bluuebunny/crossref_metadata_2025 huggingface dataset:
M‐2 protocol for melphalan‐resistant and relapsing multiple myeloma
Authors: Cavo Michele , Galieni Piero , Tassi Cristina , Gobbi Marco , Tura Sante
Published: July 2010

33 patients with advanced refractory multiple myeloma received a combination of vincristine, cyclophosphamide, carmustine, melphalan and steroids (M‐2 protocol). 20 of them had failed prior chemotherapy with alkylating agents and the remaining 13 patients had relapsed after a response to these drugs. An objective tumour cell mass reduction (≥ 50%) was achieved in 17% of the patients (6% of previously nonresponders and 33% of previously relapsing), while 9 additional patients improved (30–50% tumour reduction), for an overall response rate of 47% (39% for previously nonresponders and 58% for previously relapsing). The median duration of response was 7 months. Thrombocytopenia was the most common toxicity encountered in the study (39% of cases). Our findings indicate that M‐2 protocol is an effective salvage treatment for patients who relapse from previous chemotherapy with alkylating agents. In contrast, results in patients who are primarily resistant to these drugs justify the search for different treatment programmes which can produce greater degrees of tumour reduction.
The deoxyuridine suppression test performed on phytohaemagglutinin‐stimulated peripheral blood cells fails to reflect in vivo vitamin B12 or folate deficiency
Authors: Matthews J. H. , Wickramasinghe S. N.
Published: July 2010

Because phytohaemagglutinin‐stimulated lymphocytes acquire folate deficiency in vitro, we have re‐examined the claim that the deoxyuridine suppression test (dU‐test) based on such cells helps to diagnose megaloblastic states. dU‐test results were obtained from the phytohaemagglutinin‐stimulated blood cells of 77 patients at 6 concentrations of dU. 21 megaloblastic patients with cobalamin or folate deficiency did not have a mean blood dU‐test result significantly higher than that of 21 normoblastic patients at any concentration of dU. Among all patients, however, there was a weak correlation between the blood and marrow dU‐test results. Folic acid corrected the blood dU‐test results more in the normoblastic than the megaloblastic patients, and a difference between the two groups appeared, but a large overlap persisted. Blood dU‐test results tend to be higher in megaloblastic patients, but acquired folate deficiency obscures the distinction from normoblastic patients so that the test is not of diagnostic value.
Gene probe analysis demonstrates independent clonal evolution of co‐existent chronic myeloid and chronic lymphocytic leukaemia
Authors: Browett P. J. , Pattinson J. , Pinkney J. , Hoffbrand A. V. , Norton J. D.
Published: July 2010

We describe a case of Philadelphia‐positive chronic myeloid leukaemia occurring simultaneously with B‐cell chronic lymphocytic leukaemia in a 69‐yr‐old male. Gene probe analysis of DNA from both peripheral blood and bone marrow provided evidence for the independent evolution of 2 clones in this case, with a predominant population showing immunoglobulin heavy chain gene rearrangement and a smaller population showing a rearrangement within the breakpoint cluster region of chromosome 22.
Regression of intracerebral lesions in T prolymphocytic leukaemia treated with intravenous deoxycoformycin
Authors: Brito‐Babapulle Finella , Huang David , Lavender Peter , Galton David , Catovsky Daniel
Published: July 2010

A case of T‐prolymphocytic leukaemia (T‐PLL) presenting with deafness and confusion is reported. Computerised tomography (CT) of the head showed several well‐defined, rounded, high attenuation areas in the temporal, parietal and occipital regions of the brain substance that were suggestive of metastases. Treatment with weekly intravenous deoxycoformycin produced complete resolution of the CT abnormalities together with haematological evidence of disease regression 6 weeks after treatment was started.
Partial duplication of chromosome 1q preceding the development of an L3 lymphoblastic leukemia with t(8;14), secondary to treatment for Hodgkin's disease
Authors: Zollino M. , Genuardi M. , De Santis R. , Leone G. , Marra R. , Mancini R. , Mango G. , Neri G.
Published: July 2010

We report on a case of secondary lymphoblastic leukemia L3 in a patient treated with chemo‐ radiotherapy for a previous Hodgkin's disease. The typical chromosome translocation t(8;14) was found in association with a translocation t(9;19) and a marker chromosome 1, dup(1q). The same marker chromosome had been detected in a few cells of peripheral blood 2 years before the onset of the acute leukemia and may represent a proliferation‐associated change, responsible for the initiation of the process of leukemogenesis.
Results of induction and consolidation treatment with intermediate and high‐dose cytosine arabinoside and m‐Amsa of patients with poor‐risk acute myelogeneous leukaemia
Authors: Peters W. G. , Willemze R. , Colly L. P.
Published: July 2010

50 patients (aged 18–58 years) with acute myelogenous leukaemia after a preleukaemic phase (n = 14), acute myelogenous leukaemia that previously failed to respond to conventional chemotherapy (n = 9) or relapsed disease (n = 27) were given remission induction therapy consisting of cytosine arabinoside (1 g/m2 q 12 h × 12) and m‐Amsa (115 mg/m2 for 1 or 3 days). Overall, 27 patients (54%) achieved complete remission. The complete remission rate for patients with acute myelogenous leukaemia after a preleukaemic phase (7/14) and those with primary refractory or relapsed leukaemia (20/36) seems superior to that obtained with conventional remission‐induction therapy. 12 patients received 1–3 courses of consolidation chemotherapy with cytosine arabinoside (3 g/m2 q 12 h × 8) and m‐Amsa (115 mg/m2 for 1 d). 3 of them subsequently underwent autologous bone marrow transplantation. The median duration of remission for the remaining 9 patients was 8 months. 11 patients did not receive consolidation therapy; their median duration of remission was 3 months. The difference between the two groups was not significant. 4 patients underwent allogeneic bone marrow transplantation after achievement of complete remission. The impact of high‐dose cytosine arabinoside consolidation chemotherapy on poor‐risk acute myelogenous leukaemia remains unclear.
Biochemical and in vivo properties of commercial virus‐inactivated factor VIII concentrates
Authors: Berntorp Erik , Nilsson Inga Marie
Published: July 2010

The following commercial virus‐inactivated factor VIII concentrates were studied in vitro: AHF‐Kabi and Octonativ, KabiVitrum; Hemofil T, Hyland; Factorate HP and Monoclate, Armour; Nordiocto, Nordisk Gentofte (dry heated); Kryobulin TIM3, Immuno (steam treated); Profilate, Alpha (heated as dry material slammed in heptane); Hemate P, Behring (wet heated) and Octa‐V.I., Octapharma (solvent/detergent treated). The concentration of VIII:C was lowest in AHF‐Kabi, whereas it ranged from 24 to 53 IU/ml in the high purity concentrates, except for Monoclate in which it ranged from 91–128 IU/ml. All concentrates but Octa‐V.I. had higher values for VIILAg than for VIII:C. von Willebrand factor with normal distribution of multimers could only be demonstrated in AHF‐Kabi and Hemate P. In vivo studies were performed in 12 severe hemophiliacs. Recovery and half‐life of VIILC did not differ between the various concentrates. Hemate P was given to 5 patients with severe von Willebrand's disease, in all of whom a correction of the hemostatic defect was seen.
Hydrocortisone modulates colony‐stimulating activity produced by human bone marrow‐derived adherent cells
Authors: Hirata Jouji , Kaneko Shushi , Nishimura Junji , Motomura Seiji , Ibayashi Hiroshi
Published: July 2010

In an attempt to clarify the significance of hydrocortisone (HC) in human long‐term bone marrow cultures, the production of colony‐stimulating activity (CSA) and colony‐enhancing activity (CEA) by human bone marrow‐derived adherent cells (MDAC) and the modulation by HC were examined. The CSA production by MDAC was demonstrated using bilayer agar cultures. After treatment of MDAC with 10−6 mol/l HC, the CSA production was markedly enhanced, and after treatment of macrophages with 10−6 mol/l HC, the CSA production was inhibited. When added to a granulocyte‐macrophage precursor cells (CFU‐GM) assay system, HC inhibited colony formation. These results suggest that HC treatment directly stimulates CSA production by non‐macrophage cells of MDAC. The conditioned medium of the confluent layer of MDAC contained CEA, which was not influenced by the HC treatment of MDAC. Thus, HC plays an essential role in granulopoiesis in vitro, enhancing the CSA production by MDAC and inhibiting the differentiation of CFU‐GM.
Experimental basis of standardized specimen collection: Effect of posture on blood picture
Authors: Leppänen E. A. , Gräsbeck R.
Published: July 2010

22 subjectively healthy females were supine, sat in an armchair and stood while specimens of peripheral venous blood were collected after at least 15 min in each position without using a tourniquet. The albumin, haemoglobin, erythrocyte concentration and the haematocrit increased significantly when the subjects assumed a more erect position, probably as a result of increased hydrostatic pressure. The leucocyte count did not rise, and there was a statistically significant drop in the lymphocyte concentration when changing from supine to sitting. However, the leucocyte concentration rose significantly when the subjects stood up from supine or sitting, and the platelets increased significantly from supine to sitting or standing. When interpreting laboratory data, the difference in the behaviour of different cell species should be kept in mind. However, on the whole this study supports the stipulation contained in international recommendations that the posture of the subject should be standardized before collection of peripheral blood for haematological tests.
Comparison of acidified glycerol lysis test, Pink test and osmotic fragility test in hereditary spherocytosis: Effect of incubation
Authors: Bucx M. J. L. , Breed W. P. M. , Hoffmann J. J. M. L.
Published: July 2010

In this study we compared the results of the acidified glycerol lysis test, the Pink test and the osmotic fragility test in 38 patients with hereditary spherocytosis and in healthy controls. The sensitivity of the acidified glycerol lysis test was 81.6% when performed within 3 h after blood collection. After incubating for 24 h, the sensitivity increased to 100% whereas the specificity remained maximal. Similar incubation did not improve the diagnostic utility of the Pink test. All patients, but none of the controls, showed a positive osmotic fragility test. It is concluded, because of sensitivity and specificity in this study, that the acidified glycerol lysis test after incubation and the osmotic fragility test are superior to the Pink test in detecting spherocytosis.
Effects of triflusal and acetylsalicylic acid on platelet aggregation in whole blood of diabetic patients
Authors: De La Cruz J. P. , Pavia J. , Garcia‐Arnes J. , De La Cuesta F. Sanchez
Published: July 2010

A study was made on the inhibitory effect of triflusal (600 mg/d × 15) and acetylsalicylic acid (ASA, 400 mg/d × 15) on platelet aggregation in whole blood (WB) and platelet‐rich plasma (PRP) induced by ADP (2.5 μmol/l), adrenaline (50 μmol/l), collagen (1 μg/ml) and arachidonic acid (0.8 mmol/l), in 30 insulin‐dependent diabetic patients without vascular complications. Determination was also made of the serum levels of thromboxane B2 (TxB2) and of the plasma levels of 6‐keto‐PGF1‐alpha and of β‐thromboglobulin (B‐TG). Both drugs exhibited higher inhibitory effects in WB than in PRP. In WB, a significant difference between triflusal and ASA was observed against ADP‐induced aggregation (67% and 46% inhibition respectively, p < 0.01). Both drugs strongly inhibit the formation of TxB2 in serum (85% and 99%, respectively). Triflusal does not significantly change the plasma levels of 6‐keto‐PGF1‐alpha; ASA, by contrast, causes reduction of over 95% in those plasma levels. The plasma levels of B‐TG were not modified by either of the drugs.
Role of pokeweed mitogen spleen conditioned medium in regulating haematopoiesis in long‐term human marrow cultures*
Authors: Williams Zippora , Fabian Ina
Published: July 2010

The modulatory effect of pokeweed mitogen spleen conditioned medium (PWM‐SCM) on the growth of myeloid progenitors (CFU‐C) and on the composition of the stromal layer in human bone marrow long‐term cultures was studied. In the presence of PWM‐SCM there was enhanced CFU‐C growth in the adherent layer throughout 6 weeks of incubation, with 2‐fold, 2‐fold and 3.4‐fold increases during wk 2, 4 and 6 respectively (p < 0.05). In the non‐adherent layer of control cultures, however, there was a rapid decline in haematopoiesis which could not be offset by PWM‐SCM. The differentiation pattern of CFU‐C (entailing monocyte — macrophage progenitors CFU‐M, granulocytic progenitors CFU‐G or monocyte — granulocyte progenitors CFU‐GM) was not altered by PWM‐SCM. Fewer lipid‐containing cells developed in the adherent layer of cultures treated with PWM‐SCM than in control cultures, but the distribution pattern of monocytes — macrophages or granulocytes was not affected. These results suggest that in long‐term cultures of human marrow cells there may be extensive haematopoiesis in the presence of PWM‐SCM. Whether this is a direct effect on progenitor cells of stimulating factors, or rather of accessory cells in the adherent layer, remains to be clarified.
Diagnosis of meningeal involvement in childhood acute lymphoblastic leukemia: Cytomorphology and TdT
Authors: van Wering Elisabeth R. ,   (A study of the Dutch Childhood Leukemia Study Group), Veerman Anjo J. P. , van der Linden‐Schrever Birgit E. M.
Published: July 2010

Between December, 1984, and May, 1986, 98 CSF samples were sent to a central laboratory by postal express. The samples could be kept in a medium for up to 24 hours after the lumbar puncture. The quality of the cells proved to be good. Excluded were 5 samples delayed in delivery and 13 samples contaminated with blood, defined as the macroscopical presence of blood. The microscopical presence of erythrocytes in the cytocentrifuge preparation can make interpretation of the results difficult. Especially when leukemic blasts are present in the blood, extreme caution is necessary. A total of 71 samples could be studied by cytomorphology as well as by TdT‐IF. When cytomorphological leukemic blasts were present, this was confirmed by TdT‐IF positivity in all cases. But in 6 of 71 samples, TdT‐IF was positive without the presence of cytomorphological leukemic blasts. Follow‐up of these patients will show whether the therapeutic regimen has to be changed.
Erythroid colony formation by human CFU‐E is stimulated by compatible human serum but impaired by blood group antibodies
Authors: Arnaud Sylvie , Mouchiroud Guy , Blanchet Jean Paul
Published: July 2010

Normal human serum was shown to stimulate the proliferation of human CFU‐E when added into in vitro cultures of bone marrow cells. However, this was observed only when donors of serum and bone marrow cells were compatible on the basis of their blood groups. Absorption of incompatible sera removed the inhibition. Monoclonal anti‐blood group antibodies exhibited the same pattern of CFU‐E inhibition. The inhibition was complement‐independent. Using suspension bone marrow cultures, it was shown that this blockage took place at an earlier differentiation step than the CFU‐E level. This effect should be taken into account in studies of the inhibiting activities present in human anaemic sera.
In vitro platelet adhesion to vascular subendothelium: Studies in patients with polycythaemia vera
Authors: Lauri D. , Dejana E. , Cortelazzo S. , Orlando E. , Zanetti A. , Viero P. , de Gaetano G. , Barbui T.
Published: July 2010

In this work we studied platelet adhesion to subendothelial surfaces in 10 patients with polycythaemia vera and 10 healthy volunteers at 40% Hct (corresponding to the mean value of our control group) and 55% Hct (a value roughly corresponding to the mean Hct in polycythaemic patients). Platelet concentration was kept constant at 2.0–2.5 × 1011/l. The results indicate that there was a statistically significant increase in adhesion both in controls and in patients with Hct varying from 40% to 55%. The contribution of the higher Hct in promoting platelet adhesion was comparable in the two groups. When red blood cells (RBC) from the patients were tested with platelets from healthy volunteers in cross‐over experiments, they promoted adhesion in the same way as control RBC. Similarly, when patients' platelets were mixed with control RBC, adhesion was the same as control platelets. These data indicate that platelet and RBC contribution to this parameter are not significantly modified in this group of polycythaemic patients, provided that platelet and RBC values are adjusted to control range.
Platelet function in myeloproliferative disorders: Characterization and sequential studies show multiple platelet abnormalities, and change with time
Authors: Baker R. I. , Manoharan A.
Published: July 2010

Bleeding and thrombosis are well known major causes of morbidity and mortality in patients with myeloproliferative disorders (MPD) but the relationship between these clinical events and the commonly found platelet function abnormalities have not been established. In this study we performed simultaneous laboratory evaluations in 54 patients with MPD to investigate abnormalities in platelet aggregation and cyclooxygenase activity, the latter by using an in vitro aspirin inhibition test; the studies were repeated in 22 patients 1–27 months later. We have found platelet hyper‐ and hypofunction co‐existing in some patients (9/54), and change of platelet function during the course of the disease (7/22) with platelet hypofunction being the only constant abnormality over time. These results may explain the lack of correlation between the clinical events and the limited assessment of platelet function in the hitherto published studies, and also suggest the need for repeated evaluations to properly assess the relative risk for bleeding and thrombosis.
Effects of verapamil on uptake and in vitro toxicity of anthracyclines in human leukemic blastcells
Authors: Tidefelt U. , Sundman‐Engberg B. , Paul C.
Published: July 2010

The effect of a calcium channel blocker, verapamil, on intracellular uptake and cytotoxicity of anthracyclines in vitro was studied on leukemic cells from 32 patients with acute non‐lymphoblastic leukemia. Cells were isolated from peripheral blood or bone‐marrow and incubated with a concentration of 0.2 μmol/l, 0.5 μmol/l and/or 1.0 μmol/l of doxorubicin or daunorubicin in the absence and presence of verapamil at a concentration of 2 μmol/l and/or 10 μmol/l. Intracellular uptake was determined at the end of the incubations by photofluorometer and the in vitro cytotoxicity was determined after 5 days culturing in liquid medium by dye exclusion according to Weisenthal. Verapamil significantly increased the intracellular uptake of anthracyclines 0.5 μmol/l and 1.0 μmol/l and the cytotoxic effect of anthracyclines 0.2 μmol/l and 0.5 μmol/l and affected doxorubicin and daunorubicin equally. There were no significant differences between the two concentrations of verapamil. Cells from different FAB‐groups were equally affected by verapamil. The effect on intracellular uptake was higher in cells from patients who were resistant to therapy compared to those who achieved a complete remission. We conclude that verapamil has an effect on intracellular uptake and cytotoxicity of anthracyclines on tumor cells from patients with acute non‐lymphoblastic leukemia. The prognostic and therapeutic relevance of this has to be further evaluated.
Hodgkin's disease stages I and II with infradiaphragmatic presentation: A rare and prognostically unfavourable combination*
Authors: Specht L. , Nissen N. I.
Published: July 2010

Out of 323 patients with Hodgkin's disease CS I or II treated during the period 1969 to 1983 at Denmark's Finsen Institute, 35 presented with infradiaphragmatic disease. Patients with infradiaphragmatic presentation were older than patients with supradiaphragmatic presentation and were more often in stage II as opposed to stage I. NS histology was less prevalent among infradiaphragmatic than among supradiaphragmatic patients. Disease‐free survival and overall survival was poorer in infradiaphragmatic patients. When other factors of prognostic importance were taken into account in a multivariate analysis, infradiaphragmatic presentation turned out to be an adverse prognostic factor with regard to disease‐free survival, whereas it was not of significant independent prognostic value with regard to overall survival. Staging laparotomy in 11/35 infradiaphragmatic patients revealed 1 stage‐IV case. The 34 remaining early stage patients were treated by irradiation plus combination chemotherapy (21 patients), irradiation only (9 patients), or combination chemotherapy only (4 patients). They were followed until death or from 4 to 171 months after initiation of therapy. With regard to disease‐free survival, combined modality treatment (as opposed to radiotherapy only) was found to be of prognostic significance.
Leukaemoid reaction with megakaryocytic features in newborns with Down's syndrome
Authors: Cantù‐Rajnoldi A. , Cattoretti G. , Caccamo M. L. , Biasini A. , Bagnato L. , Schirò R. , Polli N.
Published: July 2010

A leukaemoid reaction was observed in 3 newborns with Down's syndrome. Thrombocytopenia was present in 2, requiring platelets transfusions in 1, and red cell transfusions were necessary in 2 patients. Blast cells characterization by specific monoclonal antibodies showed a prevalence of megakaryoblasts in all 3 cases. This feature was confirmed in 2 of them by the demonstration of platelet peroxidase (PPO) activity under transmission electron microscopy (TEM). A spontaneous remission of the leukaemoid picture was observed after 2–3 months. However, in 1 case a relapse of the myeloproliferative disorder with the same features of the blast cell population was diagnosed after 16 months. Chemotherapy with low‐dose Ara‐C, started because of a relevant clinical involvement, induced a complete remission.
Haplotypes of thalassaemic families from the Po river delta: Importance for prenatal diagnosis of β‐thalassaemia
Authors: Toffoli C. , Venturoli A. , Bardi A. , Lucci M. , Vullo C.
Published: July 2010

The β globin haplotypes, corresponding to 50 normal and 50 thalassaemic chromosomes, were determined in 25 families from the Po river delta area who had β thalassaemia. The haplotypes were obtained by studying the familial segregation of 6 restriction fragment length polymorphisms of the β globin gene cluster. The results show an almost exclusive presence of 3 haplotypes linked to the β thalassaemia chromosomes of this area: haplotype I, II and IX according to Orkin's classification. It is therefore possible that only two thalassaemic mutations are present. A wider variety of haplotypes was found to be linked to normal chromosomes. Prenatal diagnosis, by the analysis of polymorphic sites (the 6 plus one other) was possible in 92% of the cases. The probable high homogeneity of the molecular mutations makes the use of specific oligonucleotides practical and applicable to prenatal diagnosis.
Y‐body study in bone marrow precursors, peripheral blood cells and alveolar macrophages for demonstration of haemopoietic engraftment in allogeneic bone marrow transplantation
Authors: Ribera Josep‐Maria , Feliu Evarist , Rozman Ciril , Grañena Albert , Xaubet Antoni , Vives‐Corrons Joan‐Lluis , Ballesta Franclsca
Published: July 2010

The value of Y‐body study for assessment of haemopoietic engraftment was analyzed in 50 consecutive patients submitted to allogeneic bone marrow transplantation (BMT) (sex‐matched in 28 cases, sex‐mismatched in 22). The study was performed weekly on bone marrow and peripheral blood smears in all cases, and alveolar macrophages were also studied in 15 patients in whom bronchoalveolar lavage was carried out because of concurrent respiratory disturbances. The analysis was performed blindly by 2 independent observers. In both sex‐matched and sex‐mismatched cases there was an absolute concordance between recipient and donor Y‐body results, as well as with the simultaneous cytogenetic study. The engraftment of erythroid and granulopoietic lines was documented at day +14 in all cases of sex‐mismatched BMT, whereas megakaryocyte and lymphocyte take was demonstrated at d +21. On the other hand, the results from alveolar macrophages were in accordance with those obtained in the simultaneous study of bone marrow precursors after BMT. The above results indicate that Y‐body analysis is a simple and useful tool for the demonstration of bone marrow take in sex‐mismatched BMT.
Repair of UV‐induced DNA damage in aplastic anaemia: Changes after treatment with antilymphocyte globulin (ALG)
Authors: Kovacs E. , Nissen C. , Speck B. , Signer E.
Published: July 2010

The extent of DNA‐repair induced by UV‐C irradiation was measured in peripheral unstimulated lymphocytes of 24 patients with aplastic anaemia at different stages of disease and compared with the results obtained in 92 controls. As parameter of the DNA‐repair synthesis, the incorporation of (3H)thymidine in the presence of 2 mmol/l hydroxyurea (HU) was taken. Of 19 patients tested after treatment with antilymphocyte globulin (ALG), 5 were in complete autologous haemopoietic remission, defined as > 1000 granulocytes/mm3 > 100000 platelets/mm3 and a nontransfused haemoglobin value > 10 g%. 14 patients were in partial remission, defined as improvement of haemopoietic function, not meeting the criteria for complete remission. 4/5 patients in complete remission had normal DNA‐repair synthesis, compared to 4/14 patients in partial remission. In 92 controls, a normal level was found in 70 cases. In 4/5 patients examined at diagnosis and at various intervals after ALG‐treatment, DNA‐repair synthesis was low at diagnosis. It increased after therapy and paralleled improvement of haemopoietic function to some extent. It is suggested that in aplastic anaemia there are different populations of lymphocytes with differing DNA‐repair capacity; ALG treatment seems to favour expansion of the normal population, which is associated with improvement of haemopoietic function.
Idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia in Hodgkin's disease
Authors: Xiros N. , Binder T. , Anger B. , Böhlke J. , Heimpel H.
Published: July 2010

Idiopathic thrombocytopenic purpura (ITP) and Coombs' positive hemolytic anemia (AIHA) were found, respectively, in 5 (1%) and 1 (0.2%) of 492 patients with Hodgkin's disease (HD). 33 cases of ITP associated with HD reported in the literature are reviewed. Of our cases, ITP was coincident with the diagnosis of HD in 1 patient. In another patient ITP preceded the diagnosis of HD by 41 months and in the remaining 3 patients the diagnosis of ITP was established after they had been successfully treated for HD. A herpes zoster infection preceded ITP by 1 month in 1 patient and another had herpes zoster at the time of diagnosis of ITP. AIHA had preceded the diagnosis of HD by 8 months in 1 case. In patients with ITP the prognosis seems to be related only to the status of the underlying HD.
Calcitonin‐related peptides in patients with acute leukemia: Association of human calcitonin with poor prognosis
Authors: Pflüger Karl‐Heinz , Koeppler Hubert , Havemann Klaus , Holle Rolf
Published: July 2010

Elevated serum levels of peptides hormones in patients with acute leukemia and production of these agents by the leukemic blasts have been described. In 77 patients with acute leukemia the influence of common risk factors and elevations of serum levels of calcitonin‐related peptides on clinical outcome was evaluated. By multivariate analysis, only age and elevated serum level of h‐CT were found to be significantly correlated to survival. CGRP and s‐CT showed no influence on outcome. Closer inspection of the clinical course of these patients showed that patients with elevated h‐CT are not likely to survive the first 4 weeks after diagnosis. The possibility that this hormone may influence the biological behavior of the leukemic cells is discussed.
Therapeutic effects of low‐dose cytosine arabinoside, alpha‐interferon, 1α‐hydroxyvitamin D3 and retinoic acid in acute leukemia and myelodysplastic syndromes
Authors: Hellström E. , Robèrt K‐H , Gahrton G. , Mellstedt H. , Lindemalm C. , Einhorn S. , Björkholm M. , Grimfors G. , Udén A‐M , Samuelsson J. , Öst A. , Killander A. , Nilsson B. , Winqvist I. , Olsson I.
Published: July 2010

62 evaluable patients with myelodysplastic syndromes (MDS) or acute leukemia were treated with different combinations of low dose ara‐C, α‐interferon (IFN), 1α‐hydroxyvitamin D3 (vit D3) and retinoic acid. The aim was to study the efficacy and toxicity of each combination. The overall rate was 44%. Of these, 50% responded favorably to the combination of IFN, vit D3 and retinoic acid (IDR), which was comparable to the response rate of 43% for low‐dose ara‐C. The results of the IDR treatment may be explained by additive or synergistic effects between the separate drugs in the combination. Ara‐C and IDR treatment was generally well‐tolerated but interferon gave more side effects than any other drug used in the study. Evaluation of the full combination of ara‐C, IFN, vit D3 and retinoic acid was not possible because of toxicity. Marrow hypoplasia was infrequent (5/27 patients) in cases responding favorably to treatment. Complete remissions were not longer than partial remissions or significant responses.
Assessment of splenic and RES function of patients with thalassemia major long after partial splenic embolization: In vivo clearance study
Authors: Germenis A. , Antipas S. E. , Dimitriou P. , Politis C. , Spigos D.
Published: July 2010

The activity of the remaining reticuloendothelial system (RES) and the function of the splenic remnants was estimated in 5 thalassemic patients who had undergone successful partial splenic embolization (PSE) 6 yr previously. The kinetics of 125I‐heat‐denatured human albumin as well as that of 51Cr‐heat‐damaged homologous red blood cells were applied for this purpose and the parameters derived were compared to those of nonsplenectomized as well as splenectomized thalassemics with the following results: (a) The parameters of splenic function in embolized thalassemics were found to be within the limits observed in nonsplenectomized patients. (b) Their maximum phagocytic capacity was significantly lower, not only than that found in nonsplenectomized, but also than in thalassemic patients splenectomized at about the same time. It is concluded that, 6 yr after PSE has been performed, a reorientation of the altered circulatory dynamics has taken place in the splenic remnants allowing previously blockaded areas to gain normal function. It therefore seems that, despite the continuing hemolytic stimulus, RES hyperplasia is prevented, resulting in the stable, low‐level transfusion requirements that have been observed in embolized thalassemics.
Isolated gingival relapse in acute myeloid leukaemia
Authors: Bergmann O. J. , Philipsen H. P. , Ellegaard J.
Published: July 2010

A 47‐yr‐old man with acute myeloid leukaemia had been in complete remission for 18 months when he developed a gingival tumour. Histological examination revealed leukaemic infiltrate and, at this stage, no other signs of relapse could be demonstrated. Chemotherapy and local radiotherapy resulted in the disappearance of the mass; however, histological abnormalities persisted. First relapse of acute myeloid leukaemia presenting as a gingival tumour has not been previously reported.
Critical value of laparotomy with splenectomy in Stage III Hodgkin's disease as restaging procedure after chemotherapy
Authors: Mazza P. , Poletti G. , Zinzani P. L. , Gherlinzoni F. , Miniaci G. , Tonielli E. , Sciascia R. , Tura S.
Published: July 2010

38 patients with stage III Hodgkin’ disease underwent laparotomy with splenectomy as restaging procedure after first line chemotherapy which included MOPP, ABVD, or both. 28 patients were judged to be in clinical complete remission (CR) and 10 were resistant or had relapsed. Among patients in CR, 27 (96%) were confirmed to be in pathological CR; among patients resistant or relapsed, 9 (90%) were confirmed to have disease in the abdomen or retroperitoneum. The therapy for patients in clinical remission before laparotomy consisted of TNI or sTNI in 19 patients, mediastinal radiation in 6 patients and no further therapy in the remaining 3 patients. No significant differences were seen in survival and relapse‐free survival between those patients treated by extensive and those treated by local radiotherapy or no further therapy. Instead, among those patients who received extensive radiotherapy 3 developed acute non‐lymphoid leukemia (ANLL). The therapy for this group of patients consisted of further chemotherapy in 7 who had concomitant liver involvement and TNI in the remaining 3 who had the disease confined to the spleen and/or lymph nodes. Among these patients, only 3 obtained CR; 2 with radiation and 1 who was resistant to MOPP, with ABVD. This study leads us to re‐consider the role of laparotomy in stage III HD which should be used as non‐routine procedure only in selected patients without poor prognostic factors who may be cured by radiotherapy alone. In patients resistant to chemotherapy, an early evaluation of disease in the abdomen may be useful for a better salvage treatment.
Significance of granulomas in bone marrow: A study of 40 cases
Authors: Vilalta‐Castel E. , Valdés‐Sanchez M. D. , Guerra‐Vales J. M. , Teno‐Esteban C. , Garzón A. , López J. I. , Ricard M. P. , Abarca M. , Garcia‐Diaz Juan de D.
Published: July 2010

Granulomas in bone marrow are an infrequent finding related to diverse disease. We reviewed 8057 bone marrow studies made over a period of 10.5 years, confirming the presence of granulomas in 40 patients. Global incidence was 0.50% and annual incidence 3.80 cases/yr. Because of the non‐specificity of the morphological data, the diagnostic significance of the finding is limited, but it does serve to narrow the field of etiological possibilities. Associated disease was demonstrated in 82.5%, infectious diseases being the most common (tuberculosis, brucellosis, typhoid fever and kalaazar). Two previously unpublished entities are introduced: refractory anemia with excess blast cells (dysmyelopoietic syndrome) and malignant histiocytosis. 3 patients presented human immunodeficiency virus infection, the etiopathogenic role of this retrovirus in the generation of granulomas being unknown. The efficacy of bone marrow study in demonstrating granulomas increases if both the aspirate clot and bone cylinder are examined.
A study of immunogold‐labelled blood group A erythrocytes in the scanning electron microscope
Authors: Heier H. E. , Namork E. , Falleth E.
Published: July 2010

This report presents binding patterns on A1, A2, A3, Ax and Ae1 erythrocytes of a monoclonal anti‐A (A 003) antibody which reacts predominantly with difucosylated A oligosacccharides, visualized with colloidal gold particles in the backscattered electron imaging mode of a scanning electron microscope. A relatively weak labelling was found on most A, cells, while the labelling in subgroups A2, A3 and especially Ax appeared relatively stronger. Very few Ae1 cells were labelled. The results emphasize the qualitative uniqueness of A1 and suggest that many Ax cells have high proportions of difucosylated A oligosaccharides. Labelling variations were found between different A3 and Ax traits, and in all subgroups between cells and even between different parts of the cells. No immunolabelling differences were found in relation to secretor status.
Streptokinase and reduced plasma viscosity: A second benefit
Authors: Moriarty A. J. , Hughes R. , Nelson S. D. , Balnave K.
Published: July 2010

The purpose of this pilot study on a small cohort of patients (n = 13) with acute myocardial infarction receiving systemic streptokinase (STK) thrombolytic therapy was to measure the decrease in plasma viscosity concomitant with fibrinogen depletion. The treatment group was compared with a similar control group not given thrombolytic therapy. Serial relevant blood studies were undertaken in both groups for a period of 6 d. In the treatment group, a maximum reduction in plasma viscosity of 17 ± 9% (mean ± S.D.) was achieved during the first 24 h. Plasma viscosity remained below baseline for the 6‐d duration of the study. Conversely, in the control group, the plasma viscosity rose to a maximum of 19 ± 14% (mean ± S.D.) over the period of study, parallelling the rise in plasma fibrinogen as an acute‐phase reactant. Correlation studies between viscosity and plasma fibrinogen were strongly positive with mean values of r of 0.74 and 0.66 in the STK‐treated group and controls, respectively. We conclude that the benefit of systemic STK treatment may in part be due to reduced myocardial workload and oxygen consumption at a critical time, and improved microvascular circulation, consequent on reduced plasma viscosity.
Multiple myeloma in central and northern Norway 1981–1982: A follow‐up study of a randomized clinical trial of 5‐drug combination therapy versus standard therapy
Authors: Kildahl‐Andersen O. , Bjark P. , Bondevik A. , Bull O. , Burgess G. , Dehli O. , Hoel S. , Jæger S. , Kvambe V. , Mürer F. , Nordahl E. , Ræder S. , Seip T. , Wilskow A. , Ytrehus K. , Grøttum K. , Lamvik J.
Published: July 2010

In a randomized study of 92 previously untreated patients with multiple myeloma, the intention was to document the possible beneficial effect of combination chemotherapy including vincristine, carmustine, alkylating agents and prednisone, as compared to conventional therapy with melphalan and prednisone. Major prognostic factors did not differ significantly between the treatment groups. With the 2‐drug therapy and 5‐drug combination therapy, 48 and 54% of the patients achieved remission, respectively. Median survival for patients treated with the 2‐drug regimen and 5‐drug regimen was 29 and 33.5 months, respectively. No significant difference was found between the survival curves for stage III patients treated with the two regimens. After 12 months, patients who had achieved remission were randomized to have treatment discontinued or to have maintenance treatment. The numbers of relapses, remission duration and survival of the two groups were similar.
Lactoferrin‐mediated transfer of iron to intracellular ferritin in human monocytes
Authors: Birgens H. S. , Kristensen L. Østergaard , Borregaard N. , Karle H. , Hansen N. E.
Published: July 2010

Interactions of 125I‐59Fe‐lactoferrin with human monocytes were studied. After 4 hours of incubation, the uptake of 59Fe exceeded that of 125I. In dissociation studies the cellular 59Fe‐activity was only partly dissociable during 16 h, whereas the 125I‐activity could be released nearly completely. Disruption of the cells and studies on the cytosolic phase were performed employing gel‐filtration and affinity chromatography. An appreciable amount of lactoferrin was found in the cytosolic phase. About 50% of the cytosolic 59Fe‐activity was bound to ferritin. The results suggest that lactoferrin is internalized into monocytes and that iron is transferred to ferritin. These cellular events may contribute to an understanding of the accumulation of iron in the monocyte/macrophage system observed during inflammatory conditions.
Investigation of nuclear clefts as a prognostic parameter in chronic lymphocytic leukemia
Authors: Molica Stefano , Alberti Antonio
Published: July 2010

The importance of cell morphology with respect to the presence or absence of nuclear clefts (NC) in peripheral blood lymphocytes has been investigated in 86 previously untreated chronic lymphocytic leukemia (CLL) patients. Cleaved cells were considered to be present in significant numbers when they exceeded 5% of the peripheral blood lymphocytes. On this basis patients could be divided into two morphological groups. Age, sex and distribution of stages, as well as mode of clinical presentation were alike in the two groups of patients. In contrast, lymph node involvement was more frequently encountered in patients with NC > 5% (p < 0.01). Both survival and treatment‐free period probabilities were not statistically correlated to the quantitative changes in the percent value of NC. We further confirm that Binet's clinical staging is a significant predictor of survival irrespective of NC.
Clonal analysis of the response of HL‐60 cells to retinoic acid and vitamin D in the presence or absence of leukocyte‐conditioned medium
Authors: Soppi Esa , Robért Karl‐Henrik , Gahrton Gösta
Published: July 2010

The capacity of retinoic acid (RA) and vitamin D to induce differentiation of HL‐60 cells in an agar gel system that permits a high cloning efficiency was studied in the presence or absence of leukocyte‐conditioned medium (LCM). Vitamin D was about 10 times more effective in inducing differentiation than RA. LCM significantly increased the differentiation‐inductive capacity of both vitamins, although LCM did not have an effect of its own. During the first days of culture, the number of cells per clone increased with either vitamin or LCM alone as compared to control cultures. This suggests that cellular proliferation may be important in the initial phase of the differentiation induction. No synergy in this respect was found between RA and vitamin D in the presence or absence of LCM. Thus it is doubtful whether RA and vitamin D have a true synergistic effect on individual HL‐60 cell differentiation as previously described in liquid cultures. Furthermore, the findings suggest that the process of differentiation induction regarding the growing cells in agar gel involves an all‐or‐none process. The data may also help elucide the observed relationship between the in vitro production of colony stimulating activity and favorable prognosis of AML.
Reticulocyte crisis after splenectomy: Evidence for delayed red cell maturation?
Authors: De Haan L. D. , Werre J. M. , Ruben A. M. Th. , Huls A. H. , de Gier J. , Staal G. E. J.
Published: July 2010

In whole blood from splenectomized subjects (n = 8) in a steady state an increased number of reticulocytes was observed (14.0 ± 7.8 ‰ versus 3.6 ± 2.4 ‰ controls: p < 0.05). Cell fractionation on density showed that reticulocytes, as in normals, are more or less confined to the least dense fraction; cell fractionation on volume revealed that reticulocytes form a heterogeneous cell population with diverging volume, but sharing a low density. Immediately after splenectomy (n = 4), a reticulocytosis is observed, mainly manifest in the top fractions (262.0 ± 49.0 ‰ versus 40.0 ± 32.4 ‰ preoperatively; p < 0.01). This reticulocytosis is not due to pre‐ or postoperative complications, but is associated with the splenectomy itself and probably is the consequence of a delayed, but ultimately occurring red cell maturation. The increase of reticulocytes is not accompanied by significant alterations in cell morphology, as far as cell volume is concerned.
Prognostic factors in Hodgkin's disease stage III with special reference to tumour burden
Authors: Specht Lena , Nissen Nis I.
Published: July 2010

143 patients with Hodgkin's disease stage III (65 PS III, 78 CS III) were treated with radiotherapy alone (33 patients), combination chemotherapy alone (56 patients), or radiotherapy plus combination chemotherapy (54 patients). They were followed till death or from 7 to 191 months. Prognostic factors including treatment, peripheral + intrathoracic tumour burden (assessed by combining tumour size in each involved region with number of involved regions), intraabdominal tumour burden (assessed by combining size of lymphographically involved lymph nodes in each region with number of lymphographically involved regions), histologic subtype, B‐symptoms, number of involved regions, mediastinal involvement, pretreatment ESR, sex, age, laparotomy, and substage were examined in multivariate analysis. With regard to disease‐free survival, total tumour burden (intraabdominal and peripheral + intrathoracic) emerged as the only pre‐treatment factor of independent prognostic significance. With regard to overall survival the only factor of independent significance apart from age turned out to be intraabdominal tumour burden. The results of the present study thus support recently published findings regarding early stage disease to the effect that tumour burden is the single most important prognostic factor in Hodgkin's disease.
Interaction between platelets and lupus anticoagulant
Authors: Galli Monica , Cortelazzo Sergio , Viero Piera , Finazzi Guido , de Gaetano Giovanni , Barbui Tiziano
Published: July 2010

10 consecutive patients fulfilled the diagnostic criteria for lupus anticoagulant. 4 had concomitant systemic lupus erythematosus, 1 Waldenstrom's disease and 5 had no apparent underlying disease. Only the case with Waldenstrom's disease presented a bleeding tendency, with bleeding time > 20 min; the others had a history of thrombotic complications. A defect of platelet aggregation induced by ADP, apinephrine, collagen and arachidonic acid was documented in the Waldenstrom's disease case whose lupus anticoagulant was an IgM. In the others, lupus anticoagulant, identified as IgG immunoglobulins, produced no aggregation abnormalities. However, beta‐thromboglobulin levels in platelets, plasma and urine were consistent with a pattern of platelet activation in all cases. IgG immunoglobulins separated from sera of 6 patients showed lupus anticoagulant activity, with no effects on platelet aggregation of normal platelet‐rich plasma, but they induced secretion of beta‐thromboglobulin from normal platelets.
Tetrahydrofolate dehydrogenase cytochemistry in acute lymphoblastic leukemia
Authors: Invernizzi R. , Nano R. , Perugini O. , De Fazio P. , Nespoli L. , Gerzeli G. , Ascari E.
Published: July 2010

We studied the cytochemical distribution of tetrahydrofolate dehydrogenase (FH4D), an enzyme involved in nucleic acid metabolism and thus in cell proliferation and differentiation processes, in bone marrow blasts from 37 cases of acute lymphoblastic leukemia (ALL), of whom 23 were pediatric patients. 26 cases were analyzed at onset, 11 in relapse. The ALL cases were immunologically classified as T (10), common (20), B (3) and null (4). In each subgroup the majority of lymphoblasts were positive, with heterogeneous positivity patterns and variable degrees of enzyme activity. Most T lymphoblasts were characterized by focal localization of FH4D, whereas in common blasts reactivity — usually less strong — was either focally localized or scattered with several fine granules. Finally, many B and null blasts showed diffuse positivity. A quantitative evaluation of FH4D activity using cytophotometric technique (Vickers M86) demonstrated higher degrees of reactivity in leukemic blasts than in normal lymphocytes. Moreover, slightly different levels of reactivity were observed in relation to immunological phenotype, age and stage of the disease. Therefore we think that FH4D is a useful additional marker for ALL characterization.