bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity in type IIB von Willebrand disease: Two unrelated cases with no family history and mild abnormalities of ristocetin‐induced interaction between von willebrand factor and platelets
Authors: Federici A. B. , Mannucci P. M. , Bader R. , Lombardi R. , Lattuada A.
Published: February 2007

Two patients from two separate families were diagnosed as having type IIB von Willebrand disease, because they had lifelong bleeding tendencies, prolonged bleeding times, no large von Willebrand factor multimers, and low levels of ristocetin cofactor in plasma with heightened ristocetin‐induced platelet aggregation. There was no history of bleeding, and no laboratory abnormalities were found in the parents and sibship of either propositi, in contrast with the autosomal dominant pattern of inheritance usually observed in type IIB von Willebrand disease. Abnormalities of ristocetin‐induced von Willebrand factor‐platelet interactions were less severe than in a patient from a previously reported family with type IIB von Willebrand disease studied in parallel. The peculiar features of these cases provide additional evidence of the existence of heterogeneity within this variant.
Hemostatic defects in response to aspirin challenge in hypothyroidism
Authors: Zeigler Zella R. , Hasiba Ute , Lewis Jessica H. , Vagnucci Anthony H. , West Valerie A. , Bezek Elizabeth A.
Published: February 2007

A patient with hypothyroidism had ingested aspirin and bled profusely following dental extraction. The only abnormalities noted on coagulation survey were a prolonged aspirin bleeding time and reduced retention of platelets on glass beads. Based on this index case, an additional 12 hypothyroid patients, on no medications, were evaluated for a mild bleeding disorder, including studies with aspirin challenge. The results indicate that thrombin‐induced platelet serotonin release, following aspirin ingestion, was subnormal in most hypothyroid patients. However, only hypothyroid individuals with TSH levels of > 60 μ U/ml have an increased hemostatic sensitivity to aspirin, as measured by the bleeding time test. These findings did not appear to result from decreased synthesis of the factor VIII‐von Willebrand factor complex. As this drug is commonly ingested, the effects of aspirin on bleeding may explain the easy bruising and menorrhagia that occur in hypothyroid individuals.
Effect of serum from patients with idiopathic thrombocytopenic purpura on cultured endothelial cell growth
Authors: Nakajima Tokuo , Kakishita Eizo , Nagai Kiyoyasu
Published: February 2007

This study examined the effects of platelet‐derived serum factors from patients with idiopathic thrombocytopenic purpura (ITP) on human umbilical cord vascular endothelial cell growth and DNA synthesis. Vascular endothelial cell growth factors were identified in the platelet extracts, and platelet‐derived vascular endothelial cell growth factors with molecular weights of less than 10,000 were also identified in the sera. These growth factors were stable even after 30 minutes of heat treatment at 56°C and acid treatment.

When ITP patient serum was added to vascular endothelial cells, their growth capacity and DNA synthesis capacity were lower than when serum from normal subjects or patients with ITP in remission was added. This indicated that in ITP, impairment of vascular integrity and abnormal repair of the vascular walls that accompany thrombocytopenia may be causes of the predisposition to hemorrhage. The decrease in ITP of platelet‐derived vascular endothelial cell growth factors with molecular weights of less than 10,000 was hypothesized to be a contributory factor.
DNA damage induced by chloramphenicol and its nitroso derivative: Damage in intact cells
Authors: Yunis A. A. , Arimura G. K. , Isildar M.
Published: February 2007

We have postulated that the p‐NO2 group of chloramphenicol (CAP) is the structural feature underlying aplastic anemia from this drug. In a series of studies to examine this hypothesis we have demonstrated the toxic nature of the CAP‐reduction intermediate nitroso CAP (NO‐CAP) and its damaging effect on isolated DNA in vitro. The present study was designed to examine the comparative effects of CAP, NO‐CAP, and thiamphenicol (TAP) on the integrity of DNA in intact cells. By using the alkaline elution technique of Kohn, DNA damage in the form of single strand breaks could be readily demonstrated in cultured Raji cells and in PHA‐stimulated normal human lymphocytes by small concentrations of NO‐CAP (0.05‐0.1 mM). A small but reproducible effect was observed from large concentrations of CAP (2 mM). In contrast, TAP, lacking the p‐NO2 group, was without effect.
Bone marrow transplantation in a patient with myelodysplasia associated with diffuse eosinophilic fasciitis
Authors: Tallman Martin S. , McGuffin Robert W. , Higano Celestia S. , Starkebaum Gordon , Collins Steven J. , Johnston Harold , Singer Jack W. , Perry David J. , Kunath Arthur
Published: February 2007

A 34‐year‐old man with diffuse eosinophilic fasciitis and a hypocellular myelodysplastic syndrome underwent marrow transplantation from an HLA‐identical brother. Prompt hematopoietic reconstitution was observed, strongly suggesting that the marrow hypocellularity was caused by neither a serum inhibitory factor nor a microenvironmental disorder. The patient died of disseminated cytomegalovirus infection too early to evaluate the impact of hematopoietic reconstitution on the eosinophilic fasciitis. Nevertheless, marrow transplantation may offer a therapeutic option for those patients with this disorder who develop severe hematopoietic dysfunction and who have a suitable marrow donor.
In vitro correlates of low dose Ara‐C efficacy: Clinical, cytogenetic, and bone marrow culture analysis
Authors: Weisdorf Daniel J. , Perri Robert T. , Oken Martin M. , Miller Wesley J. , Arthur Diane C. , Machnicki Joy L.
Published: February 2007

Low‐dose Ara‐C (10 mg/m2 subcutaneously bid) has been used as an alternative therapy for acute nonlymphocytic leukemia (ANLL) and myelodysplastic syndromes. We sought to define its therapeutic mechanism by assessing clinical and cytogenetic responses to treatment in conjunction with careful in vitro study of both morphologic and functional characteristics of bone marrow cells cultured with Ara‐C. Sixteen patients (12 ANLL, four myelodysplastic syndrome) were treated. All developed pancytopenia and 11 of 12 had bone marrow hypoplasia during treatment. Four had a meaningful clinical response while five more showed in vivo leukemic cell sensitivity to low‐dose Ara‐C. Seven showed no reponse. Cells with cytogenetic abnormalities were either decreased in number or eradicated during clinical improvement. Liquid culture of marrow mononuclear cells with Ara‐C (.033‐.333 μg/ml × 7 days) produced little evidence of morphologic or functional differentiation (ten of 11 studied). No functional maturation was observed in cells from clinically responding patients. We conclude that low‐dose Ara‐C is modestly effective for some patients with ANLL or myelodysplasia. However, no evidence for in vivo leukemic differentiation is suggested by either in vitro culture studies or cytogenetic correlates of clinical response. In vitro marrow culture studies failed to predict clinical response to Ara‐C.
Antithymocyte globulin therapy for pure white cell aplasia
Authors: Firkin F. C. , Prewett E. J. , Nicholls K. , Moran J.
Published: February 2007

Severe neutropenia due to selective loss from the bone marrow of cells of the entire neutrophil maturation sequence developed in a patient with Goodpasture's Syndrome and was associated with serious infections complicating continuous ambulatory peritoneal dialysis. Involvement of T‐lymphocytes in the process affecting the neutrophil series was implicated by the relation between recovery from neutropenia and treatment with antithymocyte globulin (ATG). Azathioprine and corticosteroid administration failed to sustain recovery from neutropenia induced by ATG. It is concluded that ATG can provide a nonmyelotoxic form of therapy for pure white cell aplasia whose effectiveness is independent of responsiveness to other immunosuppressive agents.
Porphyria cutanea tarda associated with the acquired immune deficiency syndrome
Authors: Wissel Paul S. , Sordillo Peter , Anderson Karl E. , Kappas Attallah , Sassa Shigeru , Savillo Robert L.
Published: February 2007

Three male subjects with cutaneous symptoms and biochemical signs typical of porphyria cutanea tarda (PCT) developed acquired immune deficiency syndrome (AIDS). All three were in a classic high risk group for the latter disease and developed a typical progressive illness. Two patients succumbed to opportunistic infections; the third is alive but critically ill. The symptomatic prodrome of AIDS developed concurrently with or followed the onset of symptoms of PCT in all three individuals. PCT and AIDS are both uncommon disorders; their association in three patients is thus of inherent clinical interest. If this association is not coincidental, it raises the possibility that the occurrence of photosensitivity, skin lesions, and evidence of biochemical changes characteristic of PCT may, in certain patients at risk for AIDS, presage the subsequent full clinical expression of the latter disease.
Platelet kinetics in human immunodeficiency virus induced thrombocytopenia
Authors: Bel‐Ali Zoher , Dufour Valérie , Najean Yves
Published: February 2007

A platelet kinetic study was performed in 34 patients (33 homosexuals and/or drug addicts) with (in most of them) severe and isolated thrombocytopenia and human immunodeficiency virus positive serological tests. The reported data indicate that the thrombocytopenia is due to an extracorpuscular hyperdestruction. The sequestration of the labeled platelets is exclusively splenic in most of the cases. Splenectomy was successful in the ten cases in which it was done; however, corticoids showed no or low effect, and Ig‐G infusion had only a temporary efficacy.
Pure red cell aplasia as possible early manifestation of chronic myeloid leukemia
Authors: Haas Oskar A. , Hinterberger Wolfgang , Mörz Reinhard
Published: February 2007

Cytogenetic studies as well as erythroid and myeloid progenitor cell assays were performed in a 29‐yr‐old epileptic man with pure red cell aplasia (PRCA) who had been treated with primidone for several years. Despite clinical evidence of preleukemia, our studies indicated an underlying atypical Philadelphia chromosome‐positive myeloproliferative disorder. These laboratory findings were confirmed by the subsequent development of chronic myeloid leukemia (CML) which terminated in a CALLA‐positive lymphoblastic crisis 32 months later.

The rare concurrent occurrence of PRCA and CML and the possible inducing role of the preceding antiepileptic treatment are discussed.
Clonal immunoglobulin gene rearrangements in chronic lymphocytic leukemia: A correlative study
Authors: Soper L. , Bernhardt B. , Eisenberg A. , Cacciapaglia B. , Bennett L. , Sanda A. , Baird M. , Silver R. , Benn P.
Published: February 2007

Forty‐two patients with chronic lymphocytic leukemia (CLL) were studied for immunoglobulin gene and T‐cell receptor gene rearrangements. Immunoglobulin heavy chain gene rearrangements were demonstrable in 41 cases. One rearrangement of the T‐cell receptor beta chain gene was detected. Quantification of the relative intensities of germline and rearranged DNA bands suggests that a significant component of the lymphocytosis may be due to cell populations other than the malignant clonal population, particularly in earlier stages of the disease. A direct relationship was found between severity of disease and the relative amount of clonal immunoglobulin heavy chain gene rearrangement. Preliminary data for 12 patients followed sequentially indicated that clinical deteriorations or improvements are reflected in an increase or decrease, respectively, in the proportion of cells with rearranged immunoglobulin genes.

Change in the relative proportion of cells with germline versus rearranged genes may provide an additional useful criterion for staging CLL, for more precisely defining the abnormal lymphocyte population, and for monitoring progression of the disease and efficacy of treatment.
Serum‐free culture of human hemopoietic progenitors in attenuated culture media
Authors: Sonoda Yoshiaki , Ogawa Makio
Published: February 2007

To elucidate the precise mechanisms of molecular and cellular regulation of hemopoiesis, it is necessary to develop a chemically defined culture assay for purified hemopoietic progenitors. To approach this long‐term goal, we attempted to develop a serum‐free culture system for enriched human progenitors that permits expression of all hemopoietic lineages and stages of development. Preliminary studies indicated that α‐medium was superior to iscove's modified Dulbecco's medium (IMDM) and that culture under low (5%) oxygen condition was better than an ambient level of oxygen. We developed an attenuated (modified quarter‐strength) α‐medium and compared the colony‐supporting ability of the three media by plating 1,000 bone marrow null cells per dish in the presence of a combination of recombinant human colony‐stimulating factors (CSFs). The numbers of colonies supported in α‐medium and attenuated α‐medium were approximately 70% of those in serum‐containing cultures. IMDM failed to support colony formation. While, in general, the colony sizes were smaller in the serum‐free cultures than in the serum‐containing cultures, a variety of types of single lineage and multilineage colonies were seen in serum‐free culture. A linear relationship between cell number and colony formation was seen in 100‐2,000 cells per dish. Serum‐free cultures of enriched human progenitors should be an important tool for analysis of the mechanisms of recombinant CSFs.
Acute tumor lysis syndrome in non‐Hodgkin lymphoma induced by dexamethasone
Authors: Dhingra Kapil , Newcom Samuel R.
Published: February 2007

Acute tumor lysis syndrome developed in a 30‐year‐old man with non‐Hodgkin lymphoma after dexamethasone administration. To the best of our knowledge this case is the first one reported following single agent corticosteroid treatment.
Unique promotion of erythrophagocytosis by malondialdehyde
Authors: Hebbel Robert P. , Miller Wesley J.
Published: February 2007

Modification of the normal erythrocyte membrane by reagent malondialdehyde (MDA) promotes phagocytosis of red blood cells by human macrophages, a phenomenon previously shown to involve both IgG‐dependent and IgG‐independent mechanisms and to be demonstrable even at micromolar MDA concentrations. In the present studies, we demonstrate this effect using 1mM MDA prepared both by acid hydrolysis of malonaldehyde bis‐(dimethyl acetal) and by enzymatic synthesis from 1,3‐propanediol. Remarkably, we find that equimolar amounts of other mono‐ and dialdehydes fail to promote erythrophagocytosis despite similarity to MDA in size and structure and ability to cross link. Authentic MDA seems to be unique among small aldehydes in ability to promote erythrophagocytosis at low aldehyde concentration and, therefore, has a special biologic relevance among the great variety of peroxidation byproducts.
Testing for cell surface forms of class II major histocompatibility complex antigens and Ii by radioiodination, biotinylation, and membrane immunofluorescence
Authors: Elliott William L. , Sorli Christopher H. , Reisert Patricia S. , Humphreys Robert E.
Published: February 2007

Antibodies to either Ii or class II major histocompatibility complex (MHC) antigens did not recognize cell surface forms of Ii in immunoprecipitates of cells that had been radioiodinated by the lactoperoxidase method, whereas they bound [35S]methionine metabolically labeled molecules. N‐hydroxysuccinimidobiotin (NHS‐B) and biotin hydrazide (B‐H) were used to react more generally with cell surface proteins via amino groups and nitrene coupling, respectively. Each of these latter compounds labeled α and β chains of class II MHC antigens as seen in Western‐blotted, electrophoresed immunoprecipitates probed with 125I‐labeled streptavidin but not Ii or its associated forms. Although tyrosine residues might have been inaccessible to radioiodination in carbohydratederivatized forms of Ii, the lack of Ii biotinylation in these controled, sensitive studies was consistent with the view that Ii forms were not surface expressed, with the possible exception of the chondroitin sulfate‐derivatized forms of Ii (Ii‐CS).
Pseudothrombocytopenia induced by a monoclonal IgM kappa platelet agglutinin
Authors: Hoyt Robert H. , Durie Brian G. M.
Published: February 2007

Pseudothrombocytopenia is an in vitro phenomenon usually associated with anticoagulant (EDTA)‐dependent IgG platelet agglutinins. A low Coulter platelet count was investigated in a 63‐year‐old woman with multiple sclerosis and a monoclonal IgM kappa gammopathy. An unusual type of EDTA‐ and temperature‐independent IgM platelet agglutinin was identified by in vitro agglutination of donor platelets and was removed by immunoabsorption.
Elevated urokinase‐type plasminogen activator level and bleeding in amyloidosis: Case report and literature review
Authors: Sane David C. , Pizzo Salvatore V. , Greenberg Charles S.
Published: February 2007

Hyperfibrinolytic states are reported to be a cause of bleeding in patients with amyloidosis. We reviewed the literature on excessive fibrinolysis in association with amyloidosis and report our findings from a patient with idiopathic amyloidosis who developed a bleeding diathesis. Coagulation laboratory studies indicated elevated plasminogen activator levels associated with a reduction of plasminogen and α2‐plasmin inhibitor (α2‐PI) levels. The level of tissue‐type plasminogen activator (t‐PA) inhibitor and t‐PA antigen were normal. However, the patient did have a five‐ to sevenfold increase in amidolytic activity for the urokinase substrate pyro‐Glu‐Gly‐Arg‐pNA (S‐2444). This case therefore represents a novel example of a hyperfibrinolytic state associated with amyloidosis caused by elevated urokinase‐type plasminogen activator (u‐PA). Epsilon‐amino caproic acid (EACA) therapy resulted in an increase in α2‐PI and plasminogen levels and effectively reduced the blood loss. Hyperfibrinolytic states in amyloidosis have now been reported to be due to elevated t‐PA and u‐PA and depleted t‐PA inhibitor.
Platelet glass bead retention is useful in monitoring response to 1‐deamino‐8‐D‐arginine‐vasopressin (d‐DAVP)
Authors: Zeigler Z. R.
Published: February 2007

Seven patients with a suspected mild bleeding disorder had consistently abnormal glass bead platelet retention. This was the only coagulation abnormality detected in six of these patients; the seventh individual showed evidence of mild von Willebrand disease. Nevertheless, platelets from the six that were studied behaved in a similar fashion in the two‐stage platelet retention assay of McPherson and Zucker. This indicated that their platelets were defective in maintaining repetitive platelet‐platelet interaction in the second phase of this assay but functioned normally in the first phase. Their one‐stage platelet retention defects consistently normalized following the infusion of 1‐deamino‐8‐D‐arginine‐vasopressin (d‐DAVP). The duration of response was variable and easily defined by monitoring this parameter. These findings suggest platelet retention analysis may be useful in identifying mild bleeding disorder patients, who may benefit from d‐DAVP.
Interstitial deletion of chromosome 5, del(5q), in a newborn with down syndrome and an unusual hematologic disorder
Authors: Adams Roberta H. , Lemons Richard S. , Thangavelu Maya , Beau Michelle M. Le , Christensen Robert D.
Published: February 2007

A newborn with Down syndrome was noted on the 1st day of life to have an elevated white blood cell count of 79,900/mm3 with 62% lymphoblasts and a platelet count of 61,000/3, consistent with either transient myeloproliterative disorder of Down syndrome (TMD) or acute leukemia. Karyotype analysis of a bone marrow aspirate revealed that 20% of the cells had a 47,XY, + 21 karyotype, and 80% had a 47,XY, + 21, del(5)(q13q31) complement. Cytochemical and immunophenotyping of the peripheral blasts were consistent with the presence of an acute undifferentiated precursor blast clone. Results of clonogenic assays of hematopoietic progenitors from this patient's bone marrow were similar to those of patients with TMD. This patient's hematologic abnormalities resolved spontaneously without treatment by week 10 of life. This is the first report of an interstitial deletion of 5q associated with a hematologic abnormality present in an infant at birth.
Bone marrow aplasia associated with proliferation of large granular lymphocytes and subsequent transformation to acute lymphoblastic leukemia
Authors: Schiller Gary J. , Naeim Faramarz , Champlin Richard E.
Published: February 2007

Proliferation of large granular lymphocytes may be associated with neutropenia and, less frequently, thrombocytopenia. In this report, we describe a patient with severe aplastic anemia in the setting of a proliferation of cells with natural killer (NK) phenotype. We demonstrated evolution to acute lymphoblastic leukemia by cells of identical phenotype.
Cell‐mediated suppression of human hematopoiesis: Evaluation by limiting‐dilution analysis of hematopoietic progenitors
Authors: Takaue Yoichi , Reading Christopher L. , Watanabe Tsutomu , Kawano Yoshifumi , Ninomiya Tsuneo , Iishi Yashuhiko , Kosaka Masaaki , Shimizu Eiji , Ichioka Takao , Hosoda Teizoh , Suzue Takeshi , Abe Takanori , Koyama Tetsuya , Kuroda Yashuhiro , Dicke Karel A.
Published: February 2007

We have used limiting‐dilution clonal analysis (LDA) in microwells to study the inhibitory effects of T lymphocytes (T‐cells) or natural killer (NK) cells on human marrow progenitor cell growth. In four subjects with normal hematopoiesis, the growth of progenitors showed single‐hit kinetics both before and after T‐cell removal, indicating that, in the presence of colony‐stimulating activity, T‐cells have no effect on progenitor growth. In a patient with marrow hypoplasia associated with thymoma, hypogammaglobulinemia, and an increased number of suppressor T‐cells (Good's syndrome), the progenitor growth deviated from linearity, demonstrating the presence of cells with suppressor activity. After T‐cells were removed from this sample, the progenitor growth showed single‐hit kinetics. The suppressive action of E‐rosette‐positive cells with NK or cytotoxic activities was also suggested in a patient with severe combined immune deficiency and in a patient with T± lymphocytosis. Poor progenitor‐cell growth in three other patients with aplastic anemia was not significantly altered by T‐cell removal. Thus, LDA of human hematopoietic progenitors is useful for evaluating cell‐mediated interactions affecting hematopoiesis. This method may facilitate elucidation of mechanisms of myelosuppression in clinical settings.
Use of DDAVP in inherited and acquired platelet dysfunction
Authors: Dimichele Donna M. , Hathaway Wm. E.
Published: February 2007

Twenty‐one patients with prolonged bleeding times secondary to inherited disorders of platelet function and eight patients with prolonged bleeding times secondary to acquired platelet dysfunction were given 0.3 μg per kilogram of DDAVP, 1‐deamino‐8‐D‐arginine vasopressin, intravenously. Sixteen of twenty‐two DDAVP trials in patients with inherited platelet dysfunction (73%) and seven of the nine DDAVP trials in patients with acquired platelet dysfunction (78%) resulted in normalization or shortening of the prolonged bleeding times by at least 4 min. The bleeding time response did not correlate with changes in the levels of von Willebrand factor (vWf) antigen or ristocetin cofactor activity, nor was it associated with changes in vWf multimeric analysis or in vitro platelet aggregations following the administration of DDAVP. Shortening of the bleeding time with DDAVP was seen in patients with a failure to release/storage pool type defect, thromboxane synthesis type defect, Bernard‐Soulier syndrome, Glanzmann's thrombasthenia, the May‐Hegglin anomaly, liver disease, nonuremic renal disease, myelofibrosis, and Tangier's disease.
Porphyria cutanea tarda after allogeneic bone marrow transplantation for chronic myelogenous leukemia
Authors: Guyotat D. , Nicolas J. F. , Augey F. , Fiere D. , Thivolet J.
Published: February 2007

A case of porphyria cutanea tarda (PCT) occurring after bone marrow transplantation (BMT) is reported. A 43‐year‐old male with chronic myelogenous leukemia received an human leukocyte antigen (HLA)‐identical allogeneic transplantation with T‐cell depleted marrow. Because of graft rejection, a second transplant was performed 4 months later. A grade II acute graft‐ vs.‐host disease and a cytomegalovirus (CMV) infection were subsequently observed. Two years after the second transplant, cutaneous symptoms of PCT with typical biochemical abnormalities developed. Liver biopsy revealed signs of hepatitis with iron overload. CMV was isolated from liver tissue. The possible roles of underlying disease, BMT, and CMV liver disease are discussed in view of the recently reported cases of PCT in patients with AIDS or hematological disorders.
Varied expressions of receptors on the human megakaryoblastic cell line MEG‐01 by monoclonal antibodies
Authors: Imamura Nobutaka , Mtasiwa Deodatus M. , Inada Tominari , Kuramoto Atsushi , Ogura Michinori , Saito Hidehiko
Published: February 2007

We herein describe the regulation of specific receptors on the megakaryoblastic cell line MEG‐01 by means of fluorescence‐activated cell sorting (FACS IV) with a panel of monoclonal antibodies (MAbs). MEG‐01 cells expressed GpIIb/IIIa (CD41a) and OKM5 (CD36) antigens on their cell surface, whereas they showed only a little expression of GPIb (CD42b), suggesting that these are megakaryoblastic cells.

The up regulation of von Willebrand factor receptor (GPIb) and thrombospondin receptor (GPIV) and the down regulation of fibrinogen receptor (GPIIb/IIIa) and C3bi receptor (CD11b) were found by incubation with MAbs AN51 (CD42b), OKM5 (CD36), J15 (CD41a), and OKM1 (CD11b), respectively. This phenomenon was enhanced in the Ca2+ containing medium, except for the experiment with OKM5 (CD36) MAb. We thus suggest that several kinds of receptors on the surface of MEG‐01 cells are dexterously regulated through stimulation from outside the cell.
Serum transferrin receptor measurements in hematologic malignancies
Authors: Klemow Dawn , Einsphar David , Brown Todd A. , Flowers Carol H. , Skikne Barry S.
Published: February 2007

An enzyme‐linked immunosorbent assay using specific monoclonal antibodies was used to measure circulating transferrin receptor (TR) in 87 patients with various hematologic malignancies. The mean serum TR was significantly elevated in patients with myeloproliferative disorders (15.47 ± 12.54 μg/ml), whereas there were no differences in chronic granulocytic leukemia (7.89 ± 3.56 μg/ml), myelodysplastic disorders (9.25 ± 4.73 μg/ml), and acute nonlymphocytic leukemia (3.85 ± 3.50 μg/ml) as compared to normal (5.63 ± 1.42 μg/ml). Among patients with lymphoproliferative disorders, the mean level was normal in lymphoma (5.73 ± 2.59 μg/ml), multiple myeloma (5.47 ± 1.31 μg/ml), and hairy cell leukemia (7.04 ± 3.69 μg/ml). The serum TR was significantly elevated in chronic lymphocytic leukemia (CLL; 14.17 ± 12.29 μg/ml), and the serum levels reflected the clinical stage of the disease. These findings suggest that serum TR measurement may provide a useful laboratory index of disease activity in certain disorders such as CLL, whereas it most likely reflects the intensity of erythropoiesis in the remaining hematological disorders that were evaluated in this study.
Human immunodeficiency virus‐1 disease progression in hemophiliacs
Authors: Becherer Paul R. , Smiley M. Lynn , Matthews Thomas J. , Weinhold Kent J. , McMillan Campbell W. , White Gilbert C.
Published: February 2007

A retrospective study of 153 hemophiliacs infected with human immunodeficiency virus‐1 (HIV‐1) was performed to determine the clinical and immunological consequences of HIV‐1 infection and the markers and cofactors associated with these changes. Nearly 80% of HIV‐1‐infected hemophiliacs have developed a significant reduction in their CD‐4+ counts (<400 CD‐4+ cells/mm3) with 40% having less than 200 CD‐4+ cells/mm3 by the end of 1987. The rate of CD‐4+ cell count decline was slightly greater in patients who have already developed the acquired immunodeficiency syndrome (AIDS) compared to those who have not (50 vs. 31 cells/mm3/6 months). Thrombocytopenia and older age were associated with a more rapid CD‐4+ count deterioration, but the quantity of clotting factor utilized did not affect immunologic progression. In patients with < 200 CD‐4+ cells/mm3, the incidence of AIDS was significantly higher in adults (>21 years old) compared to children/adolescents. Cytomegalovirus (CMV) seroprevalence increased with age but did not correlate with the amount of concentrated clotting factor used. Although there was no relationship between CMV status and progression to AIDS, CMV‐seropositive patients were older and had a lower CD‐4+ count. Thus the majority of HIV‐1‐infected hemophiliacs are developing progressive immune dysfunction measured by CD‐4+ count decline. This drop in CD‐4+ count significantly correlates with a risk for the development of AIDS in adults but not in children (<21 years old).
Responsiveness of bone marrow erythropoietic stem cells (CFU‐E and BFU‐E) to recombinant human erythropoietin (rh‐Ep) in vitro in aplastic anemia and myelodysplastic syndrome
Authors: Aoki Isao , Homori Masashi , Chikazawa Hiroo , Ishikawa Kyozo , Higashi Katsumi
Published: February 2007

Responsiveness of bone marrow erythropoietic stem cells (CFU‐E and BFU‐E) to recombinant human erythropoietin (rh‐Ep) was examined in vitro in 23 patients with aplastic anemia and 14 with myelodysplastic syndrome (MDS) to investigate the clinical use of rh‐Ep for these diseases. Bone marrow mononuclear cells were cultured by methylcellulose methods for CFU‐E and BFU‐E assays. In normals, the CFU‐E numbers reached a plateau of increase at Ep doses of almost 2–5 units, and no further increase was observed with the addition of larger Ep doses. In aplastic anemia, the responses of CFU‐E to Ep were relatively good in nonsevere type and generally poor in severe type. However, the CFU‐E numbers increased with increasing doses of Ep in some of the patients with aplastic anemia. Among the patients with MDS, the responses of CFU‐E to Ep were relatively good in primary acquired refractory anemia (PARA) and primary acquired sideroblastic anemia. On the other hand, the responses of CFU‐E to Ep were poor in refractory anemia with an excess of blasts (RAEB) and RAEB in transformation among the MDS patients. BFU‐E responses to Ep were poor in severe aplastic anemia, RAEB, and RAEB‐T. However, there are Ep responsive patients in some of aplastic anemia and PARA. High titers of rh‐Ep were suggested to be effective clinically in some patients with aplastic anemia and those with PARA.
Effect of a factor VIII concentrate on type IIB von willebrand's disease‐associated thrombocytopenia presenting during pregnancy in identical twin mothers
Authors: Ieko Masahiro , Sakurama Shoki , Sagawa Akira , Yoshikawa Megumi , Nakagawa Shoichi , Satoh Masahiro , Yasukouchi Taro
Published: February 2007

Marked thrombocytopenia developed during pregnancy in both identical twins mothers who had systemic lupus erythematosus (SLE) and also type IIB von Willebrand's disease (vWD).

The proband's platelet count decreased in the third trimester of pregnancy. Large‐dose γ‐globulin and prednisolone treatments were performed because of the suspicion of immune thrombocytopenic reaction associated with SLE. These treatments were not effective. Her platelet count returned to the normal range immediately after delivery. Postpartum examinations revealed the decreased ristocetin cofactor activity and the deficiency of large von Willebrand factor (vWF) multimers in preserved plasma samples from the third trimester. These abnormal findings improved after delivery. Investigation of family members revealed that the proband had inherited type IIB vWD from her mother.

The other twin, who was also under treatment for SLE, became pregnant about 1 year after delivery in the proband and followed almost the same course as that observed in the proband. As bleeding tendency was observed a few days before delivery, a factor VIII concentrate (Haemate P) was administered to compete with her variant vWF. This concentrate could prevent the further decrease in her platelet count, thereby correcting the hemorrhagic tendency. It seems evident that factor VIII concentrate would be effective in treating thrombocytopenia associated with type IIB vWD.
Polymerase chain reaction amplification applied to the direct detection of a 4 bp deletion in the promoter region of the Aγ gene
Authors: Manca Laura , Cocco Elena , Masala Bruno , Gilman John G.
Published: February 2007

We report here the identification of a 4 bp deletion in the AγT globin gene promoter by means of Fnu4Hl digestion of DNA amplified by polymerase chain reaction (PCR). This deletion has been previously associated with haplotype II β‐thalassemia in Sardinia. This simple, non‐radioactive procedure should facilitate the screening of various populations of normal and β‐thalassemic subjects for this specific genetic alteration.
Thrombocytopenic purpura in HIV‐seronegative users of intravenous cocaine
Authors: Koury Mark J.
Published: February 2007

Severe thrombocytopenic purpura occurred in seven patients who had histories of recent or current intravenous cocaine use. All of the patients denied heroin use and all were seronegative for antibodies to the human immunodeficiency virus (HIV). The seven patients had normal or increased numbers of megakaryocytes in their bone marrows. While receiving corticosteroid therapy their platelet counts rose to 1011/L over periods ranging from 5 to 11 days. In view of the widespread use of cocaine, severe thrombocytopenia in the HIV‐seronegative patient should suggest the possibility of current or recent intravenous use of cocaine.
Evidence for the synthesis of embryonic globin chains in adult erythroid progenitor cells
Authors: Bhaumik Kabita
Published: February 2007

Embryonic globin chains were found to be synthesized in vitro by the BFU‐E colonies derived from adult sickle cell anemia (SS) patients, their heterozygous relatives as well as a few normal controls. In the absence of sufficient material for conducting direct structural analyses of these peptides, they were confirmed by evaluating the co‐migration of the ϵ‐ and ζ‐chains with the corresponding structurally characterized globin chains obtained from K562 cell lysates on a reversed phase high performance liquid chromatogram. The presence of ζ‐chain was also confirmed using an immunologic procedure. Furthermore, significant 35S‐methionine incorporation peak was observed corresponding to the ζ‐chain synthesized by the BFU‐E‐derived colonies implying an active synthesis of this embryonic globin chain in BFU‐E cells obtained from hemopoietically adult persons.
Cyclosporine for the treatment of granulocytopenia in Felty's syndrome
Authors: Canvin Janice M. G. , Dalal Bakul I. , Baragar Fletcher , Johnston James B.
Published: February 2007

A patient with Felty's syndrome was treated with cyclosporine, initially 10 mg/kg/day and then 4 mg/kg/day. The neutrophil count increased by 6 weeks and was normal at 3 months. Over the subsequent 27 months the neutrophil count was closely related to the cyclosporine dosage and there was no evidence of cyclosporine toxicity. This case indicates that cyclosporine may have a role in the treatment of Felty's syndrome.
Incidence and clinical characteristics of hereditary disorders associated with venous thrombosis
Authors: Tabernero Maria Dolores , Tomas Jose Francisco , Alberca Ignacio , Orfao Alberto , Borrasca Antonio Lopez , Vicente Vicente
Published: February 2007

At present, different congenital defects in several proteins—antithrombin III (AT III), protein C (PC), protein S (PS), and plasminogen (PLG)—are known to be causes of hereditary predisposition to thrombosis (thrombophilia).

The incidence of these hereditary disorders in our 204 patients (106 males and 98 females) with venous thromboembolism were 4% (three cases deficient in PC, three in PS, two in PLG, and one patient in AT III). Their families were studied. In all cases the disorders were inherited as an autosomal dominant trait.

The first thrombotic episodes occurred at a age of below 40 years. There was no relationship between protein levels and the occurrence of thrombosis, although a significant relationship was observed between a positive history of thromboembolic disease and a diagnosis of protein deficiencies.

We evaluated the differences between primary thrombosis and secondary thrombosis. The most common thrombotic sites were the deep veins. There were no differences between males and females. Evaluation of PC, PS, AT III, and PLG in patients with thromboembolic disease should be considered.
Plasmin generation and fibrin(ogen)olysis following desmopressin infusion
Authors: Takahashi Hoyu , Tatewaki Wataru , Wada Ken , Niwano Hiroe , Hanano Masaharu , Shibata Akira
Published: February 2007

Desmopressin acetate (DDAVP) is known to stimulate the release of tissue‐type plasminogen activator (t‐PA) from endothelial cells, but it is unclear whether the increased t‐PA actually elicits the plasmin generation and fibrin(ogen)olysis in the circulating blood. We measured plasma levels of plasmin‐α2‐plasmin inhibitor complex, fibrinogen degradation products (FgDP) and fibrin degradation products (FbDP) following desmopressin infusion in 19 patients with bleeding disorders or thrombophilia. Administration of desmopressin (0.3–0.4 μg/kg) produced a 4.0‐fold increase in plasmin‐α2‐plasmin inhibitor complex at 30 min, whereas neither FgDP nor FbDP was elevated significantly. These findings indicate that desmopressin infusion provokes the generation of plasmin in vivo, but most of the plasmin generated is complexed to α2‐plasmin inhibitor and does not degradate fibrin or fibrinogen.
Functional p75 interleukin‐2 receptor expression on the fresh blast cells in childhood acute lymphoblastic leukemia with natural killer cell properties
Authors: Ichikawa Motoki , Kawai Hiroshi , Komiyama Atsushi , Tsudo Mitsuru , Miyasaka Masayuki , Kinoshita Akitoshi , Nakazawa Shinpei
Published: February 2007

Neoplastic cells of childhood acute lymphoblastic leukemia (ALL) with natural killer (NK) cell properties were studied for the expression of p75 interleukin‐2 receptors (IL‐2R) and the receptor functions. Freshly prepared blast cells from a patient with ALL had NK cell properties: (1) the phenotype such as CD56+, CD2+, E‐rosette+, CD3−, and CD19−; and (2) the presence of spontaneous cytotoxicity against NK‐sensitive K562 target cells. Although p55 Tac antigen was not detectable, there was the expression of p75 IL‐2R on the freshly prepared blast cells: 70% of the cells reacted with Mik‐β1 monoclonal antibody against p75 IL‐2R as determined by flow cytometry. Two‐color flow cytometry revealed that the blast cells expressed both p75 IL‐2R and NKH‐1. NK activity of the blast cells was augmented by their treatment with 1,000 U/ml recombinant IL‐2 (rIL‐2): the cytotoxicity level as percentage lysis increased to 38.7% from 22.0% when the normal lymphocyte value increased to 62.1% from 46.2%. Although the blast cells possessed no apparent level of proliferative capacity, the addition of 1,000 U/ml rlL‐2 yielded a 2.7‐fold increase in their thymidine uptake. These results demonstrate the expression of functional p75 IL‐2R on the patient's blast cells with NK cell properties.
Heparin‐induced thrombocytopenia and thrombosis: Reversal with streptokinase a case report and review of literature
Authors: Mehta Daksha P. , Yoder Ernest L. , Appel Joel , Bergsman Kenneth L.
Published: February 2007

Heparin‐induced thrombocytopenia and thrombosis is associated with a significant incidence of morbidity and mortality. Prompt recognition of this complication and immediate withdrawal of heparin therapy are imperative. This report describes a case of heparin‐induced thrombosis and thrombocytopenia with major vascular insufficiency of the extremities. This is the first reported instance of the use of intravenous streptokinase for the treatment of heparin‐induced venous thrombosis.
A new frameshift β°‐thalassemia mutation (codons 27–28 +C) found in a Chinese family
Authors: Cai Shiping , Chui David H. K. , Ng Judy , Poon Annette O. , Freedman Melvin H. , Olivieri Nancy F.
Published: February 2007

A new β°‐ halassemia mutation, a frameshift mutation with an insertion of a single cytosine nucleotide in codon 27–28, is described. The propositus, who is compound heterozygous for this mutation and the IVSII‐654 C→T β°‐thalassemia mutation, has the phenotype of severe β‐thalassemia major.
Low‐dose subcutaneous erythropoietin in continuous ambulatory peritoneal dialysis
Authors: Rotellar C. , Mazzoni M. J. , Mosher W. F. , Aminrazavi M. , Bauer A. , Rakowski T. A. , Schreiner G. E. , Winchester J. F.
Published: February 2007

We evaluated changes in hematocrit in patients on continuous ambulatory peritoneal dialysis (CAPD) before and after the administration of erythropoietin (EPO). Thirty‐five patients were evaluated at the beginning of treatment with CAPD and after an average of 3.5 years on CAPD; mean hematocrit (Hct) rose from 25.4 ± 5.4% to 28.1 ± 6.7% (P < 0.001). In the period before EPO administration 11 patients required a total of 44 transfusions (one patient needed 23 transfusions). Fifteen patients were started on subcutaneous erythropoietin 3,000 units 3 times a week and were followed for a mean period of 6.3 months. Hct rose from 23.8 ± 1.8% to 25.2 ± 2.4% (P < 0.01) within the first 2 weeks and up to 27.5 ± 3.7% (P < 0.01) in the fourth week. By the eighth week the target Hct (30 to 35%) was reached. During the next 5 months the EPO doses were adjusted to each patient's needs ranging between 2,000 U per week to 4,000 U 3 times per week. Mild hypertension was the only side effect seen in some of the patients. In conclusion low dose subcutaneous EPO is effective in managing the anemia of patients on CAPD with only minor side effects.
GM‐CSF in the treatment of Felty syndrome
Authors: Joseph Geetha , Neustadt David H. , Hamm John , Kellihan Michael , Hadley Terence
Published: February 2007

Many therapeutic agents have been tried with variable success in the treatment of Felty neutropenia, but the reports are anecdotal. We now describe the second trial of recombinant granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), in a splenectomized, infected patient with Felty syndrome.
Benign familial thrombocytosis
Authors: Williams Eliot C. , Shahidi Nassrolah T.
Published: February 2007

A 13‐year‐old girl was found to have a platelet count in excess of 4 million/μl while being evaluated for a minor bleeding episode. Her father and two sisters also had thrombocytosis. All four affected patients were asymptomatic and had no clinical or laboratory evidence of a myeloproliferative disorder other than an elevated platelet count. This represents the second reported instance of benign familial thrombocytosis.
On the temporal development of erythrocyte sedimentation rate using sealed vacuum tubes
Authors: Kallner Anders
Published: February 2007

The temporal development of the erythrocyte sedimentation rate (ESR) was studied in wide, short vacuum tubes. It was found that in about 3% of the specimens arriving in the laboratory the ESR developed in three different phases during 60 min, whereas the other showed only two. The specimens with three phases behaved similarly in the Westergren method. It was shown that the Westergren ESR can be estimated with an acceptable accuracy already from measurements obtained after 30 min. Reproducibility and precision were improved by using a special instrument. Several advantages by this procedure were recognized, e.g., quicker results, identification of several otherwise missed rapid ESR. Accurate timing of the readings further improves accuracy and precision, and permits estimation of ESR (Westergren) up to 100 mm. In view of the obvious phases in the development of the ESR, it is proposed that this abbreviation is interpreted as erythrocyte sedimentation reaction and that the kind of quantity that is length is expressed in mm.
Heterogeneity of peripheral blood reticulocytes: A flow cytometric analysis with monoclonal antibody HAE9 and thiazole orange
Authors: Mechetner Eugene B. , Sedmak Daniel D. , Barth Rolf F.
Published: February 2007

The expression of a human erythroid cell surface antigen recognized by monoclonal antibody (mAB) HAE9 has been studied on peripheral blood reticulocytes by one‐ and two‐color flow cytometry. Total reticulocyte count was determined using Thiazole Orange (TO) and flow cytometry. In normal individuals, 4.56% of reticulocytes were stained by FITC‐labeled mAB HAE9. The correlation between reticulocyte percentage by TO and HAE9 staining was 0.828 (P < 0.0001) in patients with hematocrits less than 0.25. A HAE9‐positive reticulocyte percentage of 6–44% was observed when analyzed by two‐color flow cytometry with TO and mAB HAE9. These findings, in conjunction with previous studies, suggest that mAB HAE9 recognizes an early, less differentiated population of peripheral blood reticulocytes. Enumeration of immature reticulocytes may be of clinical utility.
Skin necrosis following prolonged administration of coumarin in a patient with inherited protein S deficiency
Authors: Goldberg Stuart L. , Kessler Craig M. , Yalisove Barbara L. , Elgart Mervyn L. , Orthner Carolyn L.
Published: February 2007

Depression of the vitamin K‐dependent modulators of coagulation during the initial phase of oral anticoagulant therapy may lead to a transient hypercoagulable state and skin necrosis. We report a case of skin necrosis associated with inherited protein S deficiency following prolonged coumarin therapy. As a result of a stasis ulceration causing a rise in c4b binding protein and concurrent treatment with topical sulfonamide, we hypothesize that a precipitous decrease in free protein S led to skin necrosis. Progression of the necrosis was halted with unactivated prothrombin complex concentrate. This case confirms the rare association between coumarin induced skin necrosis and protein S deficiency and emphasizes potential drug interactions.