bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormalities of chromosome 13 in myelofibrosis
Authors: Borgström G. H. , Knuutila S. , Ruutu T. , Pakkala A. , Lahtinen R. , de la Chapelle A.
Published: August 2010

19 patients with myelofibrosis, primary or following polycythaemia vera were studied cytogenetically. Bone marrow cells, unstimulated and stimulated cells from peripheral blood were investigated. 7 patients were found to have clonal aberrations, 3 of whom had a structural rearrangement of chromosome 13. In 2 additional cases single mitoses with 13q‐ were found. Reviewing the files on patients previously studied in our laboratory, 2 more patients with 13q‐ markers were noted. Both had had haematologic disorders in which fibrosis of the bone marrow can be found, but this feature could not be evaluated retrospectively, because no biopsies had been taken. Our data and those found in the literature suggest that rearrangements of 13q12 → q22 are often associated with myelofibrosis, both in its primary form or following polycythaemia vera.
Cytogenetic findings in acute promyelocytic leukaemia A report of 25 cases
Authors: Alimena G. , Dallapiccola B. , De Cuia M. R. , Gallo E. , Gastaldi R. , Nanni M. , Franchi A. , Mandelli F.
Published: August 2010

Cytogenetic analyses of bone marrow cells were carried out by means of direct technique and short‐term cultures in 25 acute promyelocytic leukaemia (APL) patients. 16 were affected by the hypergranular form and 9 by the M3‐variant. The t(15;17) was documented at diagnosis in 15 patients. In addition, 2 cases, in which an M3 morphology and a normal karyotype on direct preparation were found at diagnosis, disclosed the chromosome anomaly in cultured cells at relapse, in concomitance with a change of blast morphology to the M3‐variant. However, the t(15;17) was a consistent feature in 5 of the 15 patients with cells analysed on direct preparations only and in all cases who had successful bone marrow cultures. Overall, the 15;17 translocation was detected in 7 out of 9 patients with the M3‐variant and in 8 out of 16 patients with typical M3. Whenever the chromosome preparations were made after culture, 7/7 had the translocation in the M3‐V group and 5/5 in the M3 group. No obvious differences in clinical features or outcome were evident in the patients, irrespective of their cytogenetic findings.
IN MEMORY OF ERIK JORPES
Authors: Nilsson I M
Published: August 2010

I should like to present this review in memory of the late Professor Erik Jorpes. Born on Kökar in the Åland archipelago, Erik Jorpes was our mentor when we began working on von Willebrand's disease; and his interest, his support and enthusiasm, were a splendid encouragement to us.
Hemophilic Arthropathy — An Immunologic Study of the Synovium
Authors: Andes W.A. , Walker P.D. , Edmunds J.O. , Wulff K.M.
Published: August 2010

Joint tissue from 7 patients with severe Factor VIII deficiency was examined for immune deposits. Tissue was obtained from fresh surgical specimens and offered information from patients treated by a variety of methods. No immune deposits were located, and in spite of others' suggestions that immune phenomena are occurring in the plasma of patients with hemophilia, no evidence for immune damage appeared in the joint tissues from these patients with hemophilic arthropathy.
Surgical Synovectomy for Haemophilic Arthropathy of the Knee Joint Long‐term Follow‐up
Authors: Matsuda Y. , Duthie R.B.
Published: August 2010

The results of surgical synovectomy for haemophilic arthropathy of 9 knees in 8 haemophiliacs were evaluated. Finally intra‐articular bleeding ceased in 3, reduced in 2 and was unchanged in 3 knees. Synovectomy can be regarded as an effective procedure for haemophilic arthropathy in terms of haemostasis. Preoperative radiographs in unsuccessful cases showed more advanced changes of arthropathy and the age at operation was all over 20 years old. Five knees reduced in joint mobility after the operation. There was less progression of radiological arthropathic changes in the knees where intra‐articular bleeding ceased or reduced postoperatively, whereas no knees showed radiological improvement of arthropathy. Synovectomy should be viewed as a haemostatic procedure and be performed on those under 20 years of age with radiologically less advanced arthropathy joint, when sufficient conservative treatment has failed to eliminate repeated haemarthroses.
Arthroscopic Synovectomy in the Treatment of Hemophilic Synovitis
Authors: Kim H.C. , Klein K. , Hirsch S. , Seibold J.R. , Eisele J. , Saidi P.
Published: August 2010

Chronic proliferative synovitis is a frequent complication of hemophilia for which effective treatments are lacking. Over a three year period we employed arthroscopic surgery on 7 knees in 6 patients with hemophilic synovitis refractory to standard treatment including anti‐inflammatory drugs, prophylactic factor infusion and physical therapy. Operative findings included diffuse villous synovial proliferation covering most cartilagenous surfaces of joint spaces in all six cases, varying degrees of articular erosion, osteochondral defects, and various forms of meniscal tear. One patient with an advanced degree of arthropathy had an extensive scar and interarticular fibrous band adhesions. Peri‐operatively morbidity was minimal, permitting early institution of physical therapy. Joint effusion resolved within one month of surgery. During the 6 month to 3 year post‐operative follow‐up, bleeding frequency was markedly reduced in all cases. In contradistinction to open surgical synovectomy, which encountered an unacceptably high incidence of post‐operative reduction in joint mobility, the range of knee joint motion after arthroscopic synovectomy was well preserved or improved in 4 of 6 patients. Two patients have lost the range of knee joint motion in post‐arthroscopic follow‐up; one patient sustained a tibial fracture requiring a long leg cast on the same knee, and the other had severe arthropathy with a reduced range of motion prior to arthroscopy. All patients have experienced pain relief and improved knee function. We conclude that arthroscopic synovectomy is a promising treatment of chronic hemophilic synovitis of the knee with low surgical morbidity and with long‐term benefit comparable to or better than that reported with open synovectomy.
Removal of Hepatitis Virus Infectivity from Clotting Factor Concentrates
Authors: Gerety R.
Published: August 2010

Viral hepatitis remains a serious problem following intravenous therapy with plasma derivatives such as clotting factor concentrates. The risk of hepatitis B has been reduced but not eliminated by screening plasma for hepatitis B surface antigen (HBsAg) by sensitive tests prior to its use in manufacturing plasma derivatives. The use of hepatitis B vaccine has the potential to eliminate completely the risk of hepatitis B transmission among hemophiliacs when administered prior to the initiation of clotting factor concentrate therapy. Non‐A, non‐B hepatitis remains a significant risk for hemophiliacs. Neither a screening test to detect transmitters of this disease nor a vaccine to prevent it appear likely to be developed in the near future.

Methods to remove, immunologically neutralize, or inactivate viruses in clotting factor concentrates have been studied. Three methods to remove hepatitis B virus from clotting factor concentrates have been evaluated. Solid‐phase immunoadsorption, polyethylene glycol precipitation and hydrophobic interaction chromatography can each remove HBsAg and hepatitis B virus (HBV) from plasma and/or clotting factor concentrates but none appear adequate to assure consistent removal of all infectious HBV. Immunological neutralization of HBV in clotting factor concentrates by the addition of neutralizing antibodies (anti‐HBs) has been accomplished. This method is applied routinely in one country to all plasma derivatives with the potential to contain infectious HBV. Immunological neutralization can only be accomplished, however, for hepatitis B virus since neutralizing antibodies for non‐A, non‐B hepatitis virus(es) have not yet been identified. The differential stabilization of plasma clotting factors to heat by a variety of specific methods has permitted the heating of clotting factor concentrates to inactivate hepatitis viruses while retaining acceptable biological activity of the clotting factors. Available data indicate that heat inactivation of both HBV and non‐A, non‐B hepatitis agents in clotting factor concentrates can be accomplished.
Immunization of Haemophiliacs Against Hepatitis B
Authors: Hedner U. , Hansson B.G. , Vermylen J. , Verstraete M. , Colaert J. , Desmyter J.
Published: August 2010

Patients with bleeding disorders (N = 30) subjected to a current risk of contracting hepatitis B by treatment with plasma products as well as normal individuals (N = 75) were immunized with MSD's hepatitis B vaccine. Eight haemophiliacs were immunized in Leuven, Belgium, and 22 in Malmö, Sweden. 53 of the controls were immunized in Leuven (26 s.c. and 27 i.m.) and 22 in Malmö. The immunogenicity was the same in haemophiliacs as in the controls showing a more potent reaction in individuals <10 years of age. No difference was found between individuals s.c. immunized and those given the vaccine i.m. In the Malmö material 2 of 22 controls did not respond to the immunization after 9 months. Both these individuals were female, >10 years old and belonged to the control group. Very few adverse reactions (swollen, sore arm) were observed.
Antigen‐Antibody Complexes in Hemophilia
Authors: Hilgartner M
Published: August 2010

Antigen‐antibody complexes have been found by several groups of investigators in patients with hemophilia. The amount of circulating immune complexes (CIC) has varied with the assay method, the largest amount has been found with the Staph binding assay and the smallest with the Raji cell method. We have correlated the level of immune complexes detected by both the Raji cell and the Staph binding assay with clinical disease status: joint disease, positive inhibitor status, and hematuria but not hepatitis. The complexes are formed with different antigens, Factor VIII, the Factor VIII inhibitor, and antibody to the hepatitis B surface antigen for example have been detected in isolated CIC. CIC have not been detected in synovium or vasculature and rarely in the synovial fluid. The effect of the infusion of concentrate on the levels of the immune complexes is variable among patients but consistent within individuals over time. Studies by our group show a rise in CIC in 3 patients and a fall in six following concentrate infusion with return to baseline in 24 hours. In vitro studies of the monomuclear phagocyte system Fc receptor function showed enhanced function in those six patients whose levels decreased post infusion while the three with rise in CIC showed a prolonged clearance and decreased mononuclear phagocyte system function. This effect was not correlated with the amount of infusion or the yearly use of the concentrate. Changes in CIC were not due to infusion of preformed complexes in the Factor VIII concentrate nor to de novo formation of CIC since in vitro incubation of pre‐infusion serum with concentrate revealed no change in CIC levels. However, change in reticulo endothelial Fc receptor function correlated with the changes in CIC suggesting a modulation of monocyte function by Factor VIII concentrate infusion. In summary, circulating immune complexes are present in transfused hemophiliacs which may be associated with secondary disease, and regulation of the immune function in these patients.
Haemophilia in Children. Current Immunologic Status of a Pediatric Population
Authors: Carnelli V , Giulotto P , Magnolfi C , Cordini M , Simoni L , Cultrera S , Bardare M
Published: August 2010

Immunological parameters were studied on two occasions in 33 children with severe hemophilia. In the second study ‐ one year after the first 80% had a decreased and 8 (31%) an inverted OKT4/OKT8 ratio, due to an increased number of T‐suppressor cells. These changes were correlated to the dose of factor concentrate given during the last year. In a third study the short time influence of a factor concentrate infusion on different immunological assays was not found to be significant. When evaluating immunological parameters in hemophiliacs it is necessary to consider other significant factors that might influence the immune system such as chronic hepatits and intercurrent infections.
Alteration of T Lymphocyte subpopulations in Swedish Hemophiliacs
Authors: Biberfeld G , Blombäck M , Egberg N , Lenkei R , Nilsson I M , Porwit‐Ksiazek A
Published: August 2010

T cell subpopulations were determined in 88 Swedish patients with severe hemostatic disorders treated with domestic or imported American factor VIII or Swedish factor IX preparations at two centres, Karolinska hospital (KH) and Malmö hospital (MH). Among the patients with severe hemophilia A from KH, all of whom had received American factor VIII concentrate, a decreased T helper/T suppressor (Leu 3/Leu 2) cell ratio (below 0.8) was found more frequently in adults (8 of 10) than in children (1 of 10). In the study of patients from MH, 15 of 18 adults and 4 of 8 children with severe hemophilia A, who had been treated with American factor VIII concentrate, had a decreased Leu 3/Leu 2 cell ratio. Decreased T cell ratios occurred also in hemophiliacs treated only with concentrates of Swedish origin. Thus 3 of 5 adults and 1 of 10 children with severe hemophilia A treated with Swedish factor VIII preparations (usually fraction 1‐0) as well as 2 of 8 adult hemophilia B cases treated with Swedish factor IX concentrate had a ratio below 0.8. There was no relationship between the T cell ratio and the amount of factor VIII of American or Swedish origin (expressed in units per kg and year) received during the previous two years.
Von Willebrand's Disease: State of the Art
Authors: Bowie E J W
Published: August 2010

Von Willebrand's disease is a familial bleeding disorder affecting both sexes and is due to the absence, decrease or abnormality of a plasma protein — the von Willebrand factor. This white paper on the disease was prepared by an international committee of the World Federation of Hemophilia. The clinical features of the disease are discussed and the nomenclature of the factor VIII complex is presented. The variant forms of the disease are classified and there is a detailed discussion of the problems in diagnosis. Finally, an approach to treatment is outlined including use of cryoprecipitate and DDAVP.
Application of an Educational Program for Patient and Family in Japan
Authors: Inagaki M , Yamada K
Published: August 2010

To obtain the best results from comprehensive care and home infusion treatment of hemophilia education of patients and family members is very important. In our comprehensive hemophilia center where more than 250 hemophiliacs are treated, such an educational program is being carried out. We are using a modification of the program of the National Hemophilia Foundation of the United States and of the World Federation of Hemophilia. Our module consists of 133 items with explanations in nine parts, i.e. basic information, family guidance, factor replacement therapy, home infusion therapy, side effects, genetic education, as well as orthopedic, dental and psycho‐sociological care. A doctor or a nurse acting as coordinator arranges a pre‐test followed by specific instructions. A follow‐up test is carried out to confirm that the test is correctly understood. At present 85 of 125 patients receiving home infusion therapy as well as 123 family members, have finished their educational program. The test results were very good: 60 to 80 percent of the answers in each part of the pre‐test were correct and, in the post test an 85 to 95 percent score was recorded. Overprotection by or confusion of the mother tended generally to lower the results of the family. This educational program seems to be an excellent way, not only to help the hemophiliac and his family to cope with his disease, but also to inform the recently diagnosed patient about his disease.
The Development and Use of an Illustrated Hemophilia Guide to Assist the Nurse in her Role as an Educator
Authors: Beha L , Belanger G , Brackmann Ch , Fearns M , Holbrock T , Meredith K
Published: August 2010

The mode of haemophilia care has changed in many instances from the hospital to the home environment. As a result of this the nurse's role has altered. More of her time is spent on education and therefore a basic guide was developed to assist. This guide has been developed by Task Force I Nursing Subcommittee for those interested in hemophilia care, more specifically the haemophiliac and his family. It is intended to give basic information about the most relevant aspects of haemophilia and the treatment of the disorder. Most of the information is given pictorially for use in countries where visual aids are more relevant than the written word. The format of the guide is set out in three sections, each page removable.

Primary information

Bleeding in hemophilia

Treatment and management
The Development of Blood Coagulation Laboratory Facilities in China and Their Use in Hemophilia
Authors: Zhen‐yi Wang , Zhu Chen , Shao Hui‐zhen , Hong‐li Wang
Published: August 2010

In China, at least 9 medical centers are carrying out the studies on factor VIII, especially on hemophilia A.

A rabbit antiserum to human VIIIR:Ag was prepared in 1980 and 661 cases were studied with the antiserum, comprising 213 cases of hemorrhagic diseases and 448 cases of normal pregnant women and non‐hemorrhagic diseases. The results were similar to those reported in medical literatures. VIIIR:Ag increased progressively with the evolution of the pregnancy reaching up to 230 percent at the third trimester, very close to that observed in toxemia of pregnancy, while the blood from umbilical cord had a normal level of VIIIR:Ag.

Studies on the localization of VIIIR:Ag with the antiserum and staphylococcus protein A linked with horse‐raddish peroxidase introduced by our laboratory confirmed its localization in endothelium cells, similar to the results obtained by classic indirect immunofluorescent staining.

Three medical centers have been studying the carriers of hemophilia A. The results are shown in Table 3. It appeared that VIIIC/VIIIR:Ag was the most sensitive and simplest parameter for discriminating hemophilia A carriers.

VIII:C/IX:C did not elevate the sensitivity of the discrimination.
To What Extent Can Plasma Supply for Factor VIII Production, Be Obtained Within the Frame of a Blood Component Program?
Authors: Högman C. F.
Published: August 2010

A country's total need of plasma for the production of Factor VIII preparations can be covered completely within an efficient blood component program, but only under certain conditions.

If the need of Factor VIII is 2 IU per inhabitant and the final yield of Factor VIII:C in the preparation is 30% of original, fresh plasma from 50% of the blood units is sufficient at an annual blood collection rate of 50,000 per million inhabitants. These figures are realistic in a cryoprecipitate program and allow sufficient plasma for substitution of plasma protein loss in other medical care than hemophilia.

In a program with predominantly high‐purity Factor VIII concentrates, additional plasma must be obtained by plasmapheresis or overcollection due to the present lower final yields in these products.
Factor VIII Production and Usage in Hungary
Authors: Elödi S. , Hollán S.R.
Published: August 2010

Factor VIII is supplied by the Hungarian Blood Transfusion Service mainly in the form of small‐pool cryoprecipitate. Blood for cryoprecipitate production is collected from non‐remunerated donors. About 600,000 voluntary donors, i.e. 6 percent of the population are giving blood yearly. Cryoprecipitate is produced by 39 blood centers distributed evenly within the country. In 1982 6.6times106 units of F.VIII was produced. There are 462 haemophilia A and 164 von Willebrand's patients in Hungary. 50 percent of the patients is under care in the National Institute and an appropriate percent of the national factor VIII production is also used here. 36 percent of our A patients belong to the severe form of the disease and are the main users of factor VIII. About 10% of the patients with von Willebrand's disease also need frequent factor replacement. The factor VIII supply of the regular users is estimated to be about 20,000 U/case/year.
Plasma Resource Planning in Canada
Authors: Grove G. , Strawczynski H. , Derrick J.B.
Published: August 2010

Since 1977 there has been an organized cooperative venture in Canada with regard to Hemophilia Care. Involved have been the Canadian Hemophilia Society, Canadian Red Cross and Government. Our paper outlines the development of the regional centers in the country and the process for data accumulation. Data is provided outlining the types and amount of Factor VIII provision developed in the country and the method of distribution.

Various undertakings have been initiated by the cooperating groups including the investigation of quality of product problems, educational symposia and the development of a long term program toward national self sufficiency.
The Changing Organization (or Roles) of the World Federation of Hemophilia
Authors: George R E
Published: August 2010

This paper discusses the changing roles of the World Federation of Hemophilia (W.F.H.).

Since its inception, the W.F.H. has played a major leadership role in providing a forum for the exchange of scientific and medical information. Credit needs to be given to this forum for advances in medical treatment. However, it has been shown that effective comprehensive care for the hemophiliac requires the participation of not only the health care team, but also the support of lay members and agencies in the community which include the W.F.H. and National Societies.

This was recognized in the formation of Task Forces by the W.F.H. Task Forces I and II represent the delivery of care, and the manufacture and use of concentrates. They can be considered as of most concern to the medical professionals. Task Force III represents the concerns of the hemophiliac and those supporting hemophiliacs.

Task Force III represents a new emphasis for the W.F.H. in congresses and organization.

This change could be labelled as, “A strategy to move towards a parity between lay and medical groups within the W.F.H.”

One can view the medical programs of the W.F.H. including congresses, I.H.T.C. (Int. Hemophilia Training Centers), regional seminars and sessions, etc., as having parallel programs for the lay members. Administrative manuals, poster descriptions, maps, the Guide for the Travelling Hemophiliac for training, information systems, etc., are examples of programs which illustrate the importance of this new role for the W.F.H.

Special programs need to be designed for the “isolated” hemophiliac. An isolated hemophiliac has been defined as one who is not getting appropriate care for any of the reasons of location, economics, health care, etc., and is at risk. Such a person could also be defined as “disadvantaged”.
AIDS and the Executive Director Perspectives in Crisis Management
Authors: Brownstein A P
Published: August 2010

Acquired Immune Deficiency Syndrome (AIDS) repreents a new risk to those with hemophilia. Initially, cases were reported among hemophiliacs in the United States, but now a number of cases have also been reported among hemophiliacs in other parts of the world. As a medical and human problem, the ramifications of AIDS are quite broad. It is important that hemophilia societies anticipate the management implications associated with this new phenomenon. The management dimensions include: information management; policy management; fiscal management; fund raising; and planning for the future.

Information and policy management are addressed in detail, and the following major points are made:

effective information management requires complete and accurate information, as well as a tight control over the flow of information;

it is important that the problem is defined in relations with the media;

policy management needs to be structured in a way that allows for ready flow of decisions related to day‐to‐day operations, while assuring full accountability and broad medical involvement in establishing overall policy direction;

methods need to be developed for implementing policy and

it is important to maintain ongoing programs other than AIDS, even if at a reduced level.
PRINCIPLES OF IN VIVO RECOVERY AND SURVIVAL STUDIES
Authors: Allain Jean‐Pierre
Published: August 2010

ABSTRACT:  The great variety of Factor VIII preparations available to the clinician to treat hemophilia A patients requires a careful study of both in vivo recovery and survival of VIII:C. These studies are valid only if strict rules are followed. Severe hemophilia A patients without inhibitor, non bleeding or bleeding in small capacity joints and not treated for at least five days are selected. The dose of infused VIII:C can be calculated either from the labeled value or from local measurement using a concentrate calibrated against the WHO standard as reference. At least 20 IU/kg of body weight of VIII:C are infused. Plasma samples collected before, 15, 30 and 60 minutes post‐infusion allow to identify the peak of VIII:C plasma level from which in vivo recovery is calculated. Samples collected 4, 8–12, 24 and 36–48 h post‐infusion allow to evaluate VIII:C half‐life on the basis of VIII:C plasma level of 4 of these samples. Both one‐ and two‐stage Factor VIII assay are equally acceptable provided a proper reference calibrated against the WHO plasma standard is used. In vivo recovery is expressed in percent of a theoretical value obtained by various means. Several mathematical formulae are available to calculate the VIII:C biological half‐life. These in vivo studies are not only useful to evaluate therapeutic preparations but also to detect low titer inhibitors.
Kinetics and distribution in vivo of 111In‐labelled autologous platelets in idiopathic thrombocytopenic purpura
Authors: Schmidt Kai Gjerløff , Rasmussen Jens Wæver
Published: August 2010

The kinetics of autologous 111In‐labelled platelets were studied in 26 patients with ITP. The platelet mean life time (MLT) was considerably shortened, the platelet in vivo recovery slightly lowered and the platelet turnover normal. Comparative studies of the kinetics of simultaneously injected 111In‐ and 51Cr‐labelled platelets in 10 patients showed the MLT and turnover of 51Cr‐platelets to be shorter and higher, respectively, than those of 111In‐platelets, suggesting that 51Cr‐labelling in ITP may underestimate platelet MLT and overestimate platelet turnover. Our results confirm that accelerated platelet destruction is an important pathogenetic factor in ITP, and that the platelet concentration may be influenced by increased splenic platelet pooling and by inability of the bone marrow to respond adequately to the low platelet count. Our scintigraphic studies showed that the spleen played an important role for platelet destruction in most patients, with the liver contributing in some patients.
Intermediate and high‐dose ARA‐C and m‐AMSA (or daunorubicin) as remission and consolidation treatment for patients with relapsed acute leukaemia and lymphoblastic non‐Hodgkin lymphoma
Authors: Willemze R. , Peters W. G. , van Hennik M. B. , Fibbe W. E. , Kootte A. M. M. , van Berkel M. , Lie R. , Rodenburg C. J. , Veltkamp J. J.
Published: August 2010

27 patients (aged 15–55 years) with relapsed acute myelogenous (AML) and lymphoblastic leukaemia (ALL), and with lymphoblastic non Hodgkin's lymphoma (NHL) have been treated with intermediate dose cytosine arabinoside (AraC, 1 g/m2q 12h x 12) and 3 d of m‐AMSA (20 patients), 90–115 mg/m2daily, or daunorubicin (7 patients). 18 of them attained a complete remission (AML 10/14, ALL 3/5, NHL 5/8). 7 patients received consolidation treatment with 1–2 courses comprising 4 d of AraC (3 g/m2q 12 h x 8) and m‐AMSA (90–115 mg/m2) on d 5 of each course. 2 patients underwent allogeneic bone marrow transplantation and 9 received no further treatment after remission induction.

In addition to vomiting, fever and conjunctivitis, toxicity in 6 patients included a combination of severe diarrhoea, fever and signs of paralytic ileus. 3 of them died during the pancytopenic phase. The pancytopenic period ranged from 16–25 d (median 21 d) after the remission induction and 14–21 d (median 19 d) after the consolidation course. Median remission duration was 5 months for those patients who received no treatment after remission induction and >9 months (4+‐16+ months) for the patients who received consolidation courses. Increased dosages of AraC are active in relapsed leukaemia and lymphoma, although optimal dose and schedule are still undetermined.
Lactoferrin in plasma measured by an ELISA technique: Evidence that plasma lactoferrin is an indicator of neutrophil turnover and bone marrow activity in acute leukaemia
Authors: Birgens Henrik S.
Published: August 2010

This study describes an ELISA technique with high specificity, sensitivity, accuracy and reproducibility for measurements of plasma lactoferrin. The detection limit was 0.001 μg/ml and the median value obtained in EDTA plasma from 47 healthy adults was 0.100 μg/ml (0.05 fractile: 0.046 μg/ml, 0.95 fractile: 0.257 μg/ml). The lactoferrin concentration in serum was on the average 2½ times higher than in plasma. The ambient temperature did not influence the plasma concentration during the first 6 h from blood sampling to separation of plasma from the cells.

In 8 patients with untreated acute leukaemia plasma lactoferrin was positively correlated to the peripheral neutrophil count. An almost parallel course in plasma lactoferrin and peripheral neutrophil number was observed in 4 patients with AML during chemotherapy. In 2 patients achieving complete remission, plasma lactoferrin increased about 6 d before the concomitant increase in neutrophil count, suggesting plasma lactoferrin as an early predictor of bone marrow regeneration.
Splenic pulp, plasma cells and foamy histiocytes in immune thrombocytopenia: Combined morphometric immunohistochemical and ultrastructural studies
Authors: Kristensen Jørgen , Jensen Olaf Myhre
Published: August 2010

Spleens from 16 splenectomized patients with immune thrombocytopenia (ITP) were compared with 10 controls (accidental and incidental splenectomy, staging laparotomy). Fresh unfixed material was secured for smears and cryostat sections, and splenic tissue was fixed by perfusion for histomorphometric, immunohistochemical and ultrastructural examination. The volumes of white pulp, including germinal centres, red pulp, and trabeculae and vessels were estimated. The ratio plasma cells containing various Ig‐classes/total nucleated cells and the ratio immature/mature plasma cells were determined and the occurrence and character of foamy cells examined.

There were slightly increased absolute volumes of white pulp, red pulp and trabeculae + major vessels in ITP, but the differences were not statistically significant. There was a statistically significant raised number of IgG‐, IgA‐ and IgM‐containing plasma cells in the germinal centres in ITP. More IgG‐containing cells seemed to be immature than in controls, but the difference was not statistically significant. Light microscopy showed foamy histiocytes in 7 of 16 cases, but electron microscopy showed them in all cases of ITP. Foamy histiocytes reacted with antithrombocyte serum.
Successes and failures of intravenous immunoglobulin
Authors: Atrah Hasan I. , Crawford Robert J. , Gabra Gamal S. , Mitchell Ruthven
Published: August 2010

11 patients suffering from primary and secondary severe haematological disorders of possible immune origin were treated with high‐dose intravenous immunoglobulin. The responses obtained were partial in 3 and negligible in 8.
Plasma cyclic nucleotide levels in patients with homozygous beta‐thalassaemia
Authors: Peracchi M. , Toschi V. , Lombardi L. , Bamonti‐Catena F. , Maiolo A. T. , Bareggi B. , Massaro P. , Polli E. E.
Published: August 2010

To investigate the possibility that a proliferative non‐neoplastic process influences extracellular cyclic nucleotide concentrations, we measured plasma cyclic AMP and cyclic GMP levels in 38 patients with homozygous beta‐thalassaemia. This group consisted of 20 patients with thalassaemia major transfused regularly (mean pre transfusion Hb levels, 11 g/dl), and 18 patients with thalassaemia intermedia who did not require regular blood transfusion (mean Hb levels, 8.7 g/dl). In the patient group, plasma cyclic AMP levels were similar to those of 37 normal subjects matched for age and sex, whereas plasma cyclic GMP levels were markedly higher. Moreover, in the thalassaemic patients there was a significant negative correlation between plasma cyclic GMP levels and haemoglobin concentrations, suggesting that their marked erythroid hyperplasia may play a role in determining alterations in extracellular cyclic GMP levels.
Long‐term high dose factor VIII treatment of 3 haemophiliacs with factor VIII inhibitor
Authors: Scheibel E. , Feddersen C. , Hertz H.
Published: August 2010

3 patients with haemophilia A and inhibitor against Factor VIII were developing progressive haemophiliac arthropathy due to the non‐feasibility of prophylactic treatment. In order to suppress inhibitor formation, long‐term treatment with high‐dose Factor VIII (100 units per kg body weight twice daily) was initiated. Prothrombin complex concentate was given only for bleeding episodes. Though all 3 patients were high responders, they presented different treatment courses. 2 became low responders after 4 and 11 months' treatment, respectively. 1 patient had no demonstrable inhibitor after start of treatment. In all 3 patients, prophylactic treatment was established, in 1 case still with increased doses compared to non‐inhibitor patients. The high‐dose Factor VIII treatment makes in possible to provide prophylactic treatment for the high‐responder inhibitor patients. However, the extremely high costs represent a serious obstacle to this treatment.
Sézary syndrome: phenotypic and functional characterization of the neoplastic cells
Authors: Ralfkiaer Elisabeth , Wantzin Gunhild Lange , Larsen Joergen K. , Andersen Vagn , Geisler Christian , Plesner Torben , Thomsen Kristian
Published: August 2010

Phenotypic properties of the neoplastic cells in skin, blood and lymph node specimens from 5 patients with the Sézary syndrome were examined by immuno‐enzymatic and ‐fluorescence labelling of cells and tissue sections with a monoclonal antibody panel. In 3 cases, the in vitro functional properties of the neoplastic cells (isolated from blood specimens) were also analysed using a reverse plaque‐forming cell assay. 3 different immunological categories were identified as follows: (1) T‐helper/inducer neoplasms (3 patients); (2) T‐suppressor/cytotoxic neoplasms (1 patient); and (3) neoplastic T‐cells demonstrating characteristics consistent with a concept of their derivation from inducible suppressor T‐cells (1 patient). These data provide conclusive evidence that Sézary syndrome is heterogeneous with respect to the immunological characteristics of the neoplastic cells.
Quantitative evaluation of monocyte differentiation by electron microscopy: Impairment of differentiation ability in monocytes from children with acute lymphoblastic leukaemia
Authors: Tsukada Masashige , Hara Yoji , Sugiyama Hiroshi , Yoda Satoru , Hara Toshihiro , Komiyama Atsushi , Akabane Taro
Published: August 2010

The differentiation of monocytes was evaluated quantitatively by electron microscopy and was analyzed in relation to the clinical features of childhood acute lymphoblastic leukaemia (ALL). The monocyte cellular size increased and cell organellae became mature after a 72‐h culture. Phagolysosome formation developed markedly‐ and the nucleus became circular‐ accompanied by chromatin deconcentration. The differentiation degree of the cell organellae was indexed and classified as mature by electron microscopy. The indexes of nuclear shape, chromatin deconcentration, cytoplasmonuclear ratio and vacuole formation increaed with time. The total index increased linearly with time dependence. These results indicate that the ultrastructural parameters and indexes allow a quantitative assessment of cell organellae and cellular differentiation of the monocyte. At the acute phase of ALL, the degrees of cell organnellae and cellular differentiation were significantly lower than the control. The above findings suggest that monocytes from children with ALL have impaired differentiation ability, which results in defective function of macrophages.
3H‐thymidine uptake in B cell lymphomas — Relationship to treatment response and survival
Authors: Kvaløy Stein , Marton Per F. , Kaalhus Olav , Høie Johan , Foss‐Abrahamsen Arne , Godal Tore
Published: August 2010

Cell suspensions were obtained from biopsy tissue from 149 patients with B cell lymphomas and analysed with regard to DNA‐synthesis as assessed by3H‐thymidine uptake, response to therapy and survival. The3H‐thymidine uptake was significantly increased in lymphomas of high versus low grade malignancy (p = 0.0001), in patients with stage I and II versus stage III and IV (p = 0.014), and in patients with general symptoms (p = 0.0025) as opposed to asymptomatic cases. The complete response rate was significantly higher in patients with increased thymidine uptake than in those with low uptake, 26/51 (51%) cases versus 24/83 (29%) cases, respectively (p = 0.014). 55 patients with increased3H‐thymidine uptake survived for significantly shorter times than (94 patients) with low uptake (p = 0.0056). Furthermore, a markedly larger group of high‐risk patients was identified by the3H‐thymidine assay than by histopathology alone, 55 cases versus 23 cases, respectively. Among the patients (126 cases) with low grade tumours, those with increased3H‐thymidine uptake (40 cases) had poorer outcome than those with low uptake (86 cases) (p = 0.045). The data suggest that DNA‐synthesis in this study, as assessed by3H‐thymidine uptake, is an independent indicator of survival in NHL. Furthermore, it may be a useful parameter in laying down guidelines for therapy in B cell neoplasms, especially in low grade tumours.
Progressive multifocal leucoencephalopathy in Hodgkin's disease
Authors: Bjerrum Ole Weis , Hansen Ole Evald
Published: August 2010

A case of progressive multifocal leucoencephalopathy in a 43‐year‐old man with Hodgkin's disease is presented. 17 similar cases from the literature are reviewed. Clinical implications of sex‐ratio, age‐distribution, diagnostic procedures and clinical course are discussed. Special attention is paid to the distribution of cases correlated to the lapse of time between diagnosis of Hodgkin's disease and symptoms of progressive multifocal leucoencephalopathy, indicating progressive multifocal leucoencephalopathy to be either a dormant infection, activated by Hodgkin's disease, or a haphazard complication. Both possibilities could be due to an impaired cell‐mediated immune response.
Classification and prognostic variables in myelomatosis
Authors: Hansen Ole Paaske , Galton David A. G.
Published: August 2010

It is difficult to compare the results of treatment obtained in different trials in myelomatosis because different sets of diagnostic criteria are used, and because the criteria by which patients are deemed eligible for entry vary. Thus the composition of different series of patients varies considerably. Furthermore, the outcome of treatment is recorded in different ways. Uniformity in the diagnostic categories entered would reduce the variance in survival between different trials: for example, trials in myelomatosis should exclude patients with monoclonal gammopathy of uncertain significance, non‐progressive or indolent myeloma, extramedullary plasmacytoma, and plasma‐cell leukaemia. The subdivision into simple prognostic groupings such as those proposed by the Medical Research Council is helpful in interpreting the survival patterns in different trials in which the proportions of patients in different prognostic groups are likely to vary. These groupings and other staging systems do not correlate with responsiveness to treatment. Rapid responders fare worse than slow responders, and this might provide a basis for a second randomisation to test whether a change in treatment could benefit the rapid responders.
Acute lymphocytic leukaemia with t(4;11): A clinical subentity
Authors: Bjerrum Ole Weis , Philip Preben , Müller‐Bérat Nicole , Hertz Henrik , Killmann Sven‐Aage
Published: August 2010

5 cases of ALL are reported with a t(4;11) chromosomal rearrangement, and 31 cases, investigated before therapy, are reviewed. The (4;11) translocation characterizes a subentity of ALL having the following main features, as compared with ALL in general: 1) Excessively poor prognosis, with a median survival of 6 months despite high remission rates. 2) Low median age of 10 months in children. 3) CNS involvement apparently occurs more frequently. 4) Median WBC is 12 times higher in adults and children, median per cent of blasts in blood 1.5 times higher in adults and 1.8 times higher in children. 5) Splenomegaly is present more frequently. 6) Surface markers are non‐B, non‐T. The incidence of t(4;11) in ALL varies greatly in the series published so far, from 0.04% to 12%.
Li+‐induced release of the folate binding protein from human granulocytes
Authors: Holm Jan , Hansen Steen Ingemann , Lyngbye Jørgen
Published: August 2010

Release of folate binding protein from human leucocytes suspended in isotonic NaCl was studied in experiments where folate binding activity of the suspending medium was determined by equilibrium dialysis (pH 7.4, 37° C) against 3H‐folate. Release from leucocytes containing particularly high concentrations of folate binding protein was significantly increased in the presence of 70 mmol/I Li+. The stimulated release was apparently not an osmotic phenomenon since no effect was observed with isomolar Na+/ K+. The released protein resembled the folate binding protein in leucocyte lysate as to characteristics of radioligand binding, ionic properties and molecular size. Hence no transformation of the protein seemed to occur during Li+‐induced release.
Therapeutic implications of mediastinal involvement in advanced Hodgkin's disease
Authors: Specht Lena , Nissen Nis I. , Walbom‐Jørgensen Sven
Published: August 2010

47 patients with advanced Hodgkin's disease (stage IIIB or IV) and mediastinal involvement, treated during the period 1969‐78 and followed till death or from 36 to 126 months after initiation of therapy, were analysed. All 47 patients had received combination chemotherapy (MOPP or equivalent regimens). 20 had also received additional radiotherapy to mediastinum (and in some cases to other involved areas as well). The 2 treatment groups did not differ significantly with regard to the more important prognostic factors. Both in the case of stages IV and IIIB patients in the group treated with combination chemotherapy alone, remissions were significantly more often only partial, the frequency of relapse and of treatment failure was significantly higher, and relapse‐free survival was significantly poorer than in the group treated with additional radiotherapy. Furthermore, survival from Hodgkin's disease and crude survival including all causes of death were significantly better for patients treated with combination chemotherapy plus mediastinal irradiation. Consequently, for patients with advanced Hodgkin's disease and mediastinal involvement a combined approach including radiotherapy as well as combination chemotherapy would seem advisable.
Myeloperoxidase‐deficient polymorphonuclear leucocytes (IV): Relation to FAB‐classification in acute myeloid leukaemia
Authors: Bendix‐Hansen Knud , Nielsen Henning Kaspersen
Published: August 2010

In 148 consecutive cases of untreated acute myeloid leukaemia (AML) the relation between an increased number of myeloperoxidase (MPO)‐deficient polymorphonuclear leucocytes (PMN) and a classification modified after the proposals outlined by the French‐American‐British Co‐operative Group, the FAB classification, was investigated. In 22 cases with minimal granulocytic component, 8 M5, 13 M6, 1 M7, no one (0%) showed an increased number of MPO‐deficient PMN. In 3 (13 %) of 23 cases with slight granulocytic component, 3 M0, 20 M1, and in 49 (57%) of 86 cases with granulocytic differentiation (53 M2, 1 M3, 32 M4), an increased number was demonstrated. This difference was statistically significant at a high level (p < 0.0001). The number of MPO‐deficient PMN could not be estimated in 15 cases of AML and 2 additional cases were mixed leukaemias. It is concluded that an increased number of MPO‐deficient PMN in acute leukaemia speaks in favour not only of AML, but suggests the diagnosis of subtypes with some granulocytic component, most likely M1, M2, M3 or M4. Furthermore, the results support the concept that in AML at least some of the mature myeloid cells may be involved in the leukaemic process.
IgG‐mediated haemolysis masquerading as cold agglutinin‐induced anaemia complicating severe infection with Mycoplasma pneumoniae
Authors: Louie Eric K. , Ault Kenneth A. , Smith Brian R. , Hardman Elaine L. , Quesenberry Peter J.
Published: August 2010

Haemolytic anaemia complicating Mycoplasma infection has usually been attributed to IgM cold agglutinins. This report describes a patient with pneumonia due to Mycoplasma pneumoniae in whom severe haemolysis persisted despite declining thermal amplitude and titre of cold agglutinins as the infection resolved. Class‐specific antiglobulin (Coombs) testing defined an IgG warm agglutinin coating the patient's erythrocytes that was distinct from the IgM cold agglutinin identified by Sephadex G‐200 gel filtration and dithiothreitol inactivation. Monoclonal IgM(γ) and IgK (k) circulating proteins were identified and immuno‐electrophoresis of the cold aggulutinin‐containing cryoglobulin fraction identified the cold agglutinin as an IgM(γ). In this patient initially presumed to have cold agglutinin induced haemolysis secondary to Mycoplasma infection, an IgG warm agglutinin was identified as the aetiology for the patient's haemolysis, underscoring the clinical relevance of careful evaluation of the mechanism of haemolysis accompanying Mycoplasma pneumonia.
Phenotypic conversion of TdT+ adult AML to CALLA+ ALL
Authors: Marcus R. E. , Matutes E. , Drysdale H. , Catovsky D.
Published: August 2010

A case of acute leukaemia is described in which the blast cells showed Sudan Black and terminal deoxynucleotidyl transferase (TdT) positivity at presentation and did not react with the monoclonal antibodies (McAb) My9 (anti‐myeloid) and J5 (anti‐CALL antigen). The myeloid lineage of these cells was confirmed by the myeloperoxidase (MPO) reaction at electron microscopic level. The patient entered complete remission but relapsed one year later with blasts showing negative Sudan Black and MPO reactions. These cells were still TdT+ but J5 was now positive. This case points to the existence of a clonogenic leukaemic cell with potential for evolution in both myeloid and lymphoid lineages. This is also suggested by the reactivity of both types of blast cells with the McAb 3C5 which recognises an antigen present both on early myeloid and lymphoid precursors. It is possible that patients with such leukaemias may benefit from combined therapy directed against cells of both myeloid and lymphoid lineages.
Hairy cell leukaemia occurring during phenytoin (diphenylhydantoin) treatment
Authors: Gyte Gillian M. L. , Richmond Joan E. , Williams J. R. B. , Atwood J. L.
Published: August 2010

We describe the case of a patient who developed hairy cell leukaemia (leukaemic reticuloendotheliosis) during phenytoin treatment. Hairy cells were identified by fluorescence, phase contrast and electron microscopy; they contained tartrate‐resistant acid phosphatase activity, formed rosettes with mouse but not sheep erythrocytes and bore monoclonal surface immunoglobulin. Because of the association of pseudo‐ and true lymphomas with phenytoin it is possible that this fymphoproliferative disorder arose as a result of the treatment with phenytoin, possibly in conjunction with sulthiame.