bluuebunny/crossref_metadata_2025 huggingface dataset:
Low antithrombin in severe disease: Consumption or decreased synthesis?
Authors: ANKER ERIK , ABILDGAARD ULRICH , ANDERSEN RAGNAR , FAGERHOL MAGNE , BJUNE GUNNAR
Published: August 2010

Haemostasis parameters alone are often insufficient in distinguishing between disseminated intravascular coagulation (DIC) and liver disease. We have determined the concentration of five additional plasma proteins in 6 patients with DIC and 10 patients with liver disease. All patients had antithrombin III (AT) and normotest (NT) levels at 60 per cent or lower. Prealbumin and albumin were clearly subnormal in all patients with similar mean values in both two groups. It is suggested that this might reflect insufficient protein synthesis even in the patients with DIC. The mean fibronectin concentration was somewhat lower in DIC than in the group with liver disease. C reactive protein (CRP) and the leucocyte derived protein LI were much higher in the DIC patients, probably reflecting the underlying infection.
K‐Cell Activity in Aplastic Anaemia
Authors: Voltarelli J. C. , Falcão R. P. , Carvalho I. F. , Bottura C.
Published: August 2010

K‐cell activity was measured by specific cytotoxicity and cytotoxic capacity in 29 patients with aplastic anaemia. 9 patients had a reduction of the specific cytotoxicity and 12 had a decreased cytotoxic capacity. The decreased cytotoxic capacity correlates with the severity of aplastic anaemia. Some of the possible causes of the reduction of this activity were investigated.
Suppression of Secondary Antibody Response by Intravenous Immunoglobulin in a Patient with Haemophilia B and Antibodies
Authors: Nilsson I. M. , Sundqvist S.‐B. , Ljung R. , Holmberg L. , Freiburghaus C. , Björlin G.
Published: August 2010

A 39‐year‐old patient, suffering from severe haemophilia B and antibodies against factor IX, has twice been treated with extracorporeal protein A‐Sepharose adsorption followed by conventional substitution therapy in combination with immunosuppression (cyclophos‐phamide). On both occasions, separated by a 2‐year interval, the same procedure was followed except that, on the second, administration of i.v. immunoglobulin (Gammonativ, KabiVitrum) was added. Within a week of the first treatment the patient developed a 15‐fold increase in the antibody titre. Following the second treatment described here, no secondary antibody response could be detected, and after a further 12 weeks only traces of antibodies are demonstrable. It seems that antibody synthesis was suppressed by the i.v. immunoglobulin. No evidence was found to demonstrate that the effect was due either to a non‐specific suppression of the immune and reticuloendothelial systems or to the action of interfering antibodies. It has not yet been established whether or not the protein A‐Sepharose adsorption technique, or the immunosuppressive treatment, contributed in any way to the result. The observations suggest a new approach to the treatment of haemophiliacs with antibodies of the high‐responding type.
Interferon‐α Treatment of a Patient with Acute Lymphoblastic Leukaemia and Down's Syndrome. Effects on Natural Killer Cell Activity and Mitogen Responsiveness
Authors: Bratt Göran , Einhorn Stefan , Blomgren Henric , Gahrton Gösta , Paul Christer , Strander Hans
Published: August 2010

A 32‐year‐old female with Down's syndrome and common ALL was treated with human leucocyte interferon‐α (IFN‐α) at a dose of 3 times 106 units i.m. daily. Side‐effects consisted of slight tenderness and localized haematomas at the sites of injection. During treatment the number of leukaemic cells decreased in the peripheral blood. The proportion of blast cells in the bone marrow decreased only slightly, but a large fraction of them became vacuolized. After the initial response the disease progressed and IFN was withdrawn after treatment for 67 d. Prior to initiation of IFN treatment the natural killer activity of the patient's lymphocytes, as well as the response of these cells to mitogenic stimuli, was low. During IFN therapy these functions increased. Following the withdrawal of IFN therapy the patient received vincristine/prednisone treatment and a complete remission was achieved after 5 weeks. She is still in remission and on maintenance therapy 24 months after initiation of treatment.
Combined Granulocyte and Platelet Transfusions: Inter‐Relationship between Granulocyte and Platelet Recoveries in the Presence and Absence of Complicating Factors
Authors: Ford John M. , Cullen Michael H. , Brown Linda M. , Roberts Marion M. , Fulford Anthony J. C. , Lister T. Andrew
Published: August 2010

191 combined collections of granulocytes (PMN) and platelets (PLT) obtained by discontinuous cytapheresis were given to 23 patients with acute myeloid leukaemia (AML). The circulation in recipients of the concomitantly transfused cells was compared by measuring the % recovery of PMN at 1 h, and of PLT at 1 and 20 h. The recovery of both cells was greatly reduced in transfusions accompanied by a transfusion reaction. Fever in recipients had no effect on the recovery of either cell, but PMN recovery was significantly higher in patients receiving oral prednisolone. Alloimmunization to PLT, defined as recovery levels less than 15% at 1 h and/or less than 10% at 20 h, was recorded in 42 transfusions, and PMN recovery was significantly reduced in this group. In transfusions where PMN recovery was ‘low’ (less than 5%); the recovery of the coincidentally transfused PLT was significantly reduced only in transfusions accompanied by a reaction. These results emphasize the deleterious effects of transfusion reactions and suggest that donor PMN frequently circulate less well in recipients alloimmunized to PLT from the same donor.
Reactivity of the monoclonal antibody RFB1 in chronic B‐cell leukaemias
Authors: Melo J. V. , Catovsky D. , Bodger M.
Published: August 2010

The monoclonal antibody RFB1, which reacts with early haemopoietic precursors in human bone marrow and peripheral T‐lymphocytes, but not with pre‐B cells and mature peripheral blood and marrow B lymphocytes, was tested in blood from 60 patients with chronic B cell leukaemias. All 37 cases of B chronic lymphocytic leukaemia (B‐CLL) and 9 of hairy cell leukaemia (HCL) were positive. The antibody showed particularly strong reaction in HCL. On the other hand, RFB1 did not react with peripheral blood and B lymphocytes from 9 patients with non‐Hodgkin lymphoma (NHL) in leukaemic phase and was negative or weakly expressed in 5 with prolymphocytic leukaemia (B‐PLL). These findings may be significant for investigations on the cell origin of B‐CLL and HCL. The reactivity of RFB1 was different from that of two anti‐T1 monoclonal antibodies. The combined use of these reagents gave distinct patterns in B‐CLL (RFB1+, T1+), HCL (RFB1++, T1‐) and NHL and B‐PLL (RFB1‐/±, T1‐/+), suggesting they may be of value in the differential diagnosis of these B‐lymphoproliferative disorders.
Unusual T cell proliferations and neutropenia in rheumatoid arthritis: comparison with classical Felty's syndrome
Authors: Linch David C. , Newland Adrian C. , Tumbull Alan L. , Knott Lesley J. , MacWhannel Alan , Beverley Peter
Published: August 2010

4 patients are described with rheumatoid arthritis, splenomegaly, neutropenia and an unusual proliferation of T cells in the blood and marrow. These patients are clinically similar to patients with classical Felty's syndrome but can be distinguished from them by staining blood and marrow mononuclear cells with a panel of monclonal anti‐T cell antibodies. The T cells from patients with T cell proliferations stain with UCHT1 (OKT3 equivalent) and UCHT4 (OKT8 equivalent but do not stain with a panel of OKTl‐like antibodies. In 7 patients with classical Felty's syndrome there was no increase of UCHT4 cells in the blood and the large majority of T cells stained with OKTl‐like antibodies. The marrows from the patients with T cell proliferations contain plentiful haemopoietic progenitor cells and it is probable that the T lymphocytes suppress their normal maturation. There was a poor response to splenectomy in 2 patients with T cell proliferations, and single cytotoxic drug therapy may be more appropriate when therapy is required. The literature is reviewed and it is suggested that the T cell proliferations may be secondary to the rheumatoid process.
‘Incomplete’ pyroglobulin‐gamma disease in a patient with osteosclerotic myeloma
Authors: Ruiz‐Arguelles A. , Valls‐de‐Ruiz M. , Dominguez‐Barranco A. , Ruiz‐Arguelles G. , Ruiz‐Reyes G.
Published: August 2010

A 50‐year‐old female, heterozygous for beta‐thalassaemia was found to have a iytic lesion surrounded by osteosclerotic tissue in the 1st lumbar vertebra. Aspiration of the lesion showed 100% atypical plasma cells. The bone marrow contained 17% myeloma cells. Despite normal electrophoresis and immunoelectrophoresis of serum and urine, ‘rouleaux’ formation was pronounced. Treatment of the serum sample with 2‐mercaptoethanol and heat (56°C) disclosed an uncommon pyroglobulin. Analysis of the ammonium sulphate precipitate of the serum by sodium‐dodecyl‐sulphate polyacrylamide gel electrophoresis revealed a 43 kD component with higher anodic mobility than normal gamma chains. Ultrafiltration column chromatography of the serum revealed a narrow spike of approximately 4 S that contained gamma heavy chain antigenic determinants in addition to normal 7 S IgG.—
Expression of spectrin in normal and malignant erythropoiesis
Authors: Ekblom Marja
Published: August 2010

Spectrin is a major constituent of the erythrocyte membranoskeleton. The occurrence of spectrin during normal and malignant erythropoiesis was investigated by immuno‐fluorescence using a monospecific rabbit anti‐human spectrin antiserum. The expression of spectrin was correlated to the presence of glycophorin A, which is an early and specific marker for erythroid cells. The expression of spectrin during normal erythroid differentiation coincided with that of glycophorin A. Both markers were already present in the proerythroblasts. Spectrin was also found in leukaemic cells from patients with acute erythroleukaemia and erythroid blast crisis of chronic myelogenous leukaemia. In a large panel of human haematopoietic cell lines only those with erythroid phenotype (K 562 and HEL) stained positively for spectrin. It is concluded that spectrin appears early in the erythroid maturation. It is expressed both in normal and malignant erythroid precursors. Spectrin can be used as a marker for erythroid blasts in the diagnosis of erythroleukaemias.—
Phenotype of the terminal transferase‐positive cells in human foetal liver and bone‐marrow: Analysis with monoclonal antibodies
Authors: Bonati Antonio , Delia Domenico , Starcich Bruno , Buscaglia Maura
Published: August 2010

Liver and bone‐marrow of 20 human foetuses between 15th and 20th week of gestational age were examined. Mononuclear cells were labelled with murine monoclonal antibodies to reveal surface antigens and with a rabbit antiserum to TdT for the detection of the nuclear enzyme, using a double colour indirect immunofluorescence technique. The results have revealed that TdT+ cells express the phenotype of B cell precursors HLA‐DR+, CALLA+, FMC8+, LEU‐1‐, LEU‐5‐, LEU‐9‐‐. It suggests that foetal liver and bone‐marrow have an active function in B‐lymphopoie‐sis in humans. The involvement of TdT in the process of B‐cell immunological acquisition is uncertain because only humans and Xenopus embryos, among the species examined, express TdT outside the thymus during ontogenesis.
IgM and IgG Platelet Antibodies in a Case of Infectious Mononucleosis and Severe Thrombocytopenia
Authors: Kappers‐Klunne M. C. , van Vliet H. H. D. M.
Published: August 2010

Platelet antibodies of IgG and IgM class were detected in the serum of a patient with infectious mononucleosis and thrombocytopenia. Platelet counts and antiplatelet antibody levels were inversely correlated, but both normalized after complete recovery of the patient.
Centrifugal and anticoagulant induced variations in platelet rich plasma and their influence on platelet aggregation
Authors: HEALY DAVID T. , EGAN ERNEST L.
Published: August 2010

Variations in the centrifugal force (g) used to prepare platelet‐rich‐plasma (PRP) alter not only the number of platelets therein but also their size and reactivity. Anticoagulants also affect these parameters. According we suggest that PRP preparations need to be strictly standardised. Critical comment on the use of the platelet aggregation model as a means of assessing 5‐hydroxytryptamine receptor function is included.
Bone marrow failure in dyskeratosis congenita*
Authors: HANADA TAKASHI , ABE TSUKASA , NAKAZAWA MASAKI , AOKI YASUKO , UYENO KENICHI
Published: August 2010

We report a case of dyskeratosis congenita (DCG) with neutropenia, lymphocytopenia and thrombocytopenia. Peripheral blood T lymphocytes (T cells) were proved to have a suppressive effect on the colony forming unit granulocyte‐macrophage (CFU‐GM). Splenectomy caused a transient increase of neutrophil count with the disappearance of the suppressive T cell activity. However, pancytopenia recurred without re‐appearance of suppressive T cell activity.
Multicentre evaluation of Normotest performance characteristics Interlab variation, comparison of manual and instrumental techniques, reproducibility, normal range
Authors: CISMEL ITALIAN , MANNUCCI P. M.
Published: August 2010

Normotest (NT) is a standardized reagent sensitive to changes in concentration of factors II, VII and X. It has been proposed as a useful screen for the liver synthetic function. We carried out a multicentre study aimed to compare in 5 different labs variability and reproducibility of results, normal ranges and manual versus instrumental techniques. NT values were significantly different in the 5 labs, regardless of how the results were expressed. However, within each lab, the results of manual and instrumental techniques were usually not different, providing they were expressed as ratios of test to reference plasmas. Within‐lab, between‐day reproducibility was much greater when results were expressed as ratios than as %s; reproducibility was also greater with the instrumental than with the manual technique. With both techniques, normal ranges established in each lab were much more uniform when the results were expressed as ratios than as %s. On the whole, this study suggests that NT results should be expressed as ratios, that instrumental techniques should be preferred to manual techniques, and that each lab should establish its own normal range.
Serum ferritin in Danish children and adolescents
Authors: Milman Nils , Ibsen Karsten Kaas
Published: August 2010

Serum ferritin concentrations were measured in 909 urban Danish schoolchildren (451 boys, 458 girls) 6 to 17 years old. The children had been randomly selected and served as an urban reference population. Geometric mean ferritin values were identical in boys and girls 6 to 15 years old, while 16‐ and 17‐year‐old boys had higher values than girls (P < 0.01). There was a slight rise in mean ferritin values from 6 to 11 years, followed by a temporary fall during the subsequent adolescent growth period. Geometric mean ferritin values and significant differences were as follows: Children 6 to 11 years old (n = 335), 29 μg/l and adolescents 12 to 15 years old (n = 417), 26 μg/l (P < 0.01): Adolescent boys 16 to 17 years old (n = 76), 32 μg/l and adolescent girls same age (n = 81), 24 μg/l (P < 0.01). The frequencies of low ferritin values < 10 μg/l (i.e. exhausted iron stores) were: Children 6 to 11 years old, 2.1%: Adolescents 12 to 15 years old, 5.0%: Adolescent boys 16 to 17 years old, 0.0%: Adolescent girls 16 to 17 years old, 11.1%. High ferritin values > 60 μg/l (i.e. large iron reserves) were observed in 6.2% of boys and 6.9% of girls.
Acquired factor VIII:C inhibitor (IgG) and positive direct Coombs' test (IgM) in a patient with lung carcinoma
Authors: de Cataldo F. , Baudo F. , Redaelli R. , Pezzetti L.
Published: August 2010

A 73‐year‐old man with lung squamous‐cell carcinoma simultaneously developed a factor VIII:C inhibitor and a transient positive direct Coombs' test. The factor VIII:C inhibitor was characterized as a mixture of IgG1, IgG2, IgG4 with χ and Λ light chains. The Coombs' test was IgM‐specific.

Treatment: blood transfusions (packed red cells), cyclophosphamide and prednisone. Bleeding subsided without factor VIII‐replacement therapy. Before death, in spite of the tumour‐mass progression, factor VIII:C was normal.
PHM 14: A novel monoclonal antibody that reacts with both normal and neoplastic human B cells but not B‐CLL
Authors: Barr I. G. , Hancock W. W. , Kraft N. , Toh B. H. , Atkins R. C.
Published: August 2010

The reactivity of PHM 14, a monoclonal antibody to B cells produced in our laboratory was compared with Leu 10, a commercially produced antibody. Flow microfluorometric analysis showed that both PHM 14 and Leu 10 reacted with normal B cells, a variety of B cell lines and with B cell leukaemias and lymphomas, except in the case of B‐CLL where PHM 14 reacted with a minority of cases, whereas Leu 10 reacted with a majority. PHM 14 and Leu 10 did not react with normal monocytes, granulocytes, T cells, T cell lines or with T cell leukaemias or lymphomas. Specificity of PHM 14 for B cells was further supported by the demonstration that PHM 14‐positive blood cells, sorted from PHM 14‐negative blood cells, reacted with polyclonal anti‐immunoglobulins and with a panel of B cell markers but did not react with markers for T cells, monocytes, granulocytes or NK cells. Our results suggest that both PHM 14 and Leu 10 should be useful diagnostic reagents in the investigation of B cell‐derived leukaemias and lymphomas.
Evolution of antithrombin III during the postoperative period
Authors: Rodzynek Jean‐Jacques , Leautaud Pierre , Damien Jacqueline , Rosa Marie‐Pierre , Govaerts Jean‐Paul
Published: August 2010

In a prospective study, antithrombin III (AT III) was performed preoperatively, peroperatively immediately after the surgical procedure and daily during the 8 postoperative days in 57 consecutive patients who underwent major abdominal surgery without prophylactic anticoagulant therapy. On d 8, according to the results of a bilateral radiological phlebography, the patients were divided into 2 groups: Group I: presence of deep venous thrombosis (DVT): n = 28 (49%) and Group 2: absence of deep venous thrombosis: n = 29 (52%). The results of the study showed that the preoperative AT III value did not constitute a marker of the postoperative DVT risk. During the postoperative period, AT III level decreased immediately following the intervention and resumed its preoperative value within 8 d. Nevertheless, this evolution was not different in the 2 groups and was not related to the presence of postoperative DVT.
Differences in phagocytic/adherence properties between normal neutrophils
Authors: Stavem Per , Dahl Ove
Published: August 2010

Neutrophils, serum opsonins and staphylococci were incubated at 37° C with continuous end‐over‐end rotation. The observed frequency of neutrophils with 0, 1, 2… staphylococci deviated systematically from that expected for a Poisson distribution. This suggests marked differences in phagocytosis/adherence between the neutrophils, indicating different neutrophil populations.
Heparin and Factor VIII
Authors: Sibinga C Th Smit , Das P C
Published: August 2010

New approaches and techniques for improving source material collection and factor VIII production at Blood Bank level have been reported recently. Heparin has shown to be of great importance in increasing both yield and stability of factor VIII in the purification and concentration process. Work has been done to develop on a routine scale a heparin double cold‐precipitation technique for the production of freeze‐dried high yield purified factor VIII concentrate. As a spin‐off of the method red cell concentrate (RCC) and cryosupernatant plasma (SDP), both containing small amounts of heparin besides the standard CPDA‐1 anticoagulant, are recovered for clinical use. Results of the tests done:

RCC ‐ in vitro: Normal Adenosin Tri‐Phosphate (ATP), 2 3 Di‐Phospho‐Glycerate (DPG) and shelf‐life, Heparin 0.7 IU/ml (±0.3).

‐ in vivo: Normal half 51Cr‐survival, no side effects.

SDP ‐ in vitro: Protein and chemical analysis normal, shelf‐life normal, Heparin 3.5 IU/ml (±0.7).

‐ in vivo: No side‐effects, mild effect on activated Partial Thromboplastin Time (aPTT) 5 minutes post transfusion.

Factor VIII concentrate ‐ in vitro: Yield 56.2 (±8.2) percent, purity 0.8 (±0.15) FVIII:C IU/mg protein, potency 25.2 (±3.2), FVIII:C IU/ml Heparin 6.2 (±0.7) IU/ml.

‐ in vivo: Normal recoveries and half‐lifes after injection of 15–20 IU/kg in 4 severe hemophilia A patients.

This heparin small pool high yield principle is expected to have great impact on availability, access to and safety of adequate treatment in hemophilia in the future.
International and National Standards for Factor VIII
Authors: Barrowcliffe T. W.
Published: August 2010

Reference standards for factor VIII are necessary because of the wide variation of factor VIII:C in normal plasma and its instability. A stable freeze‐dried concentrate was established as the 1st International Standard by comparison with fresh normal plasma in many laboratories. Replacement standards have since been calibrated against the previous standards and also compared with average normal plasma collected from large numbers of donors. National standards have been established in several countries and have existed for many years in the U.K. and U.S.A. These are calibrated against the international standard in collaborative studies. Concentrate standards should be used for assay of therapeutic concentrates. Plasma standards are most appropriate for patients' plasma samples, and calibration of these against the international standard concentrate has led to discrepancies between laboratories and between assay methods. An international reference preparation of factor VIII plasma has therefore been established, and this has been calibrated for other VIII‐related activities as well as VIII:C.
Markers for the Factor VIII Antibody Response in Hemophilia A
Authors: Shapiro S S
Published: August 2010

Antibodies to FVIIIC occur in 5‐5 percent of patients with hemophilia A who receive FVIII replacement therapy. Several observations suggest that the immune response to FVIIIC may be under some form of genetic control. The American Cooperative Study of FVIIIC inhibitors in hemophilia A has followed 1,522 patients with hemophilia A and has examined a number of variables relating to this problem. Antibodies were present in 216 patients at entry into the study and an additional 31 patients developed antibodies during the study. Almost all antibodies occurred in patients whose FVIIIC was < 0.03 U/ml. One quarter of the antibody patients had low‐titer antibodies despite repeated treatment, although an occasional low‐ttter antibody eventually converted to high‐titer. Among the 31 patients who developed antibodies during the study, 15 were high‐titer (>10 Bethesda U/ml) and all but 3 developed within the first 100 exposure‐days to FVIII. Studies of 167 sibships with at least 2 hemophilic brothers showed a non‐random distribution of antibodies. HLA typing of 35 antibody and 105 non‐antibody patients showed an under‐representation of HLA‐Al in antibody patients. We also studied polymorphisms of complement components C2, C4A, C4B and factor B, known to be synthesized under genetic control of loci on chromosome 6, close to the HLA‐Dr locus. The frequencies of C4A4, C4B2 and factor BF‐F were 1‐1/2 to 2 times higher in antibody formers than in non‐antibody patients. Taken together, these studies imply strongly the presence of some Immune Response gene control over the FVIIIC antibody response in patients with hemophilia A.
Acquired Immunodeficiency Syndrome (AIDS) in Hemophiliacs
Authors: Jason J M , Evatt B L , Chorba T L , Ramsey R B
Published: August 2010

From mid‐1977 to mid‐1983 the Centers for Disease Control (CDC) has received reports of more than 2,100 cases of acquired immunodeficiency syndrome (AIDS). These cases had either biopsy confirmed Kaposi's sarcoma or a biopsy or culture confirmed life‐threatening opportunistic infection, without an identifiable cause of immunosuppression. Reports of AIDS in hemophiliacs began to appear in January 1982. As of October 6, 1983, CDC has confirmed 18 reports of AIDS in United States (U.S.) hemophiliacs and 5 outside the U.S. Two had other known risk factors for AIDS. Seventeen of these cases had Pneumocystis carinii pneumonia. (PCP). The mortality rate for the 23 hemophiliac cases was 70 percent. Immunologic findings included lymphopenia, a decreased ratio of T helper/T suppressor lymphocytes, and hypergammaglobulinemia. Most hemophiliac cases did not reside in areas of high risk for AIDS. All cases had received factor and, often, other blood products in the 5 years prior to the AIDS diagnosis. The racial distribution of hemophiliac AIDS patients resembled that of transfusion‐associated AIDS patients. Hemophiliac AIDS patients resembled both transfusion‐associated and IV‐drug abuser AIDS patients and differed from homosexuals with AIDS in regard to associated diagnoses. The epidemiology of these cases is consistent with the possibility that AIDS is caused by an agent transmissible through blood products. These data support the need for current blood product related precautions issued by the National Hemophilia Foundation and by the Public Health Service.
AIDS and Immunologic Abnormalities In European and American Hemophiliacs
Authors: Green D
Published: August 2010

Reports of acquired immunodeficiency syndrome (AIDS) in U S hemophiliacs prompted us to survey European Hemophilia Centers to determine the frequency of AIDS and other disorders of immunity. Data was obtained from 29 Hemophilia Centers in 15 countries, representing 4,310 hemophilic patients. Therapeutic concentrates, of local and commercial origin, had been in use in these Centers for an average of 12 years (range 5–25 years). Despite this long exposure, only 5 possible cases of AIDS were identified, and a few of these did not strictly fulfill the criteria for diagnosis established by the U S Centers for Disease Control. Five cases of thrombocytopenia were also reported. An examination of 35 patients enrolled in our own Hemophilia Center disclosed one case of immune thrombocytopenic purpura, and 24 of the 35 (68 percent) with reversal of the T4/T8 ratio. We conclude that while disturbances of immunoregulation are common in hemophilia, to date classical AIDS has appeared infrequently.
The Role of a National Organization in the AIDS Issue
Authors: Carman C J
Published: August 2010

A national hemophilia society can play key roles in addressing issues concerning AIDS. The National Hemophilia Foundation (NHF), U.S.A., has put together an organization which enables it to interface quickly and with a consistent message to a variety of groups concerned with AIDS. Issues addressed included recommendations to patients, families, treaters, and the blood and plasma fractionation industry. In addition, the NHF served as a source of consistent information for the news media and for government agencies. This paper describes the organization and administrative procedures used to ensure a national voice representing the best interest of those affected by hemophilia during this period of concern over AIDS. The NHF model relied heavily upon its national medical and scientific resources. This assured that NHF constituents were being represented by a broad view rather than by a narrow view.
A Scheme for the Future
Authors: Sibinga C. Th. Smit
Published: August 2010

For hemophilia care on an equitable basis all over the world, adequate treatment should comprise to complex of:

Sufficient quantities of finished products, starting from 20,000 IU of factor VIII per patient per annum, to ensure a basic standard and comfort of life.

Acceptable qualities of preparations, to protect the patient from unnecessary and unwarranted risks of infection and compromittance of immunity.

Environment of treatment provided through comprehensively organized treatment centres.

Social acceptance to better balance the costs and benefits, primarily in humanitarian terms.

It is concluded that the protection against transmittable disease is suspected to be limited, either by returning to the small pool concept or applying physico‐chemical principles such as heat treatment or other approaches.
STANDARDIZATION OF VIII:C ASSAYS: A MANUFACTURER'S VIEW
Authors: Mikaelsson Marianne , Oswaldsson Ulla
Published: August 2010

ABSTRACT:  Despite the use of an International Standard to define the unitage of Factor VIII coagulant activity (VIII:C) discrepancies still exist with respect to labelled potencies. In order to examine possible causes of this disagreement concentrates of low, intermediate and high purity, normal plasma (NP) and the 1st International Reference Plasma (IRP) were assayed against the 3rd International Standard (IS) using one‐stage, two‐stage and chromogenic substrate assays.

When different concentrates were estimated in relation to the 3rd IS, and NP in relation to the 1st IRP, there was good agreement between the potency estimates obtained by the different assay methods. Consistent results were obtained when VIII:C deficient plasma was used instead of buffer as prediluent. When NP and IRP were assayed against the 3rd IS marked differences between the assay methods were observed when buffer was used as prediluent. This effect was reduced when the 3rd IS was prediluted with VIII:C deficient plasma.

Many factors influence the standardization of VIII:C assays, but good agreement between methods can be achieved provided that like preparations are compared under standardized conditions.
IN VIVO RECOVERY OF FVIII:C IN HEMOPHILIC PATIENTS
Authors: Kasper Carol K.
Published: August 2010

ABSTRACT:  Average pre‐operative in vivo recoveries of factor VIII:C concentrate fell from 1967 to 1976, then improved, and fell again in the early 1980's. Average outpatient in vivo recoveries were studied from 1978‐83; the lowest values for two of three brands were seen in 1980. Standard in vivo recovery studies were performed with a 10 minute post‐infusion plasma sample only, but detailed tests in 39 patients indicated that the peak post‐infusion level after concentrate infusion occurred at 30 minutes rather than 10 minutes in 23 percent of recipients. Comparison of one‐ and two‐stage assay methods showed that higher in vivo recoveries were obtained when plasma samples were assayed with the two‐stage method. The major cause of discrepancies between observed and expected VIII:C recoveries, however, is believed to be inaccurate assessment of the VIII:C potency of various in‐house VIII:C references. Methods of in vitro assay of concentrates which adequately predict in vivo effect are needed.
A possible pathogenetic role of cationic proteins (CP) released by stored granulocytes in the development of pulmonary infiltrates after granulocyte transfusions
Authors: Campana D. , Camussi G. , Bergui L. , Vallauri P. , Tesio L. , Tetta C. , Caligaris‐Cappio F.
Published: August 2010

The cationic protein (CP) content of polymorphonuclear neutrophils (PMN) prepared for transfusion is depleted after storage. The supernatants from these PMN have in vitro a PMN aggregating activity which is abolished by the preabsorption with a specific rabbit anti‐human PMN CP serum. Furthermore, when the supernatants stored for few hours were injected into New Zealand White rabbits, a marked sequestration of PMN took place in the lung microvascular bed. It is suggested that PMN storage per se can cause the release of intracellular mediators of possible pathogenetic importance in the development of the pulmonary infiltrates observed after PMN transfusions.
Role of S‐adenosylmethionine in DNA synthesis and haemopoiesis
Authors: Sourial N.A. , Amess J.A.L. , Amos R.J.
Published: August 2010

In man, exposure to nitrous oxide (N2O) can produce neurological damage and megaloblastic change in the bone marrow due to inactivation of vitamin B12. Methionine metabolism is interrelated with that of vitamin B12 and folate; the effect of methionine on the impaired DNA synthesis produced by N2O was therefore studied in 17 patients undergoing surgery. 14 were anaesthetised with 50% N2O in oxygen for 3–24 h. The remaining 3 had been exposed to N2O for less than 3 h. All patients developed megaloblastic bone marrow change except 2 of the latter patients whose bone marrows remained normoblastic.

The bone marrow was studied biochemically using the deoxyuridine (dU) suppression test. The in vitro addition of small doses of methionine was as effective as vitamin B12 itself in correcting the defective DNA synthesis produced by N2O. It is suggested that N2O impairs methionine biosynthesis, methionine, in the form of S‐adenosylmethionine (SAM), being required for DNA synthesis and the prevention of the development of megaloblastic anaemia in man.
Kinetics of 111In‐labelled platelets in healthy subjects
Authors: Schmidt Kai Gjerløff , Rasmussen Jens Wæver , Rasmussen Anker Dahl
Published: August 2010

25 healthy subjects underwent platelet kinetic and scintigraphic studies following injection of 111In‐labelled platelets. Using the multiple hit model, platelet mean lifetime averaged 185.3 hours (range 141.2–225.6), and platelet in vivo recovery averaged 56 % (range 42–89). The platelet disappearance pattern was almost linear. However, in comparison with simultaneously injected 51Cr‐labelled platelets (7 subjects studied), the 111In‐platelet survival curves were slightly more curved. Our results indicate that this may be ascribed to a slight degree of elution of 111In from the circulating platelets. The plateau or even slight increase in circulating activity following the initial steep decline in activity appears mainly to reflect reversible sequestration of platelets in the spleen and maybe in the liver. Using a semiquantitative scintigraphic approach, we estimated 45 %, 25 % and 30 % platelet destruction to occur in the spleen, liver and bone marrow, respectively. Our results indicate that the discrepancy between the course of circulating platelet‐bound activity and of chest wall activity reflects platelet destruction in the bone marrow.
Combined factor V and factor VIII deficiency with normal protein C and protein C inhibitor. A family study
Authors: Adam Khalifa A. Rahim , Seed Fath Al Rahman A. El , Karrar Zein A. , Gader A.M.A.
Published: August 2010

Combined deficiency of factor V and factor VIII, a rare bleeding disorder, is reported in a Syrian family. 2 siblings, 10 and 6 yr old are affected. They had mild bleeding manifestations. Their prothrombin time and partial thromboplastin time were prolonged, but thrombin time was normal. Both had low levels of factor V, (6% and 7%), factor VIII, (both 10%) factor VCAg (both 6 %) and factor VIII CAg, (6% and 4%). All members of this family had normal levels of factor VIIIR:Ag, protein C antigen and protein C inhibitor. The normal levels of protein C and protein C inhibitor in the 2 affected family members indicate that the combined deficiency of factors V and VIII has nothing to do with protein C. This contrasts with previous reports that deficiency of protein C inhibitor is the cause of combined factor V and factor VIII deficiency. The probable mode of inheritance of this defect is discussed.
Occurrence of HTLV‐I antibodies in Danish patients with cutaneous T‐cell lymphoma
Authors: Saxinger W. Carl , Wantzin Gunhild Lange , Thomsen Kristian , Hoh Mei , Gallo Robert C.
Published: August 2010

10 of 68 CTCL (cutaneous T‐cell lymphoma) patients without features of ATLL had antibodies against HTLV‐I (human T‐cell leukaemia virus, type I). The titre of antibody in these positive patients was generally much lower than that seen in cases of ATLL (adult T‐cell leukaemia/lymphoma); geometric mean of 80 for CTCL vs. 8000 for Caribbean ATLL. The presence of HTLV‐I antibody was unrelated to clinical remission, relapse, or stages of the disease, and some positives were detected in the earliest phases of mycosis fungoides. Among controls and normal donors between the ages of 40 and 65, only 1 of 36 and 3 of 113, respectively, had low titre antibodies to HTLV‐I in their sera. Only 5 of 354 Danish normal donors of all ages had antibody, which was identical to the rate in over 2000 US normal donors. In negative control experiments, these antibodies were unreactive with bovine leukaemia virus. These data suggest that HTLV‐I or a related retrovirus crossreactive with HTLV‐I occurs in a low percentage of the Danish population and patients with CTCL have such antibodies at an increased rate, but less than the rate seen for ATLL (> 90%).
Survival in 222 adult patients with acute leukaemia treated with intermittent combination chemotherapy programme
Authors: Evensen S.A. , Stavem P. , Lund E.
Published: August 2010

222 patients aged 15–59 years with acute leukaemia were treated with intermittent combination chemotherapy consisting of six 5‐day courses of cytotoxic drugs as induction treatment followed by 3 years of maintenance therapy in patients who obtained complete remission (CR). CR was achieved in 50.3% of 161 patients (early deaths included) with acute myelogenous leukaemia (AML). The observed cumulative 5‐yr survival rate (observation time 1–12.25 yr) calculated by the life table method was 12% in AML. Among patients who obtained CR, those aged 40–59 yr appeared to fare better than younger patients (5‐yr survival: 24%). The M‐3 subtype was an adverse prognostic factor. In acute lymphoblastic leukaemia (ALL) the CR rate was 83.6% and the observed cumulative 5‐yr survival rate was 14%. Women fared better than men.
Globin chain synthesis in a case of acquired aplastic anaemia before and after remission induced by bolus methylprednisolone treatment
Authors: Özsoylu Sinasi , Gürgey Aytemiz
Published: August 2010

Globin chain synthesis was performed with the peripheral blood of a 10‐year‐old girl, who had acquired aplastic anaemia, at the time of bolus methylprednisolone administration and during recovery. There was no indication of an increase in γ chain synthesis despite elevation of total foetal haemoglobin.
Naproxen has greater antipyretic effect on Hodgkin's disease‐related fever than on other tumours or infection
Authors: Geisler C. , Gøtzche P. C. , Hansen S. Schade , Juul K. , Plesner A. M. , Nissen N. I.
Published: August 2010

In 28 febrile patients with malignant lymphoma or leukaemia, the hourly temperatures were recorded following an oral dose of 125 mg naproxen (50% of normal single adult analgesic dose). 15 patients had clinical infection, and 13 had fever secondary to their malignant disease. Compared to controls, there was no significant antipyretic effect of 125 mg naproxen in infected patients, whereas this small dose in patients without infection had a significant effect. In the uninfected patients, the antipyretic effect was significantly more marked in fever related to Hodgkin's disease than to non‐Hodgkin lymphoma or leukaemia. This selective antipyretic effect of a prostaglandin‐synthesis inhibitor in turnour‐related fever, especially in Hodgkin's disease, is unexplained but may be useful in the palliative treatment of patients with advanced disease.
Treatment of severe chronic idiopathic thrombocytopenic purpura in adults with high‐dose intravenous gammaglobulin
Authors: Korninger C. , Panzer S. , Graninger W. , Neumann E. , Niessner H. , Lechner K. , Deutsch E.
Published: August 2010

12 patients with severe chronic idiopathic thrombocytopenic purpura (ITP) were treated with i.v. polyvalent intact immunoglublin (0.14–0.4 g/kg body weight for 5 d) because of various bleeding episodes or prior to surgery. In 9 patients a significant rise in platelet counts was noted, starting on d 2 and reaching its maximum between d 4 and 11. Thereafter, platelet counts decreased slowly, approaching pre‐treatment values after 20 d in most cases. Response to immunoglobulin was reproducible, when infusions were repeated. Response to high‐dose immunoglobulin was independent of age of patients and duration of disease. Platelet‐associated IgG decreased in all patients tested. A pepsin‐treated immunoglublin preparation was ineffective in 3 patients.
Megakaryocyte differentiation capacity of human pluripotent bone marrow progenitor cells CFU‐GEMM in vitro after cryopreservation*
Authors: Ganser A. , Hoelzer D.
Published: August 2010

The effect of cryopreservation on the pluripotent haemopoietic progenitors CFU‐GEMM as well as on the megakaryocyte (CFU‐Mk), erythroid (BFU‐E) and granulocytic‐monocytic (CFU‐GM) progenitor cells was analyzed. Progenitor cell recovery after freezing, as determined in 5 experiments, averaged 89% for CFU‐GEMM (range: 63% ‐ 194%), 85% for CFU‐Mk (range: 62% ‐ 96%), 92% for BFU‐E (range: 43% ‐ 174%) and 60% for CFU‐GM (range: 31% ‐ 93%). Immunological analysis of individual mixed colonies using a double labelling immunoalkaline phosphatase slide technique and monoclonal antibodies against megakaryocytic and granulocytic cells revealed megakaryocyte cells in more than 79% (range: 73% ‐ 94%) and 84% (range: 75% ‐ 87%) of mixed colonies before and after freezing, respectively. Our results indicate that cryopreservation of human bone marrow cells does not alter the megakaryocytic differentiation capacity of the haemopoietic progenitor cells CFU‐GEMM and CFU‐Mk in vitro.
Granulocytic and stromal progenitors in the bone marrow of patients with primary myelofibrosis
Authors: Hotta Tomomitsu , Utsumi Makoto , Katoh Taiji , Maeda Hideaki , Yamao Hisami , Yamada Hideo
Published: August 2010

Quantitative and qualitative changes in granulocyte‐macrophage (CFU‐GM) and fibroblast colony‐forming cells (CFU‐F) were studied in 7 patients with primary myelofibrosis (MF). Marrow cells were collected from bone biopsy specimens after treatment with collagenase. The number of CFU‐GM correlated with the amount of haemopoietic tissue noted in the bone marrow histology and ranged between 0–400/mg of bone. CFU‐F were increased in 2 patients with moderate fibrosis. Circulating CFU‐GM were increased in all patients studied (169–3749/ml of blood). There was no significant correlation between the number of CFU‐GM in the bone marrow and that in the blood. Cytochemical studies showed a high incidence in eosinophil progenitors in the bone marrow and especially in the blood of patients with MF. These data suggest a functional abnormality of myeloid progenitors in this disease.
Combined study of lymphocyte phosphoglucomutase (PGM) and adenylate kinase (AK) isoenzymes in the early characterization of bone marrow engraftment
Authors: Corrons J. L. Vives , Merino A. , Pujades A. , Gran̄ena A. , Carreras E. , Marin P. , Rozman C.
Published: August 2010

A starch‐gel electrophoretic study of 2 peripheral blood lymphocyte enzymes, phosphoglucomutase (PGM) and adenylate kinase (AK), was performed in 25 donorrecipient allogenic bone marrow transplantation (BMT) pairs. A different isoenzymatic pattern between donor and recipient for PGM, AK or both, was observed in 11 of these 25 pairs. From these 11 cases, an identical donor isoenzyme pattern was observed in 10 cases between 24 and 85 days (mean 41.8, SD 22.08) after BM infusion confirming engraftment, whereas in the remaining 1 the demonstration could not be substantiated due to early death. The present study demonstrates that, in addition to other cell markers, the simultaneous study of PGM and AK isoenzymes allows confirmation of BM engraftment in about 45% of cases, much earlier than is possible by means of red cell antigen analysis. Moreover, it is a simple, relatively inexpensive and rapid laboratory tool for a better characterization of the established chimera.
Decreased red cell deformability and vascular obstruction in falciparum malaria illustrated by a fatal case
Authors: Ahlqvist Johan
Published: August 2010

The autopsy findings in a case of falciparum malaria suggested that rheological mechanisms, above all decreased deformability of red cells, might have been the main cause of capillary obstruction. This mechanism had been assumed to be involved already in 1972, and red cells containing mature parasites have recently been shown to lack deformability. This may explain why severe cases have recovered after blood exchange.
Successful treatment of acute megakaryoblastic leukaemia
Authors: Ninomiya Haruhiko , Nakazawa Masaki , Shibuya Akira , Aoki Yasuko , Nagasawa Toshiro , Abe Tsukasa
Published: August 2010

2 patients with acute megakaryoblastic leukaemia (AMKBL) were successfully treated with a combination of aclarubicin hydrochloride (an anthracyline), enocitabine (a derivative of cytosine arabinoside) and 6‐mercaptopurine (6‐MP) or 6‐thioguanine (6‐TG). They achieved a complete remission following 1 or 2 courses. They remained well and in complete remission throughout 3 courses of consolidation therapy, a total of 9 weeks.

The results of remission induction therapy of AMKBL have been reviewed in the literature. 4 of 7 adult patients, including our cases, treated with 3 drugs, anthracycline, cytosine arabinoside or its derivative and 6‐TG or 6‐MP, achieved a complete remission. AMKBL may not have so poor a prognosis as previously believed.
Increased binding to ADP‐stimulated platelets and aggregation effect of the dysfibrinogen Oslo I as compared with normal fibrinogen
Authors: Thorsen L. I. , Brosstad F. , Solum N. O. , Stormorken H.
Published: August 2010

Interactions of the dysfibrinogen Oslo I with platelets were investigated. This fibrinogen is a Bβ‐chain variant with faster than normal fibrin monomer polymerization. Fibrinogen Oslo I acted more efficiently in ADP‐induced platelet aggregation, and bound to gel‐filtered platelets with a higher affinity constant than did normal fibrinogen. At all concentrations more fibrinogen molecules became bound per platelet with the dysfibrinogen than with normal fibrinogen, both when the fibrinogens were tested separately or as a mixture using 125I or 131I to label the two types. At high concentrations this was probably due to ligand polymerization of the dysfibrinogen. These observations indicate that the increased cofactor function in platelet aggregation may be related to the increased affinity of the dysfibrinogen for the platelets.
Heme synthesis in sideroblastic anaemias
Authors: Pasanen Aarne , Tenhunen Raimo
Published: August 2010

The underlying biochemical abnormalities common to all forms of sideroblastic anaemia appear to be associated with impaired heme synthesis in erythroid precursors. Present knowledge on the specific enzymatic defects of heme synthesis, which are thought to be the basis for the ring sideroblast abnormality, is presented in this review. Different forms of sideroblastic anaemia have different enzyme defects, but some of them might be secondary due to inhibition by mitochondrial iron overload. Some drugs and toxins may suppress heme synthesis and cause a reversible sideroblastic anaemia. Recent experimental studies have also provided detailed biochemical explanations for cases responding to pyridoxine therapy. Leukaemic transformation, which occurs in some cases of idiopathic sideroblastic anaemia, is not predictable on the basis of any abnormality of heme synthesis, but further impairment of heme synthesis seems to accompany the leukaemic development in such patients. So far, no association between the chromosomal aberrations and the defects of heme synthetic enzymes has been found.