lymphoma
Authors: SHAH ILA , CHOU Ta‐HSU , TAPAZOGLOU EFSTATHIOS , KESSEL DAVID
Published: August 2010

Copper, ceruloplasmin and sialyltransferase activity were measured in serum of 25 patients with lymphoreticular malignancies, in an attempt to study the sialyltransferase activity and correlation if any with the activity of the disease and ceruloplasmin. All 3 parameters were elevated in active disease but no definite correlation between sialyltransferase activity and copper or ceruloplasmin could be found. We conclude that plasma sialyltransferase activity is increased in lymphomas.
Red‐Cell Sensitization in Myelofibrosis
Authors: Hasselbalch Hans , Berild Dag , Hansen Ole Paaske
Published: August 2010

Using an enzyme‐linked immunosorbent assay (ELISA), elevated RBC‐Ig of the IgG and IgM class were found in 8 of 14 patients with idiopathic myelofibrosis. In 2 patients with high levels of RBC‐Ig the direct Coombs' test was positive. It is supposed that immune haemolysis may contribute to the anaemia in some patients with idiopathic myelofibrosis.
Impaired monocyte differentiation in children with acute lymphoblastic leukaemia: its evaluation by peroxidase activity and ultrastructure
Authors: YODA SATORU , TSUKADA MASASHIGE , HARA YOJI , KOMIYAMA ATSUSHI , AKABANE TARO
Published: August 2010

The ability of monocyte differentiation in childhood acute lymphoblastic leukaemia (ALL) was evaluated on the basis of the ultrastructure and peroxidase (PO) activity which could show the differentiation of cultured monocytes. In the control, PO activity limited to the granules decreased time‐dependently during culture for 4 d, and was closely associated with the morphological development to macrophages. In childhood ALL, monocytes showed poor changes in both PO activity and morphological features during culture for 4 d compared to the control. Therefore, we conclude that monocyte to macrophage differentiation is impaired in childhood ALL.
Increased ferritin synthesis and iron uptake in inflammatory mouse macrophages
Authors: Birgegård Gunnar , Caro Jaime
Published: August 2010

Iron metabolism during inflammation was studied in normal and stimulated peritoneal mouse macrophages. A model was developed for detection of ferritin synthesis in these cells, and inflammatory stimulation was produced by i.p. injection of thioglycollate broth or i.m. injection of turpentine. The cells were adhered to culture discs and incubated at 37°C with59Fe‐transferrin and3H‐leucine, and after washing the cell lysate was chromatographed. In the lysate from stimulated macrophages iron and tritium activity was found in a joint peak, and both were precipitated by a specific anti‐mouse ferritin antibody. No significant peaks of radioactivity were found in lysates from normal cells. This showed that inflammatory RES cells have an increased ferritin synthesis. The uptake of59Fe was investigated in a separate study and the stimulated macrophages were found to have a much higher iron uptake than normal macrophages.
A family with sickle cell trait and hereditary spherocytosis
Authors: Babiker Malik Ahmed , Seed Fateh Al Rahman A. El
Published: August 2010

The rare combination of sickle cell trait with hereditary spherocytosis in a Sudanese family is reported. The splenic hypofunction and fibrosis as a result of sickling has ameliorated the clinical course of the 35 year old father. The symptoms of a six years old son seem to be getting milder with age too. The family is managed conservatively and splenectomy was not required.
Defective intrinsic fibrinolytic activity in a patient with severe factor XII‐deficiency and myocardial infarction
Authors: Lodi Sergio , Isa Luciano , Pollini Ettore , Bravo Alberto Ferrari , Scalvini Augusto
Published: August 2010

The paper reports the occurrence of myocardial infarctions in a patient with severe deficiency of blood coagulation factor XII (Hageman factor). Factor XII plays a central role in the intrinsic activation of fibrinolysis and consequently the defective intrinsic fibrinolytic activity detected in the present case casts some doubt on its role in the increased vulnerability to thrombotic accident.
Immunochemical characterization of platelet‐specific alloantigens
Authors: Mulder Arend , van Leeuwen Eleonora F. , Veenboer Geertruida J. M. , Tetteroo Pedro A. T. , von dem Borne Albert E. G. Kr.
Published: August 2010

Immunoprecipitation was performed with platelet‐specific alloantisera (anti‐Zwa, ‐Zwb, ‐Baka and antiserum Luc) and 125I‐labelled platelets of a panel of donors typed for these platelet‐specific alloantigens. This was done by sensitization of intact, radiolabelled platelets with the antisera, solubilization of the sensitized platelets with Nonidet P‐40 and recovery of the immune complexes from the lysate with heat‐killed, formalin‐fixed Staphylococcus aureus, strain Cowan I. In the case of platelet antibodies of the IgM class, bacteria also preincubated with rabbit‐IgG anti‐human IgM before treatment of the lysate were applied. Radiolabelled antigens were then eluted from the bacteria by boiling in an SDS‐mercaptoethanol‐containing buffer. Subsequently, the eluted antigens were analyzed by SDS‐polyacrylamide gel electrophoresis. It revealed that both the Zwa and the Baka antigens are located on the glycoprotein‐IIb/IIIa complex. The location of the Zwb antigen could not be established in this way.

From the intensity of the precipitated glycoprotein bands, it appeared that Zwa is probably a marker of glycoprotein IIIa, Baka or glycoprotein IIb. However, immuno‐precipitates of anti‐Zwa and anti‐Baka sera both carried, to some extent, complexes of glycoproteins IIb and IIIa. Iodinated platelets of a Glanzmann thrombasthenia patient failed to show any material precipitated by these antisera or the antiserum Luc, known to contain antibodies against both glycoproteins.
IgG2 deficiency in sickle cell anaemia
Authors: Natta Clayton L. , Outschoorn Ingrid M.
Published: August 2010

8 patients with known sickle cell anaemia were studied immunologically. The concentrations of the main immunoglobulin classes, IgG and IgA, were significantly higher than the levels in 11 normal age‐ and sex‐matched black subjects (P < 0.01). IgM levels were not significantly different in the two groups. There was a heterogeneity in the interaction of the IgG subclasses with Protein A, with low levels of IgG2. The IgG2:IgG1 ratios varied from 1:3.8 to 1:6 (normals 1:3). In 4 patients the absolute levels of IgG2 as measured by radial immunodiffusion were lower than normal, thus confirming the chromatographic ratios. Since specific antibody is often restricted to a single subclass, the levels of IgG subclasses may be related to recurrent bacterial infections in these patients.
Hemophilia and the Family: Life‐Long Challenges and Adaptation
Authors: Mattsson Å.
Published: August 2010

To live with hemophilia presents many long‐term psycho‐social stresses, in addition to the painful and often immobilizing physical symptoms. Among the psychological stress factors are the impact on the family of raising a hemophilic boy, the patient's coping with frequent hospitalizations often involving infusions and orthopedic care, patient and his family learning the aspects of home care, and the common uncertainties relating to the hemophiliac's social adjustment and educational and professional future. These aspects of the life of hemophiliacs will be presented by the use of an open systems model which allows for delineation of the many interrelationships of the hemophiliac which have to be considered by the comprehensive care team. The maturation of the mind of a young hemophiliac, that is his cognitive functions, and the existence of stable family functioning and open communication within the family and with the health care team are essential allies in promoting a healthy psychosocial development of the hemophiliac.
The Use of Desmopressin (DDAVP) in the Preparation of Improved Factor VIII Concentrate
Authors: Mikaelsson M , Nilsson I M , Cedergren B , Jonsson S , Rydberg L , Wiechel B
Published: August 2010

Blood was drawn after the intranasal administration of 325 μg DDAVP from altogether 420 blood donors at 5 blood banks in Sweden. No significant side‐effects were observed. The DDAVP plasma was pooled in two separate batches. Matched pools of control plasma from the same donors were also prepared. From each pool a separate batch of high purity factor VIII concentrate (Octonativ) was produced.

The yield of VIII:c in the DDAVP batches was 2.6 and 1.5 times higher than in the corresponding control batches. The specific activity was 2.8 for the two DDAVP batches and 2.0 IU/mg protein for the control batches. The in vivo recovery was about 100 per cent for all the batches when examined in 5 patients with severe haemophilia a. The individual half‐lives (late phase 5–48 hours) varied between 7 and 17 hours. No significant differences between the batches derived from the DDAVP and the control plasma could be detected.

Thus, intranasal DDAVP seems to be a safe and practicable means of improving the production of factor vIII concentrates.
North American Study of Factor VIII Concentrate Potency
Authors: Lusher J M , Ofosu F A , Edson J R , Joist J H , Chavin S I , Weiss A E , Hillman C R L
Published: August 2010

In view of reports of less than labelled F VIII:C content in some lots of commercially available f VIII concentrates, a multi‐center prospective study of f VIII concentrate potency was organized in collaboration with the United States Bureau of Biologics (BoB). Phase one of the study was aimed at evaluating the reproducibility of F VIII:C assays (one stage) in the participating laboratories, using: 1) A uniform assay method, and 2) Each lab's in‐house method. Reproducibility was better with the latter. Phase two consisted of: 1),In vitroassays of currently available F VIII concentrates, and 2)In vivoF VIII:C recovery studies in two severe hemophilia A subjects. Three different lots of concentrate from each of eight different products were used for these studies. Lots were randomly selected from those available in spring‐summer 1982.

Each lab used its in‐house F VIII:C method, with lyophilized standards provided by BoB. All values were read against three standards: In‐house, BoB A (concentrate standard) and BoB s (plasma standard). Baseline, 15 and 45 minute samples from thein vivorecovery studies were snap‐frozen and stored at ‐70°C, then shipped in dry ice. All plasma samples were assayed as unknowns in each of nine participating labs (the authors‘, Hyland, Cutter and BoB). Statistical analysis of data for 24 lots of concentrate (three lots each from Cutter, Hyland, Alpha, Armour, N.Y. Blood Center, American Red Cross‐Cutter, American Red Cross‐Hyland, Michigan Department of Health) revealed the following: Inter‐lab values of in vitro assays of concentrate compared best when BoB A (concentrate standard) was used. Mean values corresponded to those on the manufacturers' labels, and in some instances were higher. In vivo studies revealed better than “expected” F VIII:C recovery with each product tested. In the in vivo studies inter‐lab values (for f VIII:C assays of the plasma samples) compared very well when BoB 5 (plasma standard) was used. In bothin vitroand in vivo studies there was much greater inter‐laboratory variation in results when in‐house standards were used.
Principles of in vivo Recovery and Survival Studies
Authors: Allain J‐P
Published: August 2010

Factor VIII preparations available to the clinician are numerous and vary greatly in their mode of preparation, potency, purity and potential side effects. In vivo behaviour of Factor VIII:C from each product should be studied systematically. Collection of useful and valid information on VIII:C recovery and half‐life requires the observance of rather strict rules.

Standards. The dose of infused VIII:C can be calculated either from the labeled value or from local measurement using as reference a concentrate calibrated against the WHO concentrate standard. VIII:C plasma levels are tested using a plasma reference calibrated against the WHO plasma standard.

Patients. Severe hemophilia A patients non bleeding or bleeding in small capacity joint and not treated for at least five days without inhibitor are selected.

Dose. At least 20 u/kg body weight of VIII:C are infused.

Sampling. Plasma samples collected before, 15, 30 and 60 minutes post‐infusion allow to identify the peak of VIII:C activity from which in vivo recovery is calculated. Samples collected 4,8–12,24 and 36–48 h post‐infusion allow to evaluate F VIII:C half‐life on the basis of VIII:C plasma levels measured in 4 of these samples.

Assays. VIII:C one or two‐stage assays are equally acceptable although only one‐stage assays detect activated VIII:C. Plasma samples from a patient are stored at ‐70°C and all tested in one session.

Calculations. In vivo recovery is estimated as percent of a theoretical value obtained either on the basis of 1 u/kg VIII:C provides 0.02 u VIII:C/ml plasma or of a calculated plasma volume. Various calculation programs seem suitable for evaluation of VIII:C half‐life.
Suppression of Secondary Antibody Response by Intravenous Immunoglobulin and Development of Tolerance in a Patient With Haemophilia B and Antibodies
Authors: Nilsson I. M. , Sundqvist S.‐B.
Published: August 2010

A patient with severe haemophilia B and high response antibodies was twice treated with extracorporeal adsorption of the antibodies to protein A. An interval of two years separated the two occasions, the same procedure ‐ substitution therapy and immunosuppression (cyclophosphamide) ‐ being followed on both, with the exception that intravenous immunoglobulin was included on the second occasion. Within a week after the first treatment his antibody titre had risen 15‐fold, while no secondary antibody response was noted following the second. Since then the patient has been treated a further 16 times ‐ without any secondary antibody response occurring; once with factor IX in combination with i.v. IgG and immunosuppression, twice with factor IX and i.v. IgG and 14 times with factor IX only.

It seems likely that antibody synthesis was suppressed by the i.v. IgG. No evidence has been found for such mechanisms such as nonspecific suppression or blocking effect of the IgG on factor IX antibodies. However, the possibilities of a combined effect of the adsorption technique, immunosuppression and i.v. IgG cannot yet be ruled out.
A Tissue Culture Model of Cartilage Breakdown In Haemophilic Arthropathy
Authors: Smith P.D. McLardy , Ashton I.K. , Duthie R.B.
Published: August 2010

Synovium in tissue culture has a degradative effect on cartilage which is partly chemically mediated. This effect has been shown to be more marked in the inflammatory arthropathies. The possibility of similar effects of haemophilic synovium were investigated.

Synovial tissue from patients with either chronic haemophilic arthropathy, rheumatoid arthritis or no inflammatory arthropathy was cultured. The prostaglandin production of the tissue in culture, and the effects of the haemophilic synovium conditioned medium (HCM) on human cartilage were compared.

Results show that haemophilic synovium produces prostaglandin E in culture, at markedly higher levels (upto 872 pg/mg synovium/hour n = 11) compared with normal (maximum 217 pg/mg/hour; n = 3). The HCM also stimulated glycosaminoglycans breakdown and decreased retention of newly synthesised chondroitin sulphate (CS) in cartilage cultured in it when compared to the normal conditioned medium (NCM). Expressed as a percentage of CS in the whole culture system after 14 days co‐culture, CS lost from the cartilage compared to controls was 11.7% (S.E. 3. 4, n = 6) for HCM and 1.8% (S.E. 0.6 n = 4) for NCM. In comparison in two rheumatoid conditioned media (RCM) the loss was 14.7% and 12.6%. a similar effect has been demonstrated for haemophilic synovium as has previously been reported for rheumatoid synovium.
Ultrasonic Measurements of Haematomata of Joints and Soft Tissues in the Haemophiliac
Authors: Kinnas P.A. , Woodham C.H. , MacLarnon J.C.
Published: August 2010

Both soft tissue haematomata and haemarthroses in haemophilic patients have been investigated by using ultrasonic techniques. Findings have been evaluated for their usefulness in diagnosis with particular reference to size, demarcation and the topographic situation of the haematoma. The volume of the blood collection was estimated from measurements made on the B‐scan, and serial scans were performed to estimate changes in volume during treatment.

This simple method, which is without risk to the patient, is a useful adjunct in the evaluation and follow‐up of haematomata of joints and soft tissues.
Arthroscopic Synovectomy of the Knee Joint with the Electric Resectoscope
Authors: Aritomi H
Published: August 2010

The design and function of electric resectoscope, consisting of arthroscopy with an electric surgical knife, is described in association with the technique of arthroscopic surgery in the knee joint of non‐hemophilic patients.

Arthroscopic surgery with the electric resectoscope can extend its indication to synovectomy and removal of loose bodies as well as cartilage shaving. Clinical follow‐up results suggested that this arthroscopic synovectomy demonstrated almost comparable results to those of conventional synovectomy.

The advantages of arthroscopic surgery with the electric resectoscope are the following: It can perform arthroscopic surgery as well as synovectomy with resectoscope through small skin incision. It can effect intraarticular hemostasis by electrocoagulation with resectoscope. Postoperative pain is far less than the conventional synovectomy. It offers much more rapid recovery of range of motion of the joint without any manipulation post‐operatively. Consequently, it shortens the period of hospitalization.

None of the complications were serious except for two episodes of infection with Pseudomonas during the early practice of this technique.
A Proposed System of Classification of Hemophilia Centers for the World Federation of Hemophilia (W.F.H.)
Authors: Levine P H , Brackmann H H , Seligsohn U
Published: August 2010

At the request of the executive of the World Federation of Hemophilia, a uniform system for the classification of hemophilia centers has been devised. Three levels of centers are described: the hemophilia treatment unit, the comprehensive hemophilia center, and the comprehensive hemophilia reference center. It is hoped that adoption of this system will assist hemophilia treaters in being able to develop more complete and comprehensive services, with the recognition and support of local and national governments and health agencies.
Fractionation of Factor VIII and IX ‐ An Overview
Authors: Johnson A.J. , Mathews R.W. , Fulton A.J.
Published: August 2010

The recent development of concentrated plasma fractions for the treatment of Hemophilia A (factor VIII:C) and Hemophilia B (factor IX) has greatly facilitated replacement therapy in patients with congenital deficiencies of these components and has proven essential for home therapy with normalization of the patients' life style.

Preparation of the concentrates requires adequate amounts of high quality plasma frozen promptly to preserve the activity of the coagulation factors. In a large, regional blood center in the U.S. the average potency of the fresh‐frozen, single‐donor plasma averaged about 1.0 U/ml over a period of four years. The effectiveness, cost, incidence of reactions and potential for transmission of hepatitis vary with the purity and yield of the concentrates, and possibly the size of the initial plasma pool from which the concentrate is derived. The higher the purity, the greater the solubility, concentration and convenience, and the lower the potential toxic effects, including possible contaminating viruses. The higher the yield, the lower the cost to the producer and consumer. The larger the starting pool of plasma, the greater the likelihood of contamination with hepatitis virus or (possibly) acquired immune deficiency syndrome (AIDS).

The comparative advantages and disadvantages of the various fractionation methods are explored together with the areas of optimal usefulness, including hemophilia A and hemophilia B with and without endogenous inhibitors. Some attention is also given to the comparative freedom of most concentrates from contamination by hepatitis B, non‐A, non‐B, and possibly AIDS.
METHODOLOGY OF THE ONE‐STAGE ASSAY OF FACTOR VIII(VIII:C)
Authors: Over Jan
Published: August 2010

ABSTRACT:  In this chapter several aspects of the one‐stage assay for Factor VIII coagulant activity (VIII:C) are discussed, based both on a survey of the literature and on experimental data. Special attention is paid to the variables present in the assay system and their influence on coagulation times and Factor VIII estimates. Recommendations are given on how to carry out the assay properly and finally two examples of an assay system are presented.
NON FACTOR VIII RELATED CONSTITUENTS IN CONCENTRATES
Authors: Allain Jean‐Pierre
Published: August 2010

ABSTRACT:  Factor VIII preparations contain a variety of components unrelated to the Factor VIII complex which represents only a trace protein. Some of these “contaminants” are plasma proteins, mainly fibrinogen, fibronectin, IgG, IgM and albumin accounting for over 70 per cent of the total protein content. Biologically active proteins such as AT III, Factor XIII, proteolytic enzymes and prekallikrein activator are also present and may interfere with clinical tolerance of Factor VIII activity. However, immunoglobulins are the major source of side effects related to both the structure and the specificities of these molecules. Hemolysis caused by anti‐A or anti‐B allo‐agglutinins is a well characterized side effet. Various chemicals added during the purification process of the final product are found in the therapeutic concentrates. Viral infective agents originating from unscreened donors contaminate large plasma pools and concentrates. Viruses related to hepatitis (B hepatitis, non‐A, non‐B hepatitis, CMV, EBV) or not formally pathogenic (HTLV, LAV, Parvovirus) are transmitted by Factor VIII infusion and a high incidence of specific viral markers are found in hemophilia A patients. The iatrogenic role of these constituents in the short or long term should be thoroughly evaluated.

Factor VIII related proteins are only a very small fraction among the numerous components present in the so called “Factor VIII concentrates”. Recipients are therefore submitted to various hazards related to: other human proteins which copurified with Factor VIII; infective agents, primarily viruses, whose large molecular weights tend to follow large molecular weight proteins like the Factor VIII complex; trace amounts of various chemicals used during the purification process. Since most hemophilia A patients are repeatedly treated with these complex mixtures, it is of primary importance to identify these components termed “contaminants” and to evaluate their potential side effects in immediate, short and long terms. This chapter will list these contaminants irrespective of their potential iatrogenic value and indicate briefly some of their harmful consequences.
Functional and multimarker analysis of T‐cell chronic lymphocytic leukaemia
Authors: Baldini L. , Di Padova F. , Cortelezzi A. , Neri A. , Nobili L. , Lavezzi A. M. , Maiolo A. T. , Polli E. E.
Published: August 2010

The morphology, immunophenotype, cytoenzymatic and functional activities of T lymphocytes from 4 patients with chronic lymphoproliferative disease of T‐cell origin were studied. Clonal proliferation was demonstrated by distinctive chromosomal abnormalities involving chromosomes 2 and 14. Patients 1 and 2 were classifiable as OKT4+ T‐cell chronic lymphocytic leukaemia (T‐CLL) and patient 3 as OKT4+/OKT8+ T‐CLL, with helper function in vitro only in patient 1. Patient 4 has low‐grade lymphocytosis with benign clinical course, with cells showing morphology of large granular lymphocytes (LGL), and immunophenotype HNK‐1+, ER+, Fcy receptor+, OKT3+, OKT11+ and OKT8+, as well as natural killer activity, radiosensitive suppressor activity on Ig secretion and responsiveness to PHA; this case was interpreted as LGL leukaemia. This study indicates that a large proportion of cases of true T‐CLL may belong to the OKT4 subset, and that extensive investigations should be made of the lymphocytic OKT8+/Tγ forms to characterize them precisely.
Deficiency of fibrinogen and factor VII following treatment of severe aplastic anaemia with anti‐thymocyte globulin and high‐dose methylprednisolone
Authors: Fischer Margareta , Lechner Klaus , Hinterberger Wolfgang , Niessner Herwig , Pabinger Ingrid , Dudczak Robert , Neumann Erich , Korninger Christian , Deutsch Erwin
Published: August 2010

In 4 patients with SAA treated with ATG and high‐dose MP, an as yet unrecognized acquired deficiency of fibrinogen and factor VII was observed. The plasma level of fibrinogen fell to 39% (34–51%) and of factor VII:C to 50% (31–55%) of the pretreatment value. The nadirs were between days 10 and 35 (fibrinogen) and d 3 and 11 (factor VII) after the 1st dose of ATG/MP. From additional clotting studies it is concluded that disseminated intravascular coagulation, fibrinolysis, liver cell damage and synthesis of abnormal clotting factors are unlikely causes of these clotting abnormalities. The most probable explanation seems to be a selective inhibition of the synthesis of fibrinogen and factor VII by an as yet unknown mechanism. These clotting abnormalities might, to some extent, increase the bleeding tendency in these patients, which up to now had been solely attributed to thrombocytopenia.
Factors and inhibitors of blood coagulation and fibrinolysis in acute nonlymphoblastic leukaemia
Authors: Bratt G. , Blombäck M. , Paul C. , Schulman S. , Törnebohm E. , Lockner D.
Published: August 2010

Factors of coagulation and fibrinolysis have been evaluated in 15 patients with untreated acute nonlymphoblastic leukaemia (ANLL). 10 patients had major bleeding (MB) and 6 had laboratory signs of DIC. 5 patients went into complete remission (CR). Antithrombin III (AT III) was decreased in 7 patients, antiplasmin (AP) in 9, fibronectin (FN) in 6 and factor XIII in 4/12. The ratio between factor VIIIR:Ag and factor VIII:C was over 2.0 in 11 patients, and high values were especially seen in patients with MB and patients with DIC. Spontaneous proteolytic activity, measured with S‐2288 was increased in 3 patients who all had MB, and none of whom achieved CR. 2 patients with promyelocytic leukaemia (M3) had low fibrinogen and AP, high FDP and normal AT III, speaking for primary fibrinolysis, which in addition to proteolytic enzymes in the blast cells are important contributing factors regarding MB in ANLL.
Serum immunosuppressive acidic protein in adult T‐cell leukaemia (ATL)
Authors: Tagawa Shinichi , Sawada Masumi , Tokumine Yukihiro , Ueda Etsuko , Machii Takashi , Hayashi Satoru , Kurata Yoshiyuki , Kitani Teruo
Published: August 2010

The availability of serum immunosuppressive acidic protein (IAP) as a marker of subtypes of adult T‐cell leukaemia (ATL) was examined. Serum IAP levels were measured in 34 patients with ATL (18 typical, 9 atypical and 7 smoldering), 7 healthy carriers of ATLA antibody and 53 healthy controls. The mean value of serum IAP was significantly higher in patients with typical ATL (897.8 + 502.4 μg/ml) than in those with atypical ATL (426.7 + 106.6 μg/l), smoldering ATL (310.0 + 51.3 μg/ml), healthy carriers of ATLA antibody (302.9 + 39.5 μg/ml) and normal controls (350.5 + 73.2 μg/ml). Serial determinations of IAP revealed that the level was correlated with the clinical course in patients with ATL; there was a difference in the prognosis of patients with high and normal levels of IAP (P < 0.05). Thus, routine measurement of serum IAP seems useful in differentiating typical, atypical and smoldering ATL and also in evaluating the prognosis of patients.
Influence of splenectomy and the functional hyposplenism of coeliac disease on platelet count and volume
Authors: O'Grady J. G. , Harding B. , Stevens F. M. , Egan E. L. , McCarthy C. F.
Published: August 2010

Platelet count and volume were measured in 84 splenectomised subjects, 142 patients with coeliac disease and 77 healthy subjects. An inverse, non‐linear correlation between platelet count and volume was found in healthy subjects and coeliac patients, but was not present in splenectomised subjects who had higher platelet counts (P = 0.0001) and mean platelet volumes (P = 0.0001) than healthy subjects. Platelet counts correlated with splenic function in patients with coeliac disease and were higher in patients with severe hyposplenism than in normosplenic coeliacs (P = 0.0001). Splenic function did not influence the mean platelet volume (MPV) in coeliac disease but normosplenic coeliacs had higher MPV than normal subjects (P = 0.05). Serum iron and red cell folate were not correlated to MPV in coeliac disease. We conclude that splenic function effects platelet count and volume in non‐coeliac subjects and platelet count in coeliac disease. However, other unidentified factor(s) influence the MPV in coeliac disease.
Chylomicronaemia in multiple myeloma
Authors: Aviram Michael , Carter Anna , Brook J. Gerald , Tatarsky Ilana
Published: August 2010

A patient with multiple myeloma presented with an accumulation of chylomicron‐like particles. This rare finding resembled that of the type V hyperlipoproteinaemia phenotype. The lipid and lipoprotein concentration and composition were compared with values obtained from other patients with multiple myeloma, patients with the type V hyperlipoproteinaemia phenotype (accumulation of chylomicrons and very low density lipoproteins), and normal subjects. An immunoglobulin‐lipid complex was demonstrated in our patient. This complex was found not to be associtated with the chylomicrons and was detected only in the lipoprotein‐dificient plasma. Lipid and lipoprotein concentration and composition differed from the other groups. Very low density lipoprotein concentration was reduced, and there was thus a marked difference from the type V phenotype. The chylomicrons derived from this patient were also richer in apolipoprotein C compared to chylomicrons derived from the patients with type V hypolipoproteinaemia. It appears that the abnormal composition of the triglyceride‐rich lipoproteins observed in this patient renders her refractory to the normal pathways of metabolism.
SIDEROBLAST COUNT AND EXAMINATION OF BONE MARROW RETICULOENDOTHELIAL IRON IN THE DIAGNOSIS OF IRON DEFICIENCY
Authors: Rybo Elisabeth , Bengtsson Calle
Published: August 2010

Bone marrow smears from 38‐year‐old women participating in a population study were examined with respect to stainable iron in reticuloendothelial cells and in erythroblasts called sideroblasts. Blood haemoglobin concentration, erythrocyte mean corpuscular haemoglobin and transferrin saturation in serum were lower in women with no stainable iron in the reticuloendothelial cells and sideroblast counts below 16 % than in women with stainable iron clearly visible and sideroblast counts equal to or above 16 %. Iron absorption was higher and menstrual blood loss heavier in women with no iron than in women with stainable iron, irrespective of the number of sideroblasts. Examination of reticuloendothelial iron was a more effective method for defining iron deficient subjects than was the counting of sideroblasts.
SERUM FERRITIN CONCENTRATION COMPARED TO OTHER IRON‐STORE VARIABLES IN THE DIAGNOSIS OF IRON DEFICIENCY
Authors: Rybo Elisabeth , Bengtsson Calle , Hallberg Leif , Lindstedt Göran , Lundberg Per‐Arne
Published: August 2010

Serum ferritin concentration was determined in 38‐year‐old women representative of the general female population of the same age resident in Gothenburg, Sweden. The assays were carried out on serum samples which had been frozen (‐22° C to ‐28° C) for ten years. The values were related to haematological variables which had been examined at the time of the initial study. The distribution of serum ferritin values was markedly positively skewed. Woman with a serum ferritin concentration within the lowest three decentiles had the heaviest menstrual blood loss, no or only traces of reticuloendothelial iron in sternal bone marrow and high iron absorption of a tracer dose of labelled iron. High correlation coefficients were obtained when correlations were calculated between serum ferritin and transferrin saturation, sideroblast count in bone marrow and iron absorption. The correlation coefficients were usually higher between serum ferritin concentration and the other haematological variables than the correlations between the individual haematological variables. There was good agreement between the prevalence of reticuloendothelial iron in bone marrow and serum ferritin concentration. We conclude that bone marrow examination may be replaced by determination of serum ferritin concentration when screening for iron deficiency in otherwise healthy subjects. This seems to be relevant also in subjects with a history of recent mild infection or current use of oral contraceptives.