bluuebunny/crossref_metadata_2025 huggingface dataset:
High dose intravenous glucocorticoid in the treatment of childhood acquired aplastic anaemia
Authors: Özsoylu Şinasi , Coşkun Turgay , Minassazi Şemsettin
Published: August 2010

31 children with acute acquired aplastic anaemia were treated with very high doses of i.v. bolus methylprednisolone. In 3 of them, paroxysmal nocturnal haemoglobinuria was diagnosed. Therefore the responses of 28 patients have been evaluated. Normo‐blastaemia and reticulocytes were observed on about the 6th d and leucocyte and granulocyte response around the 11th d of treatment. The first haemoglobin (≥ 0.5 g/dl) and haematocrit elevations were documented on about the 16th d and the initial platelet response (average ≥ 34 times 109/1) took more than a month. At least 64% of the patients responded to this treatment including 2 cases in whom aplasia was observed following hepatitis. Although 10 episodes of recurrences occurred in 8 patients (with the exception of 3 patients’ in whow 5 recurrences were observed), response to the same regimen was obtained. With 1 exception the side‐effects of this treatment could be managed by decreasing the dose. With this treatment, acquired aplastic anaemia should no longer be considered a fatal disease, at least in children.
Mediterranean glucose 6‐phosphate dehydrogenase (G6PD) deficiency – Near normal decay of the mutant enzyme protein in circulating erythrocytes
Authors: Morelli Alessandro , Benatti Umberto , Guida Lucrezia , De Flora Antonio
Published: August 2010

Complete removal of leucocytes and platelets from erythrocytes and the development of a sensitized procedure for the assay of G6PD activity allowed the biochemical mechanisms of the Mediterranean variety of G6PD deficiency to be re‐evaluated. Activity in the young erythrocytes from 9 G6PD‐deficient subjects averaged 0.1% of the levels observed in the corresponding erythrocyte fraction from normal individuals: moreover, the decline of activity during aging of the G6PD‐deficient erythrocytes was comparable with that observed for the normal enzyme. Mutant G6PD purified from granulocytes of a G6PD‐deficient subject and entrapped within the corresponding erythrocytes was remarkably stable. Exposure of native erythrocytes to an oxidative stress (divicine plus ascorbate) resulted in a decrease of G6PD activity that was significantly more rapid and extensive in control than in G6PD‐deficient cells. These results seem to exclude enhanced intracellular breakdown of the mutant protein within the circulating erythrocytes.
Effect on platelet aggregation of oral administration of 10 non‐steroidal analgesics to humans
Authors: Cronberg S. , Wallmark E. , Söderberg I.
Published: August 2010

Platelet aggregation was investigated in platelet‐rich plasma from normal volunteers before and at various times after intake of 10 analgesic drugs. The drugs used were aspirin, piroxicam, naproxen, indomethacin, diclofenac, ibuprofen, diflunisal, paracetamol and oxyphenbutazone. Aggregation of the platelets was induced by adrenaline or ADP and the first and second waves of aggregation were evaluated. It was found that no drug exerted any effect on the first wave of aggregation. The second wave of aggregation was abolished by aspirin that produced a long‐lasting effect for 5–8 d. Piroxicam also abolished the second wave of aggregation and this effect persisted on the 2 following d. Naproxen was normalized in half of the volunteers on the 2nd d. The inhibition caused by indomethacin and diclofenac was corrected on the 2nd d. Ibuprofen and diflunisal produced a definite but short‐term effect. The effect of salicylic acid was weak. Paracematol and oxyphenbutazone did not affect platelet aggregation.
Acute leukaemia in a defined geographic area – Incidence, clinical history and prognosis
Authors: Öst Å. , Lindström P. , Christensson B. , Gyllenhammar H. , Engstedt L.
Published: August 2010

A consecutive series of patients (1978–1981) comprising all patients with acute leukaemia from a population of 475000 inhabitants was reviewed. Thus, 94 patients were diagnosed as having acute leukaemia. No patients were lost from follow‐up. The incidence figures of ALL and AML differed significantly from those of Sweden as a whole. 9 patients were < 15 years old. The median age of adult patients was 64 years, 60.8% being ≥ 60 years old.

Of adult patients with AML, 20% had a preleukaemic history (chronic myeloproliferative disorders, myelodysplastic syndromes and others). None of 6 patients with leukaemia as a metamorphosis of a chronic myeloproliferative disorder achieved a complete remission. The overall remission rate of the remaining adult patients was 25%. Treated patients, 15–39 years old, with AML without any preleukaemic history, had a complete remission rate of 80% compared to 12% for patients ≥ 60 years old with the same diagnosis.

Of 60 patients with ‘primary’ AML, 14 were not treated, mainly because of advanced age and complicating diseases. Most of these patients died within a week of admission.
Haemostatic studies in osteogenesis imperfecta
Authors: Evensen S. A. , Myhre L. , Stormorken H.
Published: August 2010

Two‐thirds of osteogenesis imperfecta (OI) patients claimed that they bruised easily. We have studied haemostasis in 58 subjects with OI, tarda type. The most frequent abnormalities were increased capillary fragility (35%), decreased platelet retention (33%) and reduced factor VIII R:Ag (23%). Reduced ristocetin cofactor, deficient platelet aggregation induced by collagen and prolonged bleeding time were less common findings. The combination of vascular, platelet related and plasmatic defects may reflect that OI is a heterogenous group of disorders with common clinical expression. The tourniquet test is the most valuable screening test of the haemostatic defects observed in OI.
High dose intravenous gammaglobulin and platelet transfusions in leukaemic HLA‐immunized patients
Authors: Bierling P. , Cordonnier C. , Rodet M. , Vernant J. P. , Pesce A. , Rochant H. , Duedari N.
Published: August 2010

3 aplastic patients with acute leukaemia, strongly HLA‐immunized and refractory to platelet transfusions, received polyvalent gammaglobulin i.v. infusions (0.4 g/kg/d for 5 or 6 d) in association with daily random platelet transfusions. Platelet recovery was obtained in 2 patients. The 3rd patient did not show any significant rise in platelet count. The ability of gammaglobulin to prolong the life‐span of incompatible transfused platelets could facilitate the management of HLA‐immunized patients.
Hemophilia — Psychological Factors and Comprehensive Management
Authors: Agle D P
Published: August 2010

Since chronic disease compounds the difficulties of child rearing and increases the incidence of psychological problems in all age groups, patient care emphasizing technology alone is inadequate. Instead, a biopsychosocial approach is necessary to correlate medical care with vital information about the patient's psychological and social state. Hemophilia acts as a chronic recurrent stress on the individual and his family requiring the development of coping behaviors for adaptation. While many hemophiliacs achieve normal psychological development, some are overwhelmed by the illness contributing to maladaptation and a variety of psychological disorders. Accordingly, medical staff efforts and attitudes that promote effective coping are a vital part of comprehensive care. The goals of coping include carrying out acceptable life goals despite illness handicaps, keeping uncomfortable feelings within manageable limits and the maintenance of a positive self‐image. Efforts to support effective coping begin with effective medical care including adequate relief for acute pain, educational programs that promote optimal child rearing and self‐care and the opportunity for the patient and family to talk about concerns and feelings. Comprehensive care also provides for the identification and specific treatment of psychiatric disorders that may develop.
Improving Yield in the Manufacture of Factor VIII Concentrates
Authors: Foster P R , Dickson A J , Dickson I H
Published: August 2010

Although a number of different processes are used to prepare factor VIII concentrates from human plasma the recovery of coagulant activity is almost always very low.

A number of loss mechanisms can be identified and these tend to be associated with large‐scale manufacture, where pools of hundreds or thousands of litres of plasma are processed. Many of the procedures which result in loss are common to virtually all of the different manufacturing processes and considerable improvement in yield is possible, particularly if attention is given to careful process engineering design.

For the preparation of an intermediate‐purity concentrate the most important points are considered to be:

Provision of a good quality plasma feedstock.

Rapid processing, with no delays from initiation of plasma thawing to freezing of the final concentrate.

Continuous thawing of plasma to allow rapid thawing with precise control of temperature.

Effective centrifugation for cryoprecipitate collection.

The use of low shear agitators and careful control of pH adjustment.

In‐process control of ionised calcium concentration.

Further processing to prepare concentrates of increased purity also results in significant loss of factor VIII and new higher yielding methods are needed if high quality products are required.
Parameters Affecting the Fractionation of FVIII: C Activity in Production of Very High Purity AHF Concentrate
Authors: Törmä E , Myllylá G
Published: August 2010

A newly introduced purification method has been shown to yield in a final product of good characteristics when prime quality plasma was used in small scale. In order to assess the importance of the plasma quality in production of very high purity AHF concentrate, cryopre‐cipitates originating from various kinds of starting plasmas were fractionated according to the purification method. The parameters investigated in this study were: a) the blood group, b) age of plasma, c) storage time of plasma and d) the role of thrombin activation as monitored by FPA level. The yield of FVIII:C in the cryoprecipitate varied depending on the quality of starting plasma. In average, the relative proportion of FVIII:C which could be recovered in the final product was independent from the quality of starting plasma. The overall yields per liter of plasma were, however, decreased when starting plasma of low quality was used.
The Role of Prothrombin Complex Concentrates In the Treatment of Hemophiliacs with Factor VIII Inhibitors
Authors: Lusher J. M.
Published: August 2010

While the presence of a Factor VIII inhibitor does not increase the frequency of bleeding, it does make treatment of bleeding episodes difficult. Over the past decade prothrombin complex concentrates (PCC) have been used in an attempt to bypass the need for Factor VIII. While their precise mechanism of action is still not known, PCC do seem to be moderately effective in controlling bleeding in hemophiliacs with inhibitors. In each of three controlled double blind studies a single dose of non‐activated PCC was found to be effective in controlling acute hemarthroses in approximately 50% of episodes. While FEIBA was found to be somewhat more effective (64%) than non‐activated PCC (52%) in the Dutch trial, in the only controlled trial in which a single dose of Autoplex was compared to a single dose of non‐activated PCC there was no difference between the two products. Nonetheless a number of independent observers have noted beneficial effects when activated PCC have been used in serious, life threatening types of bleeding. Thus, until a more predictably effective therapeutic modality becomes available, PCC, both non‐activated and activated, have a definite role in the management of patients with inhibitors.
Radioactive Synovectomy in Haemophilic Haemarthrosis. Follow‐up of Fifty Cases
Authors: Fernandez‐Palazzi F , de Bosch N B , de Vargas A F
Published: August 2010

Radioactive synovectomy using gold (Au 198) and rheniun (Re 186) was performed in 50 joints of 43 haemophilic patients for recurrent haemathroses. The joints treated were 31 knees, 30 elbows, 5 ankles and 1 shoulder on five separate occasions. Three patients required injections into two separate joints and in four patients the same joint was injected twice.

In 30 joints (60 percent) no further haemarthrosis occurred over the whole follow‐up period. Bleeding was diminished in 14 joints (28 percent) but increased in 6. Overall 88 percent of joints improved with this treatment.

Prior to the synovectomy the joint was scanned with technetium (Tc 99m) to compare the inflammation before and after radioactive injection. This was repeated at six months following injection.

A leucocyte culture for chromosomal studies was performed in twelve patients after radioactive injection and in four without treatment. All lesions found (non‐specific structural changes) were of no significance and all premalignant changes noted in the first culture disappeared in further control cultures.
Review of the Transmission of Hepatitis By Clotting Factor Concentrates
Authors: Tabor E.
Published: August 2010

Hepatitis remains a serious complication of the treatment of hemophilia. Even the most sensitive assays for the hepatitis B surface antigen cannot detect every plasma unit which contains the hepatitis B virus. Some (but not all) lots of clotting factor concentrates manufactured from plasma screened for hepatitis B surface antigen have been documented to transmit hepatitis B. Chronic hepatitis B results from between 7–11 percent of hepatitis B infections in hemophiliacs; associated severe chronic liver damage has been documented in 2 percent of infections. Delta agent infection accompanying hepatitis B infection appears to be responsible for significant liver disease in some hemophiliacs.

In contrast, nearly every lot of clotting factor concentrate transmits one or more agents of non‐A, non‐B hepatitis. Chronic non‐A, non‐B hepatitis appears to result from nearly 50 percent of acute infections. Although liver damage accompanies most of these chronic cases, recent studies have suggested that partial resolution of histologic abnormalities may occur spontaneously in some hemophiliacs.
Local Hemostatic Agents (and Techniques)
Authors: Evans B E
Published: August 2010

Historically, control of bleeding in the mouth has been a challenge to oral surgeons who treat patients with acquired, idiopathic and congenital bleeding disorders. This discussion focuses on the local measures currently utilized to control bleeding in the oral cavity. It is the author's contention that the use of adjunctive local measures can make dental surgery safe for patients suffering from platelet dysfunction and from coagulation disorders, and safe as well for those patients with inhibitors to the usual corrective measures for their congenital coagulopathy. Different techniques and agents have different property characteristics, but when judiciously utilized the practitioner can derive tremendous benefit from them for the bleeding patient.
Contamination of Oral Wounds with Saliva and Bacteria
Authors: Ramström G
Published: August 2010

Surgery in the oral cavity gives very often complications in the healing process depending on contamination of all wounds with saliva and bacteria. Several reports show that pure gland saliva contains only plasminogen activator activity while mixed saliva contains both fibrinolytic and activator activity. The saliva in the oral wound thus can give increased risk for fibrinolysis of the coagulum formed. Studies of the oral bacteria as such on fibrin plates have not shown either fibrinolytic or plasminogen activator activity. However, it is well known that there are several proteases within the leukocytes capable of dissolving fibrin clots. Accordingly an infection after oral surgery caused by oral bacteria can give increased proteolytic and consequently fibrinolytic activity in the wound.

In oral surgery on patients with coagulation disorders even a small rise of fibrinolytic activity can give a postoperative bleeding. It is consequently advisable to treat these patients with antibiotics to prevent infections and to try to protect the coagulum against saliva as much as possible locally and to give fibrinolytic inhibitors such as tranexamic acid.

During many years we have treated patients with severe coagulation disorders according to these principles at factor levels as low as 5–10 per cent with a minimum of bleeding complications.
Production of Antihemophilic Factor in France
Authors: Allain J‐P
Published: August 2010

The ability of the French national blood transfusion system to provide self‐sufficiency for therapeutic coagulation factors is discussed. Adjustment to the rapidly increasing demand in both quality and quantity of Factor VIII is not toally met.

Approximately 60 per cent of the total consumption corresponds to concentrate mostly of intermediate purity and one half of this is imported. Although enough blood is collected to provide the plasma required to cover the demand, the logistic of plasma separation and the extensive use of fresh frozen plasma as plasma expander make the starting plasma for Factor VIII preparation in short supply. The development of voluntary plasmapheresis, optimization of the use of blood components, systematic collection of cryoprecipitate from each plasma unit and improvement of quality of starting plasma are necessary to achieve self‐sufficiency.
COMPARISONS OF ONE‐STAGE AND TWO‐STAGE ASSAYS OF FACTOR VIII:C
Authors: Barrowcliffe Trevor W.
Published: August 2010

ABSTRACT:  Comparisons of one‐stage and two‐stage methods are made in terms of technical aspects, precision and potency estimates. Because of the different dilution ranges and reagents, there is a higher concentration of clotting factors and total protein in the one‐stage essays, and a higher ratio of VIII R:Ag/VIII:C. The one‐stage assay is technically simpler and easier to automate, but the two‐stage method is probably more sensitive. In international collaborative studies, the two‐stage method has been generally more precise, but current differences in precision between the methods are small. Discrepancies between the methods occur in assays of concentrates against plasma standards, sometimes also against concentrate standards, and in assessment of in vivo recovery. The adsorption step used in the two‐stage method is a major cause of the discrepancy is assays of concentrates against plasma. Other possible causes of discrepancies between the methods in assays of concentrates are: pre‐dilution in buffer or haemophilic plasma; thrombin activation; the influence of VIII R:Ag on VIII:C activity; non‐specific contaminants such as lipids.
THE STATISTICAL EVALUATION OF FACTOR VIII CLOTTING ASSAYS
Authors: Curtis Anthony D.
Published: August 2010

ABSTRACT:  A brief review of the underlying principles of the comparative biological assay is given. This is followed by a more detailed discussion of the design of Factor VIII clotting activity assays and of the analysis of the data produced. Details of the calculations involved in various parts of the analysis are given in an Appendix.
QUALITY CONTROL OF THE ONE‐STAGE FACTOR VIII (VIII:C) ASSAY IN THE COAGULATION LABORATORY
Authors: Over Jan
Published: August 2010

ABSTRACT: In this chapter measures are described that should be taken to ensure the reliability and accuracy of one‐stage assays of Factor VIII coagulant activity (VIII:C). The first part deals with requirements for reagents, test conditions and procedure. The second half is dedicated to the problem of interlaboratory variation of Factor VIII assays; the results of a multicentre collaborative study on the quality control of Factor VIII concentrates are presented.
COMPARISON OF FACTOR VIII CONCENTRATES IN NON‐BLEEDING PATIENTS
Authors: Schimpf KI. , Rothmann P. , Schumacher K.
Published: August 2010

ABSTRACT: The comparison ofin vivorecovery of Factor VIII:C of 3 Factor VIII concentrates in two consecutive cross‐over studies on non‐bleeding patients suffering from a severe hemophilia A showed in both instances equally strong differences; values more than twice as high were obtained with product C than with product A. The cause for this was found to lie in the different declarations of the products. With calculations based on the results of thein vitrotesting of the concentrates, the recoveries of the 3 products largely converged. For this reason one should demand that declarations for all products be made in accordance with uniform rules.

In both studies the mean values of the half elimination times (half‐lives) of Factor VIII:C were in each case the same for the 3 products; but in study a) the mean value of half‐lives was distinctly longer (14.1 hrs) than in study b) (10.5 hrs). The recovery, too, was higher in study a) (1.96 YO) per injected unit measured than in study b) (1.4%). This occurred despite identical conditions in both studies. An explanation for this was not found.

There was a tendency towards a positive relationship between recovery and body weight.

According to the applied cross‐over design, the rank order of the Factor VIII:C recoveries found between the various concentrates were not blurred by the individual differences from patient to patient; nor were they blurred by the strong varying hematocrit values and other unknown factors relating to deviations in recovery, distribution time and elimination time from patient to patient. There can be no doubt as to the advantages of the cross‐over methodoly when performing directin vivocomparisons.
FACTOR VIII RELATED ACTIVITIES IN CONCENTRATES
Authors: Nilsson Inga Marie , Borge Lise , Gunnarsson Margoth , Kristoffersson Ann‐Charlotte
Published: August 2010

ABSTRACT: Factor VIII related activities were investigated in 3 low purity concentrates (fraction 1‐0 and freeze‐dried cryoprecipitates), 2 intermediate concentrates, and 8 high purity concentrates. The parameters studied were VIII:C by one‐stage assay and chromogenic assay, VIII clotting antigen (VIII:CAg), VIII related antigen (VIIIR:Ag) by electroimmunoassay, immunoradiometric assay (IRMA), crossed immuno‐electrophoresis (CIE) and SDS agarose gel electrophoresis followed by staining with radioactive antibody, ristocetin cofactor activity (R:RCF) and fibrinogen. The VIII:C values from the chromogenic assay method agreed well with those obtained by the one‐stage assay. The specific activity varied considerably between the different concentrates and even between different batches. DDAVP Octonativ and Factorate had the highest specific activity. With the exception of Factorate, all preparations had higher concentrations of VIII:CAg than of VIII:C — probably indicating inactivation of the biological activity of VIII:C during the manufacturing process.

Studies of the Factor VIII/von Willebrand factor showed that all the concentrates contain considerable amounts of VIIIR:Ag as measured by electroimmunoassay. The intermediate and the high purity concentrates had much lower concentration of VIIIR:Ag as determined by IRMA than by electroimmunoassay, and the dose response curves were non‐parallel. On CIE they showed an abnormal migration. Multimeric sizing demonstrated that all the intermediate and high purity concentrates were lacking in the high molecular weight multimers. Fraction 1‐0 and the cryoprecipitates, the only preparations capable of correcting the bleeding defect in patients with von Willebrand's disease, showed about the same concentration of VIIIR:Ag as determined by electroimmunoassay and IRMA, normal migration in CIE, and the same multimeric pattern as normal plasma. The VIIIR:RCF values were much lower than those for VIIIR:Ag, as determined by electroimmunoassay.

Thus, considerable differences were found of thein vitroproperties of Factor VIII related activities between low, intermediate and high purity Factor VIII concentrates. The action of proteases and the techniques used in purification probably have a crucial effect on the properties.
Application of the Beckman JE6‐B Elutriator System® in the isolation of human monocyte subpopulations
Authors: Mason Richard R. , Weiner Roy S.
Published: August 2010

Beckman Instruments recently developed an improved version of their JE‐6 Elutriator Rotorr̀. At 3000 rpm (867 x g), lymphocytes were eluted from the chamber at flow rates of 10 to 18 ml/min. Small monocytes (362 μ3) were collected at 18 ml/min over 400 ml while the larger monocytes (395 μ3) were retained in the chamber until the flow rate was increased to 28 ml/min. These parameters differ from those previously reported by us when we used Beckman's original commercial version of the JE‐6 Elutriator Rotor. The new JE‐6B rotor required an increase of centrifugal force from 625 to 867 x g generated by an increase in rpm from 2500 to 3000, as well as an increase in flow rates to collect both small (17 to 18 ml/min) and large (26 to 28 ml/min) monocytes. The monocytes collected using the new rotor with the revised protocol have the same physical and functional properties as those collected with the earlier version using our previously published protocol.
Extramedullary haemopoiesis after bone marrow transplantation
Authors: Arnold R. , Calvo W. , Heymer B. , Schmeiser T. , Heimpel H. , Kubanek B.
Published: August 2010

44 patients underwent bone marrow transplantation (BMT) for treatment of severe aplastic anaemia or haematological malignancies. During their post‐transplant phase all patients had erythroblasts and granulocytic precursors in their peripheral blood. 15 patients died between day +6 and d +346 after BMT and autopsies were performed. The sections of all 15 patients revealed extramedullary haemopoiesis in the spleen. Extra‐medullary haemopoiesis in the liver was found only in those patients who died early (between d +6 and d +21 after BMT). Medullary haemopoiesis, normally only occurring in the vertebral body, was also observed in the shaft of the femur.

The present data show that after BMT all tissues with a haemopoietic matrix in ontogenesis can be repopulated with haemopoiesis in the early phase of reconstitution, possibly to compensate for the haemopoietic insufficiency after conditioning therapy. The expansion of haemopoiesis in the later period of up to 1 year after BMT, remains to be explained.
Amelioration of hydroxyurea‐induced suppression of phagocytosis in human granulocytes by free radical scavengers
Authors: Szczepańnska Izabella , Kwiatkowska Jolanta , Przybyszewski Waldemar M. , Sitarska Ewa , Malec Janina
Published: August 2010

The exposure of human circulatory white cells in vitro to 0.1 — 1 — 10 mol/l hydroxyurea (HU) for 20 h induced a progressive dose‐dependent suppression of the phagocytic activity of granulocytes. The suppressing effect of 20 h exposure to 1 mol/1 HU was used to examine the protection afforded by free radical scavengers against HU‐induced cytotoxicity. It has been found that, in the suitable concentration of the protecting agent, a substantial protective effect of sodium benzoate, acetylosalicylic acid, α‐tocopherol, ascorbic acid, catalase, peroxidase or superoxide dismutase can be achieved.
Kinetics and in vivo distribution of 111‐In‐labelled autologous platelets in chronic hepatic disease: mechanisms of thrombocytopenia
Authors: Schmidt Kai Gjerløff , Rasmussen Jens Wæver , Bekker Claus , Madsen Poul Erik Rørbæk
Published: August 2010

The kinetics and distribution in vivo of autologous 111‐In‐labelled platelets were studied in 20 patients with chronic hepatic disease. The patients, 16 of whom were thrombocytopenic, exhibited a shortened platelet mean life time, a reduced platelet recovery and a normal platelet turnover, the latter 2 of which were positively correlated to the platelet count. Platelet in vivo recovery was negatively correlated to the spleen volume. In accordance with this, scintigraphic studies revealed that the spleen was the major organ of platelet sequestration and destruction, the role of the liver being almost negligible. Signs of platelet destruction in the bone marrow were also found. Our results indicate that splenic platelet pooling and accelerated platelet destruction, accompanied by inability of the bone marrow to compensate for the thrombocytopenia are the main causes of the thrombocytopenia accompanying chronic hepatic disease.
Distribution of HLA genotypes in sibs of patients with acute leukaemia
Authors: de Moor Pieter , Louwagie Andries
Published: August 2010

More unaffected sibs than expected have the same HLA genotypes as their sib with acute leukaemia. This seems not to be due to the restricted heterogeneity in HLA antigens described in the parents of sibs with acute leukaemia.
Transferrin receptors on circulating monocytes in hereditary haemochromatosis
Authors: Björn‐Rasmussen E. , Hageman J. , van den Dungen P. , Prowit‐Ksiazek A. , Biberfeld P.
Published: August 2010

In patients with hereditary haemochromatosis (HH) abnormal functional properties of the macrophage system have been observed. The present study is a preliminary report of increased transferrin receptor expression on monocytes from 12 patients with HH. There was no correlation between the degree of iron overload and the transferrin receptor expression on the monocytes. The results obtained thus indicate that the observed increase in transferrin receptors is not a secondary phenomenon due to systemic iron overload but could be an expression of a primary inborn error of iron metabolism in HH. The functional aspects of the receptors were not evaluated as they were analyzed by means of monoclonal antibody technique.
Lack of efficacy of high‐dose intravenous immunoglobulin in autoimmune haemolytic anaemia: a clue to its mechanism*
Authors: Mueller‐Eckhardt C. , Salama A. , Mahn I. , Kiefel V. , Neuzner J. , Graubner M.
Published: August 2010

5 patients with autoimmune haemolytic anaemia (AIHA) of warm type (4 idiopathic, 1 associated with systemic lupus erythematosus and thrombocytopenia) were treated with high doses of i.v. immunoglobulin (IgG; Sandoglobulin®; 2.0 g/kg body weight). IgG therapy was ineffective in all 5 cases as indicated by a lack of clinical improvement, continuous signs of accelerated red blood cell (RBC) destruction, and an unchanged survival rate of 51Cr‐labelled autologous RBC in 4 patients studied. IgG infused at equivalent doses into 5 healthy volunteers led to an increase of IgG coating of autologous RBC (irrespective of the ABO blood groups) without concomitant changes of haemoglobin, haematocrit or reticulocytes, increase of serum IgM in 3/5, a decrease of serum C4 in 5/5, and a decrease of serum haptoglobin in 2/5 individuals. We conclude that IgG at a dose of 2.0 g/kg body weight is ineffective in AIHA. This may be caused by an increased, though clinically inapparent, interaction of IgG‐coated autologous RBC with the mononuclear phagocyte system.
Triosephosphate isomerase deficiency: 2 new cases
Authors: Zanella A. , Mariani M. , Colombo M. B. , Borgna‐Pignatti C. , de Stefano P. , Morgese G. , Sirchia G.
Published: August 2010

2 new cases of triosephosphate isomerase (TPI) deficiency associated with severe haemolytic anaemia in 2 unrelated Italian families are described. Only 1 case was extensively investigated. TPI deficiency was detectable in erythrocytes, leucocytes, platelets and plasma. The mutant enzyme showed normal Km for GAP and increased Km for DHAP, with an higher than normal equilibrium constant, decreased thermo‐stability, and abnormal electrophoretic pattern due to the lack of the fastest moving component. The immunological characterization revealed a lower than normal inactivation by specific antiserum, while the double immunodiffusion pattern and the precipitin curve were normal. Lymphocyte, granulocyte and platelet functions were impaired.
Early T‐cell features in blast crisis of Ph1‐positive chronic myeloid leukaemia
Authors: Cervantes Francisco , Anegon Ignacio , Rozman Ciril , Gallart Teresa , Pereira Arturo , Vives‐Corrons J. L. , Casademont Jordi , Urbano‐Marquez A.
Published: August 2010

A patient with Ph1‐positive chronic myeloid leukaemia (CML) presented in extra‐medullary blast crisis. Whereas the peripheral blood and bone marrow features were consistent with the chronic phase of CML, study of the enlarged lymph nodes demonstrated massive replacement by Ph1‐positive blast cells of lymphoblastic morphology. Such blast cells showed diffuse acid phosphatase positivity, were positive for TdT, and had an enzyme pattern (adenosin‐deaminase, purine‐nucleoside‐phosphorilase and lactate‐dehydrogenase) typical of immature T‐cells. To further characterize the phenotype of the blast cells, they were analyzed for surface markers using a panel of monoclonal antibodies selected to identify differentiation antigens of T cells, B cells and myeloid cells. The results of the latter analysis were consistent with an early T‐cell origin of the blast cells, since they were positive for TdT, CRISI (T1), E rosettes and OKT10, and were negative for OKT3, Leu3 and OKT8. These features demonstrate that T‐cell markers may also be expressed in blast crisis of CML and provide evidence that T‐cells may share a common stem cell with myeloid and B‐cells in CML.
Kinetic studies on lymphocytes labelled with indium 111‐oxine in patients with chronic lymphocytic leukaemia
Authors: Matsuda Shin , Uchida Tatsumi , Kariyone Shigeo
Published: August 2010

The kinetics of 111Indium‐oxine‐labelled autologous blood lymphocytes were studied in normal subjects and 10 patients with chronic lymphocytic leukaemia (CLL). In both normal and leukaemic subjects, intravascular survival of lymphocytes was characterized by two exponential decreases, the first being a rapid one and the second slow phase. T 1/2 of the second phase for normal T lymphocytes (52.0 ± 3.2 h: mean ± SEM) was longer than that for B lymphocytes (31.6 ± 2.8 h). T 1/2 of the second phase in patients with CLL was 15.1 to 192.6 h, which correlated well with the clinical stage of CLL by the Rai classification. Body surface scanning revealed prominent splenic accumulation of labelled cells in normal individuals and patients with CLL. Lymph node visualization was recognized in all patients with T‐cell CLL; however, there was no visualization in 8 of the 9 patients with B‐cell CLL. The longer survival time and splenic and lymph node visualization suggest that an expansion of the extravascular lymphocyte pool may be important in the pathophysiology of CLL.
Lactate overproduction in platelets of subjects affected with myeloproliferative disorders
Authors: Leoncini G. , Maresca M. , Armani U. , Piana A.
Published: August 2010

In platelets of patients affected with myeloproliferative disorders, glycolytic and glycogenolytic flux have been examined. Results of studies on glucose uptake, glycogen breakdown and lactate formation have been reported. No difference in glucose uptake between controls and patients was observed, but in patients a higher lactate formation was always noted in the presence or absence of exogenous glucose, in correlation with a higher glycogen breakdown rate. Results could be explained by modified regulation mechanisms on glycogen phosphorylase.
Bone marrow response to chemotherapy in acute lymphocytic leukaemia and acute non‐lymphocytic leukaemia
Authors: Brody Judith P. , Krause John R. , Penchansky Lila
Published: August 2010

Histopathologic changes in core bone marrow biopsies were reviewed in 33 patients with acute leukaemia during chemotherapy to compare the changes in acute lymphocytic leukaemia (ALL) with acute non‐lymphocytic leukaemia (ANLL). Cellular, stromal, and bony changes were evaluated with regard to diagnosis and time of biopsy from initiation of chemotherapy. A significant difference was noted in the plasma cell response. Plasmacytosis was present in 19/19 cases of ANLL, but in only 2/14 cases of ALL. Cellular depletion was also significantly less frequent in ALL. Other stromal changes such as haemorrhage, dilatation of sinusoids and fat regeneration, as well as osteoblastic bone activity occurred with similar frequencies in all cases of treated acute leukaemia. Fibrosis, necrosis, and serous atrophy were uncommon. Differing chemotherapeutic regimens and differing patient ages were both correlated with the plasma cell response, but not with the difference in cellular depletion.
Heinz body formation in red cell membrane disorders: Its acceleration in membrane lipid abnormalities
Authors: Mannoji Masakiyo , Sugihra Takashi , Yawata Yoshihito
Published: August 2010

Abnormal Heinz body formation in the presence of acetylphenyl hydrazine was observed in some patients with red cell membrane abnormalities, such as hereditary red cell membrane high phosphatidyl choline haemolytic anaemia, congenital haemolytic anaemias of unknown origin, acquired hyperlipidaemia and paroxysmal nocturnal haemoglobinuria. No abnormality of haemoglobin composition or of oxidation‐reduction activities was noted in 66 patients studied. No abnormal Heinz body formation was seen in hereditary spherocytosis, hereditary elliptocytosis or hereditary stomatocytosis with normal membrane lipids, but increased Heinz body formation was observed in some patients with red cell membrane lipid abnormalities. The extent of abnormal Heinz body formation inversely correlated with a decreased molar ratio of free cholesterol to phosphatidyl choline in these red cells. Heinz body formation, therefore, may be abnormal in some red cell membrane disorders, especially when membrane lipid abnormalities exist.
Platelet – von Willebrand factor interactions in Type IIB von Willebrand's disease
Authors: Holmberg L. , Kristoffersson A. C. , Lamme S. , Nilsson I. M. , Awidi A. , Solum N. O.
Published: August 2010

Type IIB von Willebrand's disease (vWD) is a distinct form of this disorder in which the largest multimers of the von Willebrand factor (vWF) are lacking in plasma but present in platelets. When the vasopressin analogue, l‐deamino‐8‐D‐arginine vasopressin (DDAVP), is given to patients with type IIB vWD, an abnormal vWF is released to plasma. This vWF causes thrombocytopenia in vivo and platelet aggregation in vitro. Aggregation occurs in the plasma milieu and thus at physiological fibrinogen concentration. In this study we demonstrate that IIB post‐DDAVP vWF aggregated only metabolically active platelets. The platelet aggregation was completely inhibited by EDTA and PGE1, and either inhibited or greatly weakened by ASA, demonstrating the role of divalent cations and thromboxane A2 formation. In spite of inhibiting platelet aggregation, EDTA, PGE1 and ASA did not prevent platelet binding of IIB post‐DDAVP vWF. An antiserum against GP Ib made normal platelets less responsive to the IIB vWF although neither platelet aggregation nor vWF binding were completely prevented. The aggregation was fibrinogen‐dependent and platelets from patients with Glanzmann's thrombasthenia were unresponsive. The studies provide evidence that IIB post‐DDAVP vWF is bound to unstimulated platelets and that the interaction between vWF and platelets in type IIB vWD is different from ristocetin‐induced as well as thrombin‐ and epinephrine‐induced binding to platelets of normal vWF.
Hypercalcaemia in the accelerated phase of chronic myelogenous leukaemia: No relationship to the phenotype of the blast cells
Authors: Hasselbalch H. , Birgens H. S. , Geisler C. , Hansen N. E.
Published: August 2010

2 patients with chronic myelogenous leukaemia developed hypercalcaemia and severe myelofibrosis in the terminal phases of their disease. Hormonal studies excluded the hypercalcaemia being caused by primary hyperparathyroidism or ectopic parathyroid hormone secretion. Its development was unrelated to the phenotype of the blast cells, as assessed by conventional cytochemistry and immunological surface typing. The finding of increased urinary cAMP excretion in 1 of the patients suggests a circulating, nonparathyroid humoral bone resorbing factor with partial biological PTH‐activity to be one of the pathogenetic mechanisms responsible for the occurrence of hypercalcaemia in patients with chronic myelogenous leukaemia.
Follow‐up of normal individuals with a positive antiglobulin test
Authors: Bareford D. , Longster Q. , Gilks L. , Tovey L. A. Derrick
Published: August 2010

Over a period of 20 yr (1962–1982), 67 apparently fit donors at a Regional Blood Transfusion Service were found to have an unexplained positive direct antiglobulin test (DAT). During 1983, 26 were traced and re‐tested. 9 still had a positive DAT only 1 of whom had developed autoimmune haemolytic anaemia. 17 had become negative though in 7 of these an autoantibody could still be detected by an enzyme technique. Unlike patients with established autoimmune disorders, the positive DAT individuals were found to have normal T cell subsets though B cells were significantly increased.
Effect of sera from various vertebrate species on mouse erythroid progenitor proliferation
Authors: Butin Christophe , Blanchet Jean Paul
Published: August 2010

Sera from different vertebrate species were tested for their stimulating activity upon mouse CFU‐E growth. Crude sera were either naturally stimulating or toxic. Absorption on mouse blood and spleen cells or decomplementation removes or neutralizes the toxicity, probably mediated through natural anti‐mouse antibodies. All but 2 sera tested (ox and sheep) were stimulatory. This stimulating activity was found to be either heat‐sensitive or ‐resistant according to the sera. Upon chromatography on DEAE cellulose, 2 fractions were obtained which were both stimulatory. Whether these two stimulating activities correspond to different molecules or to only 1 absorbed on different serum proteins remains to be determined.

These results confirm previous results obtained for mouse and human sera and suggest that this cross‐reactive stimulating activity may have an important role in vertebrate erythropoiesis.
A case of Burkitt lymphoma — L3ALL with t(8;14) translocation, developed 10 years after Hodgkin's disease
Authors: Mandelli Franco , Martelli Maurizio , Cimino Giuseppe , Alimena Giuliana , Anselmo Anna Paola , De Cuia Maria Rosaria , Gastaldi Roberta , Arcese William , Papa Giuseppe
Published: August 2010

We report the case of a 38‐year‐old man, previously treated for Hodgkin's disease (HD) with chemo‐radiotherapy who, 10 years later, developed a Burkitt lymphoma (BL) as a tumour mass of the ascendent colon and regional lymph nodes and, subsequently, on leukaemic bone‐marrow cells, on the basis of histological, immuno‐logical (B phenotype, IgM‐λ) and cytogenetic, translocation t(8;14) features. The patient died a few days later; at autopsy no evidence of HD was found. This is the 2nd case of BL developing after HD so far described. The relationship between the 2 diseases is discussed and the importance of the immunodepression in the pathogene‐sis of the secondary Burkitt lymphoma is emphasized.
Human marrow stromal cells in short‐term semi‐solid bone marrow culture in aplastic anaemia
Authors: Reynolds Maura , McCann S. R.
Published: August 2010

A short‐term methylcellulose technique was used to study the proliferation of marrow‐derived stromal, erythroid and myeloid colonies from normal controls and from patients with aplastic anaemia. There was a significant reduction in all colony types in patients with aplastic anaemia when compared with normal controls. In 4 patients who achieved remission following treatment with ATG + oxymetholone or with oxymetholone alone there was a return to normal range of stromal colonies and also of CFU‐E. There was no change in the numbers of BFU‐E's and only a slight increase in the numbers of CFU‐C's.
E rosette‐positive agar colonies containing the Philadelphia chromosome in chronic myeloid leukaemia
Authors: Nogueira‐Costa Renato , Spitzer Gary , Cork Ann , Trujillo Jose M.
Published: August 2010

In an attempt to document possible T‐cell involvement in chronic myeloid leukaemia, E rosette‐positive colonies (ERPC) were grown in agar culture using a T‐cell‐conditioned medium. Colonies were grown from whole mononuclear cells (WMN), nonadherent E rosette‐positive (NAT +) and nonadherent E rosette‐negative (NAT‐) cells. Cells collected from the colonies after 10 d in culture were 99–100% E rosette‐positive. 8 metaphases were obtained from both NAT+ and NAT‐ ERPCs. In NAT‐ ERPCs, 5 out of 8 metaphases were positive for the Philadelphia (Ph1) chromosome as compared to 1 Ph1 positive out of 8 metaphases in the NAT + ERPCs. These results suggest that, at least in this particular patient we studied, a subpopulation of E rosette‐positive cells derived from the NAT‐ cell fraction express the Ph1 chromosome.
Ferrochelatase deficiency of the bone marrow in a syndrome of congenital microcytic anaemia with iron overload of the liver and hyperferraemia
Authors: Stavem Per , Romslo Inge , Hovig Torstein , Rootwelt Kjell , Emblem Ragnhild
Published: August 2010

Ferrochelatase deficiency of the bone marrow was found in 2 sisters with a syndrome of congenital hypochromic anaemia, hyperferraemia and heavy iron deposits in the liver.
Antibodies against HTLV‐III in Danish haemophiliacs: Relation to source of factor VIII used in treatment and immunological parameters
Authors: Lindhardt B. Ørskov , Gerstoft J. , Ulrich K. , Bentzen K. , Scheibel E. , Nielsen J. Dalsgård , Dickmeiss E.
Published: August 2010

18 out of 40 healthy Danish type A haemophiliacs had antibodies against HTLV‐III as measured by an enzyme linked immunosorbent assay (ELISA). The overall seropositivity was 45%. A significant positive correlation was found between seropositivity and total lifetime dose of factor VIII and the age of the patients. 63% and 79% of the patients predominantly treated with commercial American and European preparations, respectively, had antibodies, compared with 11% among patients predominantly treated with Danish cryoprecipitate. Patients exclusively treated with preparations from a single source in the year prior to investigation showed 69% seropositivity when treated with American and European preparations. None of the patients treated with Danish cryoprecipitates prepared from voluntary Danish donors had antibodies. No difference between seropositive and seronegative groups was found in total lymphocyte count, leu 2+ cells, leu 3 + cells and leu 2 +/leu 3 + ratio, but the seropositive group had significantly higher total IgG and lower skin test score. It is concluded that treatment with local European preparation carries less risk of HTLV‐III infection compared with commercial preparations from either the USA or Europe. The results also suggested that T‐cell subset alterations among haemophiliacs are not primarily due to HTLV‐III infection.
Prognostic value of the determination of serum lactic dehydrogenase and its isoenzymes in children with acute lymphoblastic leukaemia
Authors: Hi¸söUnme Gönül , Çag̈lar Kazim , Renda Nurten
Published: August 2010

Serum total lactic dehydrogenase (LDH) levels have been found to be significantly higher in 21 children with acute lymphoblastic leukaemia (ALL) at initial diagnosis than the values of 12 children who achieved remission. The mean value of serum LDH levels in patients with high‐risk factors was 2347 ± 1490 U/ml (range 430–5460 U/ml), while in patients at standard risk it was 652 ± 385 U/ml (range 110–1320 U/ml). The serum LDH values were above 1320 U/ml in 70% of the 13 children with high‐risk factors.

The serum isoenzyme patterns were analyzed in 17 of these children at the initial diagnosis. Although LDH‐3 and LDH‐2 were prominent at the time of diagnosis; LDH‐2 and LDH‐1 were the prodominant isoenzymes in remission. The highest concentrations of LDH‐3 were observed in the high‐risk group at diagnosis and the ratio of LDH‐3 to LDH‐2 exceeding 1.0 was found in children who had high‐risk factors, but not in any patients in the standard risk group.