bluuebunny/crossref_metadata_2025 huggingface dataset:
ABBREVIATIONS. Range and clinical significance of the number of myeloid‐committed stem cells in the blood of patients with acute leukaemia in remission
Authors: Hinterberger Wolfgang , Bettelheim Peter , Höcker Paul , Lechner Klaus , Neumann Erich , Niessner Herwig
Published: August 2010

Circulating granulocyte/macrophage progenitor cells (CFU‐GM) were assayed serially during remission in 17 patients with acute leukaemia (9 ALL, 8 AML). In patients with ALL receiving cyclophosphamide, 6‐mercaptopurine and methotrexate, CFU‐GM numbers were significantly lower than in normal individuals; cycles of ‘reinduction’ chemotherapy (vincristine, prednisolone) caused a 10‐fold increase in CFU‐GM per ml of blood. In 2 ALL patients a substantial increase in CFU‐GM numbers preceded the morphologically detectable relapse. In patients with AML receiving repeated courses of cytosine‐arabinoside and 6‐mercaptopurine, circulating CFU‐GM were likewise reduced. In 6 patients who relapsed, a further reduction of CFU‐GM was seen. A complete absence of circulating CFU‐GM was observed in 10 of the 23 investigations performed within 6 weeks prior to the morphologically detectable relapse, while such a ‘zero’‐growth ooccurred in only 1 of 54 experiments performed during stable remission. In summary, in patients with ALL in remission, circulating CFU‐GM are increased following treatment with vincristine and prednisolone. In patients with AML, declining numbers of circulating CFU‐GM may predict an imminent relapse.
Prognostic factors for relapse‐free survival in childhood acute lymphoblastic leukaemia
Authors: Clausen Niels , Scheibel Elma , Nyboe Jørgen
Published: August 2010

11 variables determined at the onset of acute lymphocytic leukaemia were tested to predict disease‐free survival in 267 children. All children had received similar induction treatment and basic maintenance therapy, whereas 5 different reinforcement treatments were administered irrespective of the severity of the disease at onset. Three modes of prophylactic central nervous system treatment were employed. The risk of relapse was significantly increased for leucocyte count above 50 times 109/1, lymphoblasts above 80% in peripheral blood, age below 2 years or over 5 years, and for males. The risk of relapse was increased by estimated factors of 1.9, 2.3, 1.7, and 1.7, respectively.

When the above 4 variables were included in the model, no further prognostic value was demonstrated for haemoglobin concentration, platelet count, signs of bleeding in the skin, mucous membranes or intracranially, presence of leukaemic infiltrations outside the bone marrow, hepatosplenomegaly, mediastinal mass, or T‐ or B‐cell leukaemia. However, evaluation of T‐ or B‐lymphoblast type impact was hampered by small numbers.
Evidence for genetic effects on variation in plasma unsaturated transcobalamin II and cobalamin (vitamin B12)
Authors: Magnus Per , Magnus Erik M. , Berg Kåre
Published: August 2010

Unsaturated plasma transcobalamin II (UTC II) and cobalamin were measured in two selected age‐groups of like‐sexed mono‐ and dizygotic twins. For UTC II, a higher mean level was found in women than in men, and in the older (57 to 61 years) than in the younger (33 to 39 years) age group. Testing of genetic‐environmental models revealed that variation in plasma levels of UTC II is almost exclusively genetically determined. More than 50% of the variation in cobalamin levels was accounted for by genes, the remainder being due to person‐specific environmental factors (for older males no model gave a good fit). A negative correlation was noted between UTC II and cobalamin levels. The correlation coefficient was low, and the variation in UTC II accounted for only about 4% of the variation in the cobalamin level. This finding suggests that a pathologically high value of one of the variables may have clinical significance, regardless of the value of the other variable. For 22 patients studied longitudinally, a clear tendency to maintain plasma levels at constant levels over long periods of time was found, suggesting that certain degrees of deviation from these levels may have clinical relevance.
Prevention of Early Familial Maladjustment by Parent‐Staff Group Meetings: Influence of Familial Background
Authors: Allain J P , Bernard J P , Frommel D , Laurian Y , Proust J P
Published: August 2010

The possibility of preventing some major familial maladjustment following the diagnosis of severe haemophilia in the frame of free discussion group was explored. Five couples, 3 with a familial history of haemophilia and 2 without met 5 times over a 2 year period with 3 staff members for a full day. Transcripts of tape recorded sessions were analyzed. Parents with no familial history were apparently more affected but had a more dynamic approach towards hemophilia than the others. They benefited more from the program. Four of the five families were able to treat their child at home before 4 years of age. This new approach seems to help parents to adjust to this severe chronic disease and staff members to reconsider their interaction with parents.
A Study of Psycho‐social Aspects of Both Haemophiliacs and Carriers in Greece
Authors: Pittadaki J. , Louizou C. , Mandalaki T.
Published: August 2010

The aim of this research study was firstly to investigate the implications of the psycho‐social aspects of haemophiliacs/carriers in Greece and secondly to understand human nature and thus be able to handle haemophiliacs' and carriers' anxieties and fears.

The design and methodology of the study was an exploratory and descriptive one. The total membership was a random sample of hundred haemophiliacs and hundred carriers. Only 89 and 75 respectively answered. Two questionnaires were administered with a veiw to obtain the groups' reactions and attitudes to various psycho‐social aspects affecting their personal life and environment. The questionnaires consisted of open‐ended and closed questions. The findings from this study suggested that haemophiliacs experience pain, parental anxiety, stress in the family and interference with family plans in a more realistic and objective way. This attitude could be a result either from a genuine awareness of their disease or from the psychology of defending oneself through denial. With regard to carriers it was found that similar psycho‐social aspects had significant signs of exaggeration in terms of fear and anxiety. This could be attributed to the inappropriateness of their defensive reaction. The evaluation of the responses in the light of the actual situation, confirms the above results with an even greater emphasis on tendencies.
Assay of Factor VIII:C with a Chromogenic Substrate
Authors: Rosén S.
Published: August 2010

A chromogenic method for the determination of factor VIII:C in plasma and concentrate has been developed. Bovine factor Xa is generated in a system containing bovine factors IXa and X, Ca2+ and phospholipid. The amount of factor Xa formed is directly proportional to the amount of factor VIII:C. Thus, after hydrolysis of the factor Xa selective chromogenic substrate S‐2222, the colour produced by released p‐nitroaniline is linearly related to the concentration of factor VIII:C in the sample. Hydrolysis of the substrate by thrombin is prevented by including the thrombin inhibitor I‐2581. A major methodological advantage is the exclusion of hemophilia A plasma or artificially prepared factor VIII deficient plasma.

The detection limit is 1 per cent factor VIII:C, and the CV is lower than 5 per cent in both the earlier defined ranges, 1–20 per cent and 15 ‐ 100 per cent factor VIII:C and in the recently introduced extended range 20–150 per cent factor VIII:C. The resolution in the 15–100 per cent range is about 0.008 absorbance units per per cent factor VIII:C, allowing a good discrimination between samples containing e.g. 30–70 per cent factor VIII:C.

Comparative studies between the chromogenic assay and clotting assays have been performed in other laboratories with both plasma and concentrate samples and the correlation coefficient was in all cases ≥ 0.92.
Calculations of Factor VIII in vivo Recovery and Half‐life
Authors: Kjellman H.
Published: August 2010

In vivo recovery. Differences between laboratories depend on the time of sampling, factor VIII:C assay method, factor VIII:C plasma standard and the calculation of the patients' plasma volume. The results depend on whether the manufacturer's labelled potency or the factor VIII:C potency of the laboratory is used. In some countries the vials are labelled with a nominal potency ± 20 percent.

Half‐life. Most publications have shown that the factor VIII:C activity‐time curve fits a two‐compartment model. The elimination half‐life is about 12 h. The initial half disappearance time or distribution half‐life is used by some authors. However, very often the half‐life has not been defined. The data collection period has been too short and the formula for the calculation has not been presented. The large intersubject variability may be due to the quality of the data collection and analysis. There are many pitfalls in deriving pharmacokinetic variables. Do we need a pharmacokinetic model, and, if so, which one?
The Use of Laser Beams for Operations in Haemophilia
Authors: Hefti F. , Morscher E. , Koller F.
Published: August 2010

Laser beams are light rays of particular intensity. They can concentrate extremely high energies in a minimum of space and time. Since 1978 we use a “Sharplan 791 CO2 ‐Surgical Laser” for operations on haemophilacs. The edges of the Laser incision show a minimal zone of necrosis, which is sufficient to coagulate the small vessels and to reduce bleeding considerably. Until now we have carried out 21 operations on haemophilic patients with the use of Laser beams. They include 5 synovectomies of the knee joint, 4 synovectomies of the elbow (3 of them with excision of the radial head), 2 excisions of haemophilic pseucotumors, 2 joint fusions, 1 total hip replacement and 7 smaller operations. Our experiences have been favorable up to now. Due to the good haemostasis considerably less antihaemophilic factor VIII is required. In mild haemophilia Laser surgery even enables us to do without substitution at all in some cases. In severe haemophilia it is, of course, impossible to avoid postoperative bleeding. Post‐operative substitution, however, can be reduced in dose and duration by 50 percent on average.

Considering the invaluable advantage of being able to perform almost “bloodless” operations on haemophiliacs with Laser beams, the disadvantages of the technique ‐ such as the complicated manipulation of the apparatus ‐ are of minor importance.
Decreased Helper‐Suppressor Cell Ratios Following Treatment with Blood Products: Factor VIII and IX Concentrates and Fresh Frozen Plasma
Authors: Ragni M V , Lewis J H , Spero J A , Bontempo F A , Rabin B S
Published: August 2010

The immunologic status of three groups of multiply‐transfused asymptomatic patients was evaluated. These included five with acquired inhibitors to factor VIIi treated with both factor VIII and factor IX concentrates (group A), seven with hemophilia B treated with factor IX concentrate (group B), and six with hemophilia B treated with fresh frozen plasma (group C). Mean T helper/T suppressor cell ratios (± S.E.M.) for the three groups were 0.72 ± 0.09, 1.35 ± 0.18 and 1.37 ± 0.12, respectively. All three differed significantly (p < 0.01) from the control mean ratio of 2.22 ± 0.16. In addition the mean ratio of group A patients was significantly different (p < 0.01) from that of groups B and C. An inverted ratio (< 1.00) was found in all group A patients and only one group B patient. An elevated IgG was found in 80 percent, 57 percent and 5 0 percent of each group, respectively. These immunological findings bear a striking resemblance to those of the acquired immunodeficiency syndrome (AIDS) of homosexuals, intravenous‐drug abusers, Haitian immigrants, and factor‐VIII‐concentrate‐treated hemophiliacs. Transmission via a blood borne infectious agent seems likely.
An Immunologic Study of Spouses and Siblings of Asymptomatic Hemophiliacs
Authors: Ragni M V , Bontempo F A , Lewis J H , Spero J A , Rabin B S
Published: August 2010

A transmissable agent may be responsible for the recent occurrence of the acquired immune deficiency syndrome (AIDS) in female heterosexual partners and infant contacts of AIDS victims or of persons at increased risk for AIDS. We, therefore, evaluated the clinical and immunologic status of 18 hemophiliac‐spouse pairs and 19 hemophiliac‐sibling pairs. Using surface marker assays of lymphocyte subpopulations, we found a mean T helper cell/T suppressor cell (H/S) ratio ± S.E.M. in 18 hemophiliac adults of 1.11 ± 0.15 (eleven <1.00), in their 18 spouses of 1.88 ± 0.13 (none <1.00), in 19 hemophiliac children of 1.54 ± 0.11 (three(<1.00), and in their 19 siblings of 1.87 ±0.11 (none< 1.00). Both hemophiliac adult and hemophiliac children mean H/S ratios differed significantly (p < 0.05) from the control mean ratio of 2.22 ± 0.16 and from the mean of their respective non‐hemophiliac spouse or sibling group (p < 0.05). The mean ratio of hemophiliac adults differed significantly from that of hemophiliac children (p < 0.05). These findings suggest that lymphocyte alterations in hemophiliacs are secondary to their therapy, are not influenced by genetic factors, and are not related to an infectious agent that is easily transmissable by close contact.
Ecology of Wound Healing in the Oral Cavity
Authors: Gustafson G T
Published: August 2010

Wounds heal by a series of events controlled by an information flow from the organism as a whole to the wound and from cell to cell during the healing process. This information is mediated by many signals. Thrombin and factor XIIIa, for example, beside their coagulation effects also function as a mitogen and a cross‐linking agent for many types of proteins respectively. Beside their role in primary hemostasis, blood coagulation and clot retraction, platelets contain factors in their α‐granules (PDGF, PF4, β TG) which, at nM concentration, are chemotactic and mitogenic for cells invading the wound. Macrophages not only phagocytose damaged tissue and bacteria but also produce and secrete coagulation factors, activators and inhibitors of plasminogen activation, collagenase, lysosomal enzymes as well as fibronectin and a potent mitogenic factor. Growth factors produced outside the wound (e.g. somatomedins, EGF and other peptides produced in salivary glands) also stimulate wound healing. Finally the sequential appearance of different “structural” proteins during tissue repair has a regulating effect. It is suggested that it is time to make clinical use of the new basic knowledge accumulating in this field.
Local Fibrinolysis in the Oral Cavity
Authors: Björlin G
Published: August 2010

In vitro tissue culture has shown that plasminogen activators are released both from normal and from pathological mucous membrane in the oral cavity. Immunological study (Ljungnér et al 1983) has shown that the plasminogen activators in the mucosa of the mouth are not urokinase in character.

Increased local fibrinolytic activity, causing post‐operative bleeding, is a serious complication in patients with hemophilia or other bleeding disorders. The occurrence of pathologically increased local fibrinolytic activity can be prevented and the risk of post‐operative bleeding reduced by the administration of epsilon‐amino‐caproic acid (EACA) or tranexamic acid (AMCA). In 72 hemophilia patients, from whom 191 teeth were extracted, satisfactory results were achieved with but a simple dose of factor VIII and IX per patient in combination with the administration of tranexamic acid.

In connection with oral surgery in a number of paitents with mild hemophilia A or mild von Willebrand's disease, the synthetic vasopressin derivative DDAVP has been used instead of factor concentrate. In connection with tranexamic acid, it enabled teeth to be extracted without any post‐operative bleeding complications.
Report on First International Workshop of Pediatric Management in Hemophilia
Authors: Hilgartner M
Published: August 2010

The first meeting of the Pediatric Advisory Committee, those pediatricians interested in the care of the child with hemophilia, took place in Pomerio, Italy, in November, 1982. The participants were from Holland, France, Denmark, Sweden, United Kingdom, Germany, Spain, Italy and the United States. In the first session the participants discussed the pediatric care in each of their countries and how it interdignitated with the hemophilia care. There was consistency in that all countries had a system of comprehensive care and a home care program within that system. The major topic of discussion was the use of prophylaxis: the criteria for entering patients on a prophylactic program, the protocol for treatment, the evaluation of efficacy of the program and the risks of long term therapy on the physical, immunologic, and the psychological functioning of the patient. It was agreed that an in‐depth prospective study needs to be done to compare the outcome of children on prophylaxis to those on‐demand therapy. The role of the pediatrician in the growth and development and the hematologic care of the children was explored and found to vary widely from country to country both in the Centers and in liaison with the local physicians. There was no consistency in family support or learning of coping skills. Problems in care for the adolescent were universal. Neither the hematologic nor the psychosocial problems specific to this age group are well addressed and the liaison with the internist needs to be expanded to fully service the growth and maturation of the young man. In summary, we believe that the role of the pediatrician as primary care physician and hematologist for the child and the adolescent needs to be expanded to improve the mental and physical development of the patient with hemophilia.
Worldwide Overview of Plasma Procurement and Fractionation
Authors: Britten A.F.H. , Ala F. , Carman C. , Sibinga C.Th. Smit
Published: August 2010

Purpose — Information has been gathered to address the question of why factor VIII products are in short supply in many countries.

Methods — A questionnaire was sent to 59 member countries of the World Federation of Hemophilia (WFH) by WFH Task Force II; 43 replies were received. Previously published data supplements the information thus obtained.

Results — The world's plasma supply is predominantly commercial and is not adequate. More than half of the world's plasma is commercially collected in the USA by plasmapheresis. This source accounts for approximately 80 percent of the world's factor VIII concentrates. Fractionation of approximately 7 million liters of plasma occurs each year; fractionation capacity is far greater than this. There are approximately 80 fractionation facilities, but 7 major companies account for more than half the total capacity. Six of these seven are, or have been. active in the USA. Expansion of commercial fractionation is limited only by regulatory controls and the availability of money. Availability of factor VIII products is inadequate in almost all countries. Only the USA has clear self‐sufficiency. Multiple factors affect accessibility of individual patients to effective treatment.

Conclusion — There is a serious worldwide shortage of factor VIII products. Satisfactory resolution will require technologic advances or enormous expense.
FACTOR VIII ASSAY PROFICIENCY ASSESSMENT: EXPERIENCE IN THE UK
Authors: Thomson Jean M. , Poller Leon
Published: August 2010

ABSTRACT: Factor VIII:C assays have been regularly included in the UK (NEQAS) in blood coagulation programme since 1980. Test plasmas with mild or moderate defects of Factor VIII:C, together with plasmas containing normal Factor VIII:C levels have been included. The aim in their selection has been to provide sufficient challenge to ascertain the reliability of individual laboratories' Factor VIII:C assays. Centres employing uncalibrated “home‐pool” reference plasmas have obtained significantly lower results than users of the British Standard, on plasmas with Factor VIII:C levels within the normal range. The majority (almost 90%) of participants employ a one‐stage assay technique. Results on normal plasma using a two‐stage technique have been significantly lower than those performed by a one‐stage method. There were no consistent differences between results obtained with manual and automated techniques. Results with Dade reagent have been significantly higher than those from other phospholipid reagents, when the Factor VIII:C content has been normal. The definition of poor performance in Factor VIII:C assays is under active consideration. Various statistical approaches are suggested but the importance of the clinical relevance of the results must be taken into account in any such definition.
FACTOR VIII ASSAY PROFICIENCY ASSESSMENT: EXPERIENCE IN THE USA
Authors: Maas Robert L. , Triplett Douglas A. , Tholen Dan
Published: August 2010

ABSTRACT: Data from the College of American Pathologists (CAP) surveys for Factor VIII:C assays from 1976–1982 are reviewed. The different instrument‐reagent combinations are analyzed according to precision and sensitivity. The results of questionnaires on specific assay technic are also analyzed. There has been an increase in the number of laboratories performing the Factor VIII:C assay from 1976 to 1982. In general there was poor correlation between precision and sensitivity in most systems; however, newer instrument‐reagent combinations from the same manufacturer have shown improvement in precision‐sensitivity ratings. Questionnaire results revealed marked interlaboratory variation with respect to the technical aspects of factor assays. Recent introduction of recommended Factor VIII:C assay guidelines, international standards for Factor VIII:C concentrate and plasma, and newer, more precise instrument‐reagent combinations should improve laboratory performance in Factor VIII:C assays.
Density distribution of chronic myeloid leukaemia and normal colony‐forming cells in diffusion chambers (CFU‐D) and agar (CFU‐GM)
Authors: Nilsson Bo , Olofsson Tor
Published: August 2010

The density distribution in Percoll gradients of clonogenic cells forming colonies in diffusion chambers (CFU‐D) or in agar culture (CFU‐GM) was studied in chronic myeloid leukaemia (CML). The density distribution of CFU‐GM in CML was homogeneous with peaks within 1.058–1.061 g/ml, which is slightly lower than normal. CFU‐D, on the other hand, showed heterogeneous distributions both in CML and in normal controls. Two separable populations of CFU‐D were recognized, one with the same or lower density than CFU‐GM that formed almost exclusively neutrophilic colonies in diffusion chambers, and a second population concentrating in the density range 1.068–1.075 g/ml which primarily formed macrophage colonies. The second population contained colony‐forming cells derived from both Fc‐receptor positive and Fc‐receptor negative precursor cells, suggesting that at least some colonies in diffusion chambers arise from Fc‐receptor positive granulopoietic cells of intermediate maturity and/or monocytes. The concentration of CFU‐D in peripheral blood was increased 40‐ to 100‐fold in 2 patients currently off treatment who had increased WBC counts.
DIAGNOSIS OF IRON DEFICIENCY
Authors: Rybo Elisabeth
Published: August 2010

Haematological variables were studied in a randomised population sample of 372 38‐year‐old women resident in Gothenburg, Sweden during the period 1968–69. The participation rate was 91.4 %. The study was performed to evaluate the laboratory diagnosis of iron deficiency. The haematological investigation included determination of haemoglobin concentration, erythro‐cyte and reticulocyte counts, serum iron concentration, total iron binding capacity, packed cell volume, sternal bone marrow aspiration with estimation of stainable iron in the reticuloendothelial cells, sideroblast count, iron absorption test with 59Fein a whole‐body counter and determination of menstrual blood loss. Serum ferritin concentrations were later determined on samples which had been frozen for 10 years. Eighty‐nine women with no or only traces of reticuloendothelial iron in the bone marrow completed a double‐blind supplementation trial, in which iron and placebo therapy were compared.

Determination of stainable iron in the reticuloendothelial cells of the bone marrow was used as a direct method for the evaluation of iron stores. In 31.5 % of the women there was no reticulendothelial iron and in 14.3 % there were only traces. Of the indirect methods compared with the bone marrow method the serum ferritin concentration and iron absorption gave the highest correlations. A high correlation was also observed between menstrual blood loss and the content of reticuloendothelial iron. An arbitrarily chosen scale for the estimation of the amount of stainable reticuloendothelial iron in the bone marrow was used for these correlation analyses.

The differences in mean corpuscular haemoglobin, transferrin saturation, sideroblast count, iron absorption, and menstrual blood loss were all highly statistically significant when the series of women with no or only traces of reticuloendothelial iron in the bone marrow were compared to those with clearly visible or abundant amounts of stainable iron. There were no significant differences concerning these variables between women who had no traces of stainable iron and those who had only traces of stain‐able iron. Increased iron absorption was found in women with a lack of stainable iron in the reticuloendothelial cells compared to women with stainable iron, irrespective of sideroblast count.

The results from the iron supplementation study indicates that the haemoglobin concentration values of many of the women, although being within the normal range, were suboptimal for the individual woman. However, we considered it not possible to ascertain which women were responders to iron therapy, as a comparison between the effects of iron and placebo could not be made for the individual subject.

According to multivariate analysis, determination of serum ferritin concentration was the most valuable indirect method for the diagnosis of depleted iron stores, and we are of the opinion that serum ferritin determination may replace bone marrow examination in the diagnosis of iron deficiency in women with or without anaemia who are otherwise healthy.
EFFECT OF IRON SUPPLEMENTATION TO WOMEN WITH IRON DEFICIENCY
Authors: Rybo Elisabeth , Bengtsson Calle , Hallberg Leif , Odén Anders
Published: August 2010

The response to iron therapy in 38‐year‐old women was studied in an iron supplementation trial. Women with no or only traces of reticuloendothelial iron in bone marrow samples received in a double‐blind fashion tablets containing 37 mg ferrous iron or placebo three times daily. The women in the iron supplementation group increased significantly more their haemoglobin concentration and packed cell volume than the women in the placebo group. The average increase in haemoglobin concentration was 7.5 g/l. Approximately 75 % of the women in the iron supplementation group increased their haemoglobin concentration in spite of the fact that only 20 % had pretreat‐ment concentrations below 120 g/l. We found no differences in change of haemoglobin concentration, packed cell volume, serum iron concentration, total iron binding capacity or transferrin saturation between subjects with no reticuloendothelial iron and women with only traces of reticuloendothelial iron. We considered it impossible to define “responders” to iron therapy in an acceptable way by means of the iron supplementation test described in this paper.
Identification of non‐T non‐B lymphocyte leukaemia patients with favourable prognosis by cell surface glycoprotein analysis
Authors: Siimes Martti A. , Andersson Leif C. , Gahmberg Carl G.
Published: August 2010

Leukaemic cells from 15 children with ALL were isolated and their surface glycoproteins labelled with 3H after treatment with neuraminidase and galactose oxidase followed by NaB3H4. The labelled glycoproteins were separated by polyacrylamide slab gel electrophoresis and visualized by flourography. The cells could be classified into four groups: 1) Surface glycoprotein pattern resembling that of normal T lymphocyte (one patient); 2) Surface glycoprotein pattern showing some T cell characteristics (5 patients); 3) Surface glycoprotein profile with strongly labelled glycoproteins of apparent molecular weight of 120 000 and 130 000, and frequently a glycoprotein with an apparent molecular weight of 210000 and visible HLA‐coded glycoproteins (6 patients); 4) Surface glycoprotein pattern not resembling those of the other groups (3 patients).

Follow‐up showed that patients in group 3 have remained in their initial remission (5/6) for the complete study period of 5–6 yr, whereas all patients in the other groups have relapsed and/or died. We conclude that the surface glycoprotein analysis enables the identification of patients with non‐T non‐B ALL with favourable prognosis.
Acquired factor X and antithrombin III deficiency in a patient with primary amyloidosis and nephrotic syndrome
Authors: Quitt Miriam , Aghai Esther , David Miriam , Kohan Ricardo , Ari Yaakov Ben , Froom Paul
Published: August 2010

A 45‐year‐old man with primary amyloidosis was initially seen with nephrotic syndrome. Factor X was found to be 5% and antithrombin III (AT III) 45% of normal plasma values. During an 11‐month period, despite severe factor X deficiency, the patient did not have any bleeding complications. He developed progressive renal failure and AT III levels increased to normal, at which time he developed severe bleeding complications. These findings suggest a protective role of AT III deficiency against bleeding in a patient with severe factor X deficiency.
Myeloperoxidase‐deficient polymorphonuclear leucocytes (V): Relation to FAB‐classification and neutrophil alkaline phosphatase activity in primary myelodysplastic syndromes
Authors: Bendix‐Hansen Knud , Kerndrup Gitte
Published: August 2010

In 45 cases of primary myelodysplastic syndrome; 16 refractory anaemia (RA), 11 RA with ring sideroblasts (RA+), 13 RA with excess of blasts (RAEB), 5 chronic my‐elomonocytic leukaemia (CMML), the relations between myeloperoxidase (MPO) activity in polymorphonuclear leucocytes (PMN), neutrophil alkaline phosphatase (NAP) activity, absolute number of PMN and thrombocytopenia were investigated. 11 patients (26%) showed abnormal numbers (>4%) of MPO‐deficient PMN and 27 (75%) showed abnormal NAP activity (NAP score; >134.0, <15.0), mostly decreased. No significant correlations between MPO activity and NAP activity were demonstrated, nor were any significant correlations found with the other parameters investigated. The FAB‐subtypes, RAEB and CMML, showed a significant correlation to thrombocytopenia (p=0.028) and to pancytopenia (p=0.024). The findings may support the view that at least some of the myelodysplastic syndromes may be fundamentally the same disease as acute myeloid leukaemia.
Aggressive combination chemotherapy in multiple myeloma. A multicentre trial
Authors:   Finnish Leukaemia Group, Palva I. P. , Ahrenberg P. , Almquist A. , Ala‐Harja K. , Apajalahti J. , Hallman H. , Hänninen A. , Ilvonen M. , Järvenpää E. , Järventie G. , Kilpi H. , Koistinen S. , Koivunen E. , Korpi E. , Kätka K. , Lahtinen R. , Laitinen A. , Lehtinen M. , Mäkelä H. , Oivanen T. , Pelliniemi T.‐T. , Pulli T. , Rosengård S. , Rajamäki A. , Tiilikaninen J. , Timonen T. , Waris E. , Wasastjerna C. , Vilpo. J.
Published: August 2010

A one‐armed multicentre trial was conducted in Finland during the period from Jan. 1979 to Feb. 1980 to document the possible beneficial effect of aggressive combination chemotherapy MOCCA on the remission induction and survival in multiple myeloma. The regimen MOCCA consisted of vincristine, methylprednisolone and 3 alkylating agents. Of the 50 patients eligible for the for study, 39 (78%) achieved at least a 50% response. 27 (54%) achieved an excellent response. The median survival time for all patients was 49 months from the initiation of the treatment, but 23 of the 33 patients whose myeloma protein had shown a ≥ or ≧ 75% reduction were still alive at 4 yr. Advanced clinical stage and irreversible renal damage had a negative prognostic value. After 12 months on regimen MOCCA the patients with a ≧ or ≥ 75% reduction in myeloma protein were allocated at random to receive MOCCA courses bimonthly or no further chemotherapy. The maintenance chemotherapy did not prolong remission or survival.
Evaluation of neutrophil alkaline phosphatase (NAP) activity in untreated myeloproliferative syndromes and in leukaemoid reactions
Authors: Bendix‐Hansen Knud , Bergmann Olav Jonas
Published: August 2010

Neutrophil alkaline phosphatase activity was estimated in 194 patients; 59 cases of chronic myeloid leukaemia (CML), 42 cases of polycythaemia vera (PV), 24 cases of primary myelofibrosis, 7 cases of idiopathic thrombocythaemia, 6 cases of leukaemoid reaction, 19 cases of secondary polycythaemia (PS) and 37 cases of the primary myelodysplastic syndrome (MDS). According to NAP activities the groups proved to be separate entities (p < 0.00025). The incidence of decreased NAP score in the CML group was 85% and differed significantly from the other groups as a whole, as well as separately (p< 0.001). The MDS group, the only group besides CML that showed decreased scores, also differed significantly from the others (p < 0.001). The PS group, nearly always showing normal scores, differed significantly from the PV group (p<0.0052). A method evaluating single cell NAP activity proved superior to the score method in discriminating between the different groups. Thus, the incidence of decreased activity in the CML group was 93 % compared with 85% by the score method and the incidences of increased activity in the PV, MP, IT, and LR groups were 79% to 100% compared with 25% to 67% by the score method. The latter difference was statistically significant (p=0.029).
Plasma fibronectin in acute myeloid leukaemia
Authors: Petersen Erik la Cour , Ørntoft Torben , Jensen Jens Herman , Nielsen Hans Kræ;mmer
Published: August 2010

In 13 patients with acute myeloid leukaemia (AML), plasma fibronection (P‐FN) was measured before, during and after chemotherapy. Pre‐treatment concentrations of P‐FN were within the reference range and significantly higher than the nadir value (p < 0.05). A rise in body temperature by more than 1°C induced a significant fall in P‐FN (p <0.05) and transfusion with freshly drawn blood products could prevent this fall. P‐FN concentrations were significantly higher in patients obtaining complete haematological remission than in patients in whom remission could not be induced (p < 0.001). This difference could not be attributed to transfusion or febrile episodes.
Prognostic significance of architectural patterns in non‐Hodgkin lymphomas
Authors: Schultz Henrik B. , Ersbøll Jens , Hougaard Philip
Published: August 2010

Clinical data and lymphoma biopsies were analyzed in 651 patients with non‐Hodgkin lymphoma in order to describe the prognostic influence of different grades of follicular architecture compared to diffuse architecture. The follicularity was graded qualitatively according to the distinctness of the pattern (intra‐follicular, infiltrative follicular and traceably follicular patterns). The partially follicular pattern, with co‐existence of follicular and diffuse areas in the same biopsy, was graded quantitatively according to the proportion of these areas. The median survival of patients with diffuse pattern was 1.2 years, while that of patients with follicular patterns ranged from 2.5 to 7.3 yr. The prognosis for those with partially follicular pattern was not affected, whether or not more or less than 50% of the lymphoma was diffuse. For cytologically identical lymphomas, only the intra‐ and infiltrative follicular patterns influenced the prognosis favourably. This conclusion was further substantiated by means of multivariate analysis.
Chronic T cell lymphocytosis with large granular lymphocytes of helper (OKT4) phennoype
Authors: Berrebi Alain , Talmor Monica , Vorst Eljakim J. , Shtalrid Mordechai , Polliack Aaron , Nir Emanuel
Published: August 2010

A 54‐year‐old asymptomatic male patient was followed for more than 7 y and presented a constant T cell lymphocytosis without skin involvement or bone marrow depression. No clinical or haematological aggravation was noted during this follow‐up. Morphologically, the cells were large granular lymphocytes strongly positive for beta‐D‐glucuronidase, negative for acid phosphatase and with features of T cells on transmission and scanning electron microscopy. The immunological studies of the lymphocytes showed the following parameters: E rosettes+, mouse rosettes‐, SmIg‐, OKT3+, OKT4 +, OKT8‐, OKT6‐, Ia‐, TdT‐, NK‐, HTLV‐, decreased PHA and PWM stimulation, no interleukin 2 production and failure to enhance Ig synthesis in a PWM driven system. The karyotype was normal. This case of chronic T cell lymphocytosis with large granular lymphocytes helper profile and defect of helper function, not reported in the literature, may correspond to a distinct entity in the heterogeneous group of chronic T cell disorders.
Predictive value of bone marrow cultures in 48 patients with acute myeloblasts leukaemia or myelodysplasia both secondary to treatment of other malignant diseases
Authors: Mortensen B. Thing , Pedersen‐Bjergaard J. , Pedersen N. Tinggaard , Westrup M. , Ersbøll J. , Philip P. , Nissen N. I.
Published: August 2010

The growth pattern of bone marrow cells in agar cultures was studied in 48 patients with acute myeloblasts leukaemia or myelodysplasia, secondary to cytoreductive treatment, and compared to other laboratory findings. At diagnosis the status of the patients was: acute myeloblastic leukaemia (AML) in 9, acute myeloproliferative syndrome (AMS) in 13 and preleukaemic syndrome (PL) in 26 patients. 20 of the 39 patients with AMS and PL developed acute leukaemia, 15 of them within 1 year. 15 died of complications to cytopenia and only 4 are still alive and without leukaemia, observed from 8 to 55 months.

Progression to AML was predicted from the agar cultures by increased cluster growth. Among 18 patients with increased cluster growth at diagnosis 14 subsequently developed AML. Among 21 patients with normal or decreased cluster growth at diagnosis 6 patients developed AML, but after conversion of the growth pattern to increased cluster growth. In 2 patients the increased cluster growth disappeared spontaneously and the patients are long‐term leukaemia‐free survivors.

Colony growth pattern, conversely, was not related to leukaemic progression. Only 1 patient had normal growth pattern at diagnosis with respect to both clusters and colonies. Survival was short, with a median of about 7 months, unrelated to growth pattern and leukaemic progression.
Myelopoiesis and erythropoiesis of bone marrow cells cultured in vitro in patients recovered from aplastic anaemia
Authors: Ruvidić R. , Jovčić G. , Biljanović‐Paunović L. , Stojanović N. , Mijović A. , Pavlović‐Kentera V.
Published: August 2010

Methylcellulose culture assay was used to detect committed haemopoietic stem cells, CFU‐C and CFU‐E, in aplastic anaemia patients with autologous haemopoietic reconstitution. Severe diminution of CFU‐C was found in all the patients studied and the absence of a dose‐response to colony stimulating factor (CSF) was demonstrated. A reduced number of CFU‐E and lower erythropoietin (Ep) sensitivity of those progenitors was detected as well. Autologous serum added to the bone marrow cultures of these patients enhanced the growth of CFU‐C but inhibited CFU‐E growth. According to the results presented, some residual damage at the stem cell level is suggested.
Cyclosporine A in a case of refractory severe aplastic anaemia
Authors: Seip M. , Vidnes J.
Published: August 2010

A boy, born in 1975, developed severe aplastic anaemia in 1982. Treatment with oxymetholone plus corticosteroids and later bolus methylprednisolone was ineffective. Following a 5‐d course with antithymocyte globulin, a partial remission was achieved, but thrombocytopenia necessitating platelet transfusions every 10–14 d persisted. Under treatment with cyclosporine A the thrombocytopenia improved markedly, and there is no need for further transfusions. These observations combined with those reported in another case of aplastic anaemia by Stryckmans et al (1) indicate that cyclosporine A may be of value in some cases of aplastic anaemia.
Acid hydrolase activities in B cell chronic lymphocytic leukaemia lymphocytes: Correlation of cytochemical reactions with immunological phenotype
Authors: Crockard A. D. , Macfarlane E. , Markey G. M. , McConnell R. E. , Alexander H. D. , Agnew A. N. D. , Morris T. C. M. , Bridges J. M.
Published: August 2010

The cytochemical reactions of 5 acid hydrolases, α‐naphthyl acetate esterase (ANAE), acid phosphatase (AP), β‐glucuronidase, β‐glucosaminidase and dipeptidylaminopeptidase IV (DAP IV) were investigated in lymphocytes from 30 patients with B cell chronic lymphocytic leukaemia (B‐CLL). Based on ANAE and AP reactivities, 4 cytochemically distinctive subgroups were identified: Group 1: AP and ANAE < 50% positive lymphocytes (5 cases); Group 2: AP > 50%, ANAE < 50% positive lymphocytes (11 cases); Group 3: AP < 50%, ANAE > 50% positive lymphocytes (7 cases); Group 4: AP and ANAE > 50% positive lymphocytes (7 cases), β‐glucuronidase displayed similar patterns of reactivity to AP. β‐glucosaminidase activity was observed in the majority of lymphocytes in most patients, whereas DAP IV activity was present in < 20% of lymphoid cells. The study failed to establish any relationship between cytochemical grouping and patients' clinical status, peripheral lymphocyte counts, E or mouse rosette values, light or heavy chain cellular immunoglobulin (Ig) class. Attempts to correlate acid hydrolase and Ig heavy chain isotype expression, putative markers of B cell maturation, were unsuccessful and indicate that within the narrow spectrum of B cell differentiation seen in B‐CLL these characteristics are unrelated.
Anti‐fibrinolytic therapy with aminocaproic acid for the control of bleeding in thrombocytopenic patients
Authors: Garewal Harinder S. , Durie Brian G. M.
Published: August 2010

11 courses of EACA were given to 9 acutely ill, severely thrombocytopenic patients (platelet count < 20 × 109/1). 6 patients were being treated for acute leukaemia while 1 each had cyclical amegakaryocytic thrombocytopenia, dysmyelopoietic syndrome and advanced chronic lymphocytic leukaemia. 8 were refractory to HLA‐matched platelets and 1 refused blood product transfusion. All had simultaneous major medical complications such as infection and granulocytopenia. The highest dose of EACA used was 24 mg/d. Improvement in haemostasis was noted in all patients with successful control of epistaxis in 1, control of gastrointestinal bleeding in 3 and lack of significant bleeding for 4–29 d in the remaining 5 patients. The only toxicity was dose‐related nausea. Since this patient group was at extremely high risk for haemorrhage, we conclude that EACA is safe and useful in the management of thrombocytopenia including that occurring during leukaemic induction.
Essential cryoglobulinaemia: A clinical course lasting 25 years
Authors: Petersen Jan
Published: August 2010

The clinical course of a patient is described whose primary manifestations of a circulating cryo IgGK were cutaneous symptoms of pain, vascular purpura and necrotic ulcerations, especially of the lower extremities. A biopsy specimen of skin lesions showed vasculitis and immune reactants in the vessel walls. The aetiology was not recognized. The effect of primary long‐term therapy with prednisone was not essential. Combined therapy with cyclophosphamide and plasmapheresis allowed a satisfactory initial remission but had to be maintained repeatedly in order to reduce the periodic recurrence of clinical signs and symptoms. Renal failure terminated the clinical course at 25 years from onset of symptoms.
Serum procollagen III peptide in chronic myeloproliferative disorders
Authors: Hasselbalch Hans , Junker Peter , Lisse Ida , Bentsen Kirsten D.
Published: August 2010

Using a radioimmunoassay the serum concentration of the N‐terminal propeptide of type III procollagen (P‐III‐P) was measured in 35 patients with chronic myeloproliferative disorders, including idiopathic myelofibrosis (n = 10), osteo‐myelosclerosis (n = 4), transitional myeloproliferative disorder (n = 5), polycythaemia Vera (n = 10) and chronic myelogenous leukaemia (n = 6). The normal range in 35 healthy controls was 4.9–11.7 ng/ml. The serum concentration of P‐III‐P increased with increasing degrees of bone marrow reticulin fibrosis. By contrast, almost normal levels were detected in osteomyelosclerosis with an indolent clinical course, in which an excessive deposition of mature collagen fibres was found, representing mainly type I collagen. These observations indicate that the serum P‐III‐P level is positively correlated to the degree of bone marrow reticulin fibrosis, whereas levels are near normal in patients with osteomyelosclerosis and stable disease. Measurement of serum P‐III‐P may be a useful indicator of disease activity in rnyelofibrosing conditions.
Thrombocytopenia with thrombocytopathy possibly related to abnormalities of intracellular Ca+ + fluxes and followed by the development of leukaemiaxs
Authors: Bellucci S. , Levy‐Toledano S. , Maclouf J. , Rendu F. , Tobelem G. , Caen J. P.
Published: August 2010

A patient is described who presented a thrombocytopenia with thrombocytopathy followed by the development of a leukaemia. The disorder was characterized by decreased aggregation in the presence of ADP, and a lack of aggregation in the presence of arachidonic acid, natural endoperoxide or collagen. In parallel, 14C‐serotonin release was severely decreased or nil in response to these inducers. Thrombin induced a slightly decreased aggregation and a normal 14C‐serotonin release. Thromboxane B2 (T × B2) synthesis was normal after stimulation by arachidonic acid, natural endoperoxide or thrombin showing a normal arachidonate metabolism. In addition, the mepacrine test showed no significant decrease of the number of dense bodies with an average of 4.6 per platelet (versus 5.4 ± 0.8 sd in controls). Stimulation by ionophore A 23187 failed to induce aggregation, 14C‐serotonin release, or T × B2 synthesis. Furthermore, in the presence of EDTA, A 23187 did not provoke activation as reflected by 14C‐serotonin release or T × B2 synthesis. Thus, in this case of thrombocytopathy, the hypothesis of abnormal intracellular Ca+ + fluxes responsible for the defective platelet release phenomenon, was suggested.
Platelet peroxidase of circulating thrombocytes in acquired refractory anaemias
Authors: Woessner S. , Lafuente R. , Florensa L.
Published: August 2010

The platelet peroxidase (PPO) content of circulating thrombocytes was determined in 10 healthy controls and in 18 cases of acquired refractory anaemia (2 with refractory anaemia, 4 with sideroblastic refractory anaemia, 8 with refractory anaemia with excess of blasts, 3 with refractory anaemia in transformation and 1 with chronic myelomonocytic leukaemia). The thrombocytes of the controls were invariably PPO‐positive. No peroxidase deficiency was found in the 4 patients with sideroblastic refractory anaemia. Of the remaining 14 cases PPO‐positive and PPO‐negative thrombocytes coexisted in 8. Only in 1 case of refractory anaemia with excess of blasts were circulating platelet peroxidase‐positive micromegakaryocytes demonstrated. PPO deficiency seems to be an important dysthrombopoietic feature detectable only at an ultrastructural level.