bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Clefts in Chronic Lymphocytic Leukaemia A Light Microscopic and Ultrastructural Study of a New Prognostic Parameter
Authors: Ralfkiær Elisabeth , Geisler Christian , Hansen Mogens Mørk , Hou‐Jensen Klaus 
Published: August 2010

Peripheral blood lymphocytes from 48 consecutive, newly diagnosed CLL patients were examined by light‐ and electron‐microscopy for the presence of nuclear cleaving or folding. On this basis, the patients could be subdivided into 2 easily separable morphological groups. In 42 patients the lymphocytes had regular round nuclei. In 6 patients (13 %) the lymphocytes of peripheral blood had a highly irregular nuclear outline characterized by pronounced cleaving or folding of the nuclear membrane. In 4 of these 6 patients immunological investigations demonstrated membrane markers consistent with B‐cell monoclonality. Age, sex, distribution between stages as well as mode of clinical presentation were all alike in the 2 groups of patients. In spite of this a statistically significant, highly increased mortality was observed in patients with lymphocyte nuclear irregularities. Thus, 50% of all deaths occurred in this small group of patients.These findings indicate that lymphocyte nuclear cleaving or folding represents a stage‐independent prognostic parameter, which permits selection of a small but easily identified high‐risk group of patients.
Antibody Response to Pneumococcal Vaccination in Patients with Myelomatosis
Authors: Birgens Henrik S. , Espersen Frank , Hertz Jesper B. , Pedersen Freddy Karup , Drivsholm Aage 
Published: August 2010

17 patients with myelomatosis were vaccinated with a 14‐valent pneumococcal capsular polysaccharide vaccine. In comparison to 12 healthy controls, they had statistically significant lower combined geometric mean antibody concentrations (the geometric means of all 14 antigens), both before and 4 weeks after the immunization. Mean antibody increases, however, were remarkably similar in the 2 groups. After 18 months the geometric mean antibody concentrations of the patient group had returned to preimmunization levels or lower for 7 out of 14 antigens. 1 case of pneumococcal bacteraemia occurred in the patient group 8 1/2 months after vaccination in spite of a significant initial antibody response against the infecting serotype 23 F.Pneumococcal vaccination in patients with myelomatosis appears to yield subnormal antibody responses and therefore probably insufficient protection against pneumococcal infection.
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.
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.
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.
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.
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.
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.
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.
SIDEROBLAST COUNT AND EXAMINATION OF BONE MARROW RETICULOENDOTHELIAL IRON IN THE DIAGNOSIS OF IRON DEFICIENCY
Authors: Rybo Elisabeth , Bengtsson Calle 
Published: August 2010

ABSTRACTBone 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.