bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of cytotoxic NK cells in peripheral blood and bone marrow of patients with acute myelogenous leukemia after continuous infusion with recombinant interleukin‐2
Authors: Lotzová Eva , Savary C. A. , Schachner J. R. , Huh J. O. , McCredie K.
Published: February 2007

We have studied the cytotoxic profile and distribution of lymphocyte subsets of patients with acute myelogenous leukemia in second remission, after continuous infusion with recombinant interleukin‐2 (IL‐2). The patients received repetitive cycles of 1–1.25 × 106 U/m2/day of IL‐2, given as 4 days continuous intravenous infusion followed by a 3‐day treatment‐free interval for the first 4 weeks. Patients receiving >4 cycles were treated with the same dose of IL‐2 continuously for 4 days, followed by a 10‐day treatment‐free interval. These studies showed that IL‐2 treatment resulted in the generation of peripheral blood cytotoxic activity against both NK‐susceptible, K‐562, and NK‐resistant Daudi cell lines. In most patients, enhancement of lytic activity increased with the number of IL‐2 infusions. The cytotoxicity in some patients increased as much as 700‐fold and 830‐fold against K‐562 and Daudi cells, respectively. It is of importance that oncolytic activity was also induced in bone marrow compartment (up to 182‐fold against K‐562). Some decline in cytotoxicity was observed within 14 days after initiation of IL‐2 infusion in peripheral blood, but high levels of lytic activity persisted at this time in bone marrow. It is of interest to note that the cytotoxicity of in vivo IL‐2 primed lymphocytes was further potentiated by IL‐2 in vitro. Importantly, the cytotoxic cells induced in vitro displayed lytic activity against fresh leukemic blasts. Phenotypic analysis demonstrated that CD3−, CD56+ NK cells were significantly increased by in vivo IL‐2 treatment (34 to 47‐fold in absolute numbers), while CD3+, CD56+ T‐cell subset remained low. Characterization of cytotoxic cells using the complement‐dependent assay and monoclonal antibodies indicated that both the in vivo‐induced and ex vivo‐potentiated lytic function was mediated by CD3−, CD56+, CD16+/– NK cells.
Lymphomas following cardiac transplantation. Case report and review of the literature
Authors: Sklarin Nancy T. , Dutcher Janice P. , Wiernik Peter H.
Published: February 2007

The success of allogeneic organ transplantation is in great part due to pharmacologic advances in the area of immunosuppressive therapy. However, this achievement has been attained at the price of an unexpectedly high incidence of malignancies in this transplant population. Lymphoid malignancies predominate in this and other immunodeficiency states. There is some controversy in the literature over the clonal or malignant nature of these proliferations. This paper presents a case of Burkitt‐like lymphoma occurring after cardiac transplantation. The role of Epstein–Barr virus in the pathogenesis of this disorder is reviewed as are multidisciplinary approaches to its management.
Amegakaryocytic thrombocytopenia of 4 years duration: Successful treatment with antithymocyte globulin
Authors: Trimble Malcolm S. , Brain Michael C. , Glynn Michael F. X.
Published: February 2007

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare cause of thrombocytopenia. Since it is a syndrome of diverse etiologies, the optimal treatment is often uncertain. In a patient with longstanding AATP, a complete remission was obtained with antithymocyte globulin.
Refractory ascites in the chronic myeloproliferative syndrome: A case report
Authors: Jacobs Peter , Wood Lucille , Robson Simon
Published: February 2007

In a patient with myelofibrosis, tense ascites refractory to conventional therapy resulted from extensive seeding of the peritoneum with colonies of extramedullary haematopoiesis. Whole abdominal radiation was found to be effective and well tolerated, and brought about prompt and lasting resorption of the exudate, with weight reduction and improvement in performance status from 50% to 90% on the Karnofsky rating.
Light chain composition of serum granulocyte binding immunoglobulins
Authors: Shastri Kaushik A. , O'Connor Brian M. , Logue Gerald L. , Shimm David S. , Rustagi Pradip K.
Published: February 2007

Serum granulocyte binding IgG, IgM, and the light chain composition of granulocyte binding immunoglobulins were measured in 58 adult subjects, including 8 normal individuals, 6 with Felty syndrome, 6 with chronic idiopathic neutropenia, 32 with B‐cell chronic lymphocytic leukemia (CLL), and 6 with multiple myeloma. An abnormal kappa/lambda ratio of granulocyte binding immunoglobulins was detected in 12 of 32 patients with CLL. Neutropenia in patients with CLL did not correlate with an abnormal kappa/lambda ratio or excess granulocyte binding IgG, but did correlate with granulocyte binding IgM (P < 0.02). Eight of the 12 patients (5 with chronic idiopathic neutropenia and 3 with Felty syndrome) with an immune neutropenia without underlying neoplastic disorder had light chain restricted granulocyte binding immunoglobulins. Of all patients' sera with light chain restriction, 76% were of lambda light chain isotype. Thus, the frequent detection of light chain restriction of granulocyte binding immunoglobulins is not a reflection of malignancy but is suggestive of the somatic mutation of immunoglo‐bulin light chain genes.
Establishment of a new Epstein‐Barr virus nuclear antigen‐positive B‐cell line, BALL‐2, with t(8;14)(q24;q32) chromosome abnormality from B‐cell acute lymphoblastic leukemia, L2
Authors: Kubonishi Ichiro , Daibata Masanori , Yano Shoki , Isobe Masaharu , Kurosawa Nobuyuki , Nagumo Hideki , Ogita Zen‐Ichi , Ohyashiki Junko H. , Toyama Keisuke , Miyoshi Isao
Published: February 2007

A new Epstein‐Barr virus nuclear antigen (EBNA)‐positive B‐cell line, designated BALL‐2, was spontaneously established from the peripheral blood of a 14‐year‐old boy with an EBNA‐negative B‐cell acute lymphoblastic leukemia (B‐ALL), L2 in the French‐American‐British classification. The BALL‐2 cell line grew in suspension with or without forming clumps of cells. The cultured cells exhibited lymphoid morphology with indented or tabulated nuclei, prominent nucleoli, and relatively abundant cytoplasm. Immunologic and cytogenetic studies showed that the BALL‐2 cell line expressed the B‐cell phenotype, Cplg+, Smlg+, CD19+, CD20+, CD38+, la+, and had chromosome translocation, t(8;14)(q24;q32). The same phenotypic and chromosome markers were present in original leukemia cells. These results indicated that the cell line was derived from the patient's leukemia cells. Unexpectedly, however, BALL‐2 cells were positive for EBNA and EB virus DMA. Gene analysis of the BALL‐2 cell line showed biallelic rearrangements in the JH locus. One of the JH rearrangement comigrated with a rearranged c‐myc gene, indicating the translocation had occurred between JH and c‐myc loci. The t(8;14) abnormality is a known chromosome marker of Burkitt lymphoma and L3 type ALL. Our studies revealed that this translocation and myc gene rearrangement can also be found in L2 type B‐ALL.
Spinal cord compression secondary to extramedullary hematopoiesis: A noninvasive management based on MRI
Authors: Hassoun Hani , Lawn‐Tsao Lilly , Langevin Eugene R. , Lathi Ellen S. , Palek Jiri
Published: February 2007

We report the first case of spinal cord compression secondary to extramedullary hematopoiesis in which the diagnosis was made by magnetic resonance imaging (MRI). Based on the great advantage of this imaging test that visualizes the entire spine, the noninvasive approach to such patients, using low‐dose radiation therapy and guided by MRI is discussed. This management appears to be both efficacious and safe.
Expression of transferrin receptors on monocytes in hemochromatosis
Authors: Adams Paul C. , Chau Luan A. , White Martin , Lazarovits Andrew
Published: February 2007

To assess whether an abnormality in transferrin receptor expression or regulation could represent an underlying metabolic defect in the reticuloendothelial (RE) system in hemochromatosis, monocytes were analyzed for the expression of the transferrin receptor using a monoclonal antibody (Act II) to the transferrin receptor (CD71) and flow cytometric analysis. Hemochromatosis patients (n = 14), and normal volunteers with no clinical evidence of iron overload (n = 14) were studied. A significant inverse relationship was observed for the relationship between the expression of transferrin receptor on monocytes and log(hepatic iron concentration) in hemochromatosis patients (r = −0.59, P < 02) and also for the relationship between the expression of transferrin receptor and log(serum ferritin) in normal volunteers (r = −0.90, P <.001). There was no significant difference in the mean expression of monocyte transferrin receptor between hemochromatosis patients and normal volunteers. However, the expression of the transferrin receptor in hemochromatosis patients was disproportionately higher than would be predicted from the relationship between serum ferritin and transferrin receptor expression in normal volunteers. The inverse relationship of the monocyte transferrin receptor relative to body iron stores in hemochromatosis is consistent with observations in other tissues, and suggests that non‐transferrin iron metabolism, including ferritin, requires further investigation in the RE cell in hemochromatosis.
Intravenous gamma globulin decreases platelet‐associated IgG and improves transfusion responses in platelet refractory states
Authors: Zeigler Zella R. , Shadduck Richard K. , Rosenfeld Craig S. , Winkelstein Alan , Przepiorka Donna , Kiss Joseph E. , Duquesnoy Rene J. , Marrari Marilyn
Published: February 2007

In an attempt to improve platelet transfusion responses, intravenous immunoglobulin (IV‐IgG) was administered to 19 patients who were refractory to random and best available HLA‐matched platelets. A response to IV‐IgG was defined as two or more successive transfusions of HLA‐matched products that provided recoveries greater than 30%. Thirteen of 19 (68%) patients responded to therapy at a median time of 7 days after initiation of IV‐IgG (range = 2–17). Baseline platelet associated IgG levels (PaIgG) were elevated in both the responders (61.6 ± 76.2) (mean ± SD) and the non‐responders (47.0 ± 46.3 fg/plt). Post‐therapy, PaIgG levels remained unchanged in the nonresponders but were decreased significantly (p = 0.05) to 11.1 ± 6.2 fg/plt in the responders. The latter levels were similar to those (11.6 ± 8.2 fg/plt) measured in a series of 36 transfusion responsive patients. This apparent decline in PaIgG was not explained by differences in lymphocytotoxic antibodies (LCT‐Ab) after therapy. Moreover, a high degree of alloimmunization was associated with a poorer response to IgG. Only two of eight patients with LCT panel‐reactive antibody (PRA) of > 85% were responders. By contrast, improved transfusion outcomes were seen uniformly in patients with PRA ≦ 85%. Improved recoveries were obtained using LCT‐Ab compatible but not incompatible platelets. The median increment (% predicted) with compatible platelets before therapy was 6.0 ± 9.9 (SD). Post‐IgG, median recoveries were 37.0 ± 31.2 percent, P < 0.001. These findings suggest that IV‐IgG may alter destructive mechanisms that affect the survival of compatible platelets in refractory patients.
Reproducibility and temporal stability of ADP‐induced platelet aggregation: Comparison of the anticoagulants sodium citrate and D‐phenylalanyl‐L‐prolyl‐L‐arginyl chloromethyl ketone
Authors: Horne William C. , Cohen Donald J. , Anderson George M.
Published: February 2007

We compared the reproducibility and temporal stability of ADP‐induced aggregation of platelet‐rich plasma anticoagulated with citrate or with D‐phenylalanyl‐L‐prolyl‐L‐arginyl‐chloromethyl ketone (PPACK), a thrombin inhibitor. Citrate‐ or PPACK‐platelet‐rich plasma (PRP) was stored at room temperature in capped plastic tubes or in plastic syringes from which all air was expelled. At intervals over 1‐5 hr after venipuncture, platelet aggregation was induced by 1‐1.5 μM ADP. Initially, the aggregation of PPACK‐PRP was nearly twice that of citrate‐PRP. The response of PPACK‐PRP stored in the syringe remained essentially constant over the interval of study, in contrast to the responses of the other samples which declined with time. The improved stability of the response obtained from samples anticoagulated with PPACK was due to the a
citrate, since PRP containing both citrate and PPACK became less responsive over time a manner similar to PRP which contained only citrate. Anticoagulation with PPACK rather than citrate results in a more reproducible and stable aggregation response and more closely reproduces the in vivo environment of the platelet.
Hb S/β°‐Thalassemia due to the ˜1.4‐kb deletion is associated with a relatively mild phenotype
Authors: Waye John S. , Chui David H. K. , Eng Barry , Cai Shi‐Ping , Coleman Mary B. , Adams Junius G. , Steinberg Martin H.
Published: February 2007

We report a relatively mild phenotype associated with two siblings who are compound heterozygotes for Hb S and a β°‐thalassemia mutation due to a ˜1.4‐kb deletion of the 5′ region of the β‐globin gene. Each is found to have unusually high levels of Hb A2 and Hb F, accounting for more than 20% of the total hemoglobin. These may interfere with intracellular Hb 5 polymerization, thus leading to a mild clinical course.
Intravenous gammaglobulin treatment for immune thrombocytopenia associated with infectious mononucleosis
Authors: Cyran Elizabeth M. , Rowe Jacob M. , Bloom Robert E.
Published: February 2007

Severe thrombocytopenia is an uncommon (incidence <1%) but serious complication of infectious mononucleosis. Corticosteroids have been used for therapy with variable responses reported. Five consecutive patients with infectious mononucleosis‐related severe thrombocytopenia were treated with intravenous gammaglobulin (IVIG) at a dose of 400 mg/kg/day for 2–5 days. All patients appear to have had an immunologic or consumptive etiology for their thrombocytopenia as determined by increased marrow megakaryocytes. All patients were initially treated with oral prednisone 1 mg/kg/day. Due to the relatively slow response to prednisone (platelet count >20,000/γL on the 8th to 13th hospital day) or increased bleeding symptoms, IVIG was initiated. Four of the five patients rapidly developed significant increases in their platelet counts (range 44,000/γL to 97,000/γL). Two of these responses were sustained and two relapses occurred (while on continued steroid therapy) which again responded to booster doses of IVIG at similar doses. IVIG has been previously shown to be effective in treating patients with idiopathic thrombocytopenia purpura. Historically, patients with infectious mononucleosis‐related severe thrombocytopenia often are refractory to corticosteroid therapy and our limited experience suggests that IVIG may also be effective in infectious mononucleosis‐related severe thrombocytopenia.
Hematologic improvement in a patient with gaucher disease on long‐term enzyme replacement therapy: Evidence for decreased splenic sequestration and improved red blood cell survival
Authors: Parker Robert I. , Read Elizabeth J. , Barton Norman W. , Brady Roscoe O.
Published: February 2007

We describe here an investigation of the hematologic response of a child with Gaucher disease to a six‐year therapeutic trial of human placental mannose‐terminated glucocerebrosidase. While on enzyme replacement therapy, the patient's hemoglobin and platelet count significantly increased (6.9 g/dl to 12.2 g/dl, and 39,000/γL to 74,000/γL, respectively). Over the same time interval his absolute reticulocyte count decreased (88.1 × 103/γL to 31.5 × 103/γL). The patient's splenic volume decreased by over 60% (2108ml to 797ml) and his bone marrow demonstrated a dramatic clearing of Gaucher cell infiltration. Serum erythropoietin levels were at the lower range of normal at points in time when he was severely anemic and did not change with improvement in hemoglobin. Coincident with the improvement in the patient's hemoglobin, in vivo survival of autologous radiolabeled RBCs increased 34%. The improved hematopoietic profile appeared to result primarily from an increase in the in vivo survival of mature hematopoietic elements secondary to a decrease in splenic sequestration. Improved marrow function secondary to the clearing of Gaucher cell infiltrates may also playa role in his improved hematologic status.
Hyperammonemia following allogeneic bone marrow transplantation
Authors: Tse Nielson , Cederbaum Stephen , Glaspy John A.
Published: February 2007

Hyperammonemia is a rare and serious complication of intensive cytotoxic chemotherapy. We report the case of a patient who developed profound idiopathic hyperammonemia following bone marrow transplantation for chronic myelogenous leukemia. Despite rapid institution of hemodialysis, sodium benzoate, and the experimental agent sodium phenylacetate, the patient ultimately succumbed to complications of this metabolic derangement. The literature is reviewed, and recommendations for an approach to this complication of marrow transplantation are proposed.
Double heterozygosity of the β‐malay and a novel β‐thalassemia gene in a thai patient
Authors: Fucharoen Supan , Fucharoen Goonnapa , Laosombat Vichai , Fukumaki Yasuyuki
Published: February 2007

The β‐globin genes from a Thai patient compound heterozygous for β+‐ and β° thalassemias were investigated. Amplification and DNA analysis of genomic DNA by the polymerase chain reaction procedure permitted the identification of the β‐Malay mutation (β 19;AAC‐AGC) in one allele and a novel β°‐thalassemia mutation (41;TTC‐TT) in another allele.
Gelatinous transformation of marrow in a case of acute myelogenous leukemia post‐chemotherapy
Authors: Feng Chi‐Shun
Published: February 2007

Gelatinous transformation of marrow in a patient with acute myelogenous leukemia was reported. This case was at variance with other reported cases of gelatinous transformation of marrow in that a) it was associated with a primary bone marrow disease and b) there was no fat atrophy and the patient was not cachetic. The fact that it occurred abruptly post‐chemotherapy suggested that marrow hypoplasia induced by chemotherapy could be the cause of this lesion in this particular situation.
A novel α‐thalassemia‐2 (−2.7‐kb) observed in a chinese patient with Hb H disease
Authors: Zhao Jing‐Bo , Zhao Lin , Fei You‐Jun , Liu Jin‐Cai , Huisman Titus H. J.
Published: February 2007

We describe a newly detected α‐thalassemia‐2 (α‐thal‐2) deletion characterized by a small −2.7‐kb deletion involving the α1 globin gene. This deletion has thus far been observed in only one Chinese subject with Hb H disease.
Intravenous immunoglobulin in the treatment of human immunodeficiency virus‐related thrombocytopenia
Authors: Rarick Mark U. , Montgomery Terri , Mazumder Amitabha , Gill Parkash S. , Loureiro Carmen , Levine Alexandra M. , Groshen Susan , Sullivan‐Halley Jane , Jamin Denise
Published: February 2007

Fourteen patients with sexually transmitted human immunodeficiency virus (HIV)‐related immune thrombocytopenia were treated with intravenous gammaglobulin (IVIG). The patients were treated with a uniform program consisting of 1 g/kg of IVIG on day 1 and day 2, followed by 1 g/kg on day 15. Most patients had pretreatment bleeding symptoms, which included petechiae, spontaneous and traumatic ecchymoses, gum bleeding, and epistaxis. Median baseline platelet count was 17,000/mm3 (range 3–61,000/mm3). After the infusion of the IGIV, all patients had a resolution of their bleeding by day 8. The median maximum platelet count achieved with the IGIV was 220,000/mm3 (range 76–426,000/mm3). No patient achieved either a sustained complete or partial remission after the conclusion of the IVIG therapy. Toxicities were minimal with the majority being headache and nausea. In conclusion, patients with sexually transmitted HIV infection and immune thrombocytopenia respond favorably to IVIG. This treatment should be considered as first‐line therapy for patients with HIV‐related immune thrombocytopenia who require immediate but temporary increase in their platelet count, attributable to symptoms or signs of clinical bleeding or because of the need for an invasive procedure.
Plasma levels of soluble thrombomodulin increase in cases of disseminated intravascular coagulation with organ failure
Authors: Asakura Hidesaku , Jokaji Hiroshi , Saito Masanori , Uotani Chika , Kumabashiri Ichiro , Morishita Eriko , Yamazaki Masahide , Matsuda Tamotsu
Published: February 2007

We examined the changes in plasma levels of soluble thrombomodulin in 66 cases of disseminated intravascular coagulation (DIC), to investigate the damage to vascular endothelial cells and its relationship to multiple organ failure. A significant elevation of plasma levels of soluble thrombomodulin was observed in most cases of DIC, especially in patients with sepsis. However, no such significant elevation was observed in patients with acute promyelocytic leukemia. Plasma levels of both soluble thrombomodulin and active plasminogen activator inhibitor were higher in the cases of DIC with multiple organ failure than in those without multiple organ failure. The levels of soluble thrombomodulin were decreased with the clinical improvement in most cases of DIC but were further increased or remained at high levels in patients who showed no improvement of DIC. It was suggested that an increase in soluble thrombomodulin indicates the damage to the vascular endothelial cells in cases of DIC and that the damage to vascular endothelial cells plays some role in further progression of multiple organ failure.
An effective acute graft‐vs.‐host disease prophylaxis with minidose methotrexate, cyclosporine, and single‐dose methylprednisolone
Authors: Yau Jonathan C. , Huan Susan D. , Dimopoulos Meletios A. , Woo Shiao Y. , Brunner Lane J. , Wallerstein Ralph O. , Deisseroth Albert B. , Andersson Borje S. , Spencer Verneeda , Spitzer Gary , LeMaistre C. Frederick
Published: February 2007

Cyclosporine and methotrexate at standard doses (15 mg/m2on day 1 and 10 mg/m2on days 3, 6, and 11, total 45 mg/m2) are effective in the prophylaxis of actue graft‐vs.‐host disease. However, the combination has significant early toxicities with delayed engraftment, increased mucositis, and hepatotoxicity. We modified the combination by adding single‐dose methylprednisolone and lowered the total dose of methotrexate to 35 mg/m2(5 mg/m2on days 1, 3, and 6, and then 10 mg/m2on days 11 and 18) and then to 20 mg/m2(5 mg/m2on days 1, 3, 6, and 11) in an attempt to decrease these side effects in two sequential consecutive groups of patients. We demonstrated that the modified regimens maintained the efficacy with reduced toxicities. The rate of engraftment was comparable to cyclosporine alone and the hepatotoxicity was reduced with reduced doses of methotrexate. Factors such as early immunosuppression of the host, intravenous immunoglobulin, the timing of steroid administration, nucleotide free diet and germ free environment may contribute to the effectiveness of the combination and permit reduction of methotrexate dose.
Platelet thrombospondin and glycoprotein IV abnormalities in patients with essential thrombocythemia: Effect of α‐interferon treatment
Authors: Legrand C. , Bellucci S. , Disdier M. , Tobelem G. , Edelman L.
Published: February 2007

Platelet aggregability and some biochemical parameters were evaluated in seven patients with essential thrombocythemia (ET) compared with seven patients with secondary thrombocytosis (ST). Defective platelet aggregation with one or more agonists was seen in five patients with ET whereas aggregation was increased in two other patients. In addition, three patients with ET demonstrated spontaneous platelet aggregation in citrated plasma. This was associated with increased level of thrombospondin (TSP) in the plasma membrane. Interestingly, the presence of a proteolyzed 160 kDa form of TSP was detected in all patients with ET, whereas it was never found in patients with ST. Furthermore, three patients with ET demonstrated increased levels of platelet surface glycoprotein IV (GP IV), the putative receptor for TSP in the plasma membrane. In two of these patients, this correlated with increased surface expression of TSP and spontaneous platelet aggregation. The results suggest a possible link between the increased number of plasma membrane GP IV molecules, the spontaneous expression of TSP on the platelet surface and platelet hyperaggregability in some ET patients. The levels of plasma membrane GP IV and platelet surface‐associated TSP tended to be normalized during α‐interferon treatment, whereas the presence of an altered form of TSP persisted. This last parameter might be of practical usefulness in the characterization of the disease, permitting a clear distinction from ST.
Acute megakaryoblastic leukemia with translocation t(1;22)(p13;q13) in a 10‐week‐old infant
Authors: Washio Setsuko , Ido Masaru , Azuma Eiich , Fukui Masako , Shibata Takeo , Zhang Shao‐Li , Komada Yoshihiro , Ito Masahiro , Koike Tadashi , Kaneko Yasuhiko , Sakurai Minoru
Published: February 2007

A 10‐week‐old girl without Down syndrome developed an acute megakaryoblastic leukemia (AMKL). Bone marrow aspirates and biopsy showed megakaryoblastic infiltration with myelofibrosis. The diagnosis was made based on the findings that the positive reactions of leukemic cells to platelet peroxidase and to monoclonal antibodies which recognize platelet‐specific surface glycoprotein (GP) Ilb/IIIa and GP78. The blasts also showed myeloid and monocytoid differentiation antigens. The leukemic cells had a karyotype of 46,XX,t(1;22)(p13;q13). Our case and two other infantile cases reported by other investigators establish the novel association of the t(1;22) with AMKL.
Protein‐bound cobalamin absorption declines in the elderly
Authors: Scarlett John D. , Read Helen , O'Dea Kerin
Published: February 2007

A modified protein‐bound cobalamin absorption test was used to study dietary cobalamin absorption in healthy adults of different age groups and patients with isolated low serum concentrations of cobalamin. Dietary cobalamin absorption was significantly reduced in healthy adults aged 55‐75 years compared with young adults, with a further reduction in those older than 75 years. No difference was detected between dietary cobalamin absorption in patients with isolated low serum cobalamin and controls of a similar age group. Cobalamin malabsorption was associated with elevated serum gastrin. The diagnostic value of this protein‐bound cobalamin absorption test in the elderly was limited by the frequent finding of reduced absorption in healthy elderly people with normal serum cobalamin concentrations. The performance of such tests should be evaluated in different age groups before application in diagnosis.
Association of thyroid disease with acute leukemia
Authors: Moskowitz Craig , Dutcher Janice P. , Wiernik Peter H.
Published: February 2007

The purpose of this paper is to evaluate the possible clinical association of autoimmune thyroid disease and acute leukemia. This study is a retrospective review of all adult patients with acute leukemia treated at our institutions from 1978‐1989. Those with both leukemia and thyroid disease were evaluated and are presented. Twenty‐seven of eight hundred seventy patients with acute leukemia had evidence of thyroid disease. This is a 3‐fold increase in overall incidence. Twenty‐one patients had acute myeloid leukemia, five had acute lymphoid leukemia, and one had accelerated chronic myeloid leukemia. Thyroid diseaseentities included toxic multinodular goiter (four patients), idiopathic hypothyroidism (eight patients), Graves' disease (eight patients), and Hashimoto's thyroiditis (seven patients). Whereas the association may have had a negative effect on elderly patients, those with Graves' disease and Hashimoto's disease appeared to have an improved outcome of the leukemia. There is an increased association of autoimmune thyroid disease and acute leukemia. Since thyroid hormones are important regulators of hematopoiesis and utilize receptors similar to those of differentiating factors such as retinoids, the association may be important for further study of mechanisms of growth regulations in leukemia.
Severe osteopenia and vertebral compression fractures after complete remission in an adolescent with acute leukemia
Authors: Vassilopoulou‐Sellin Rena , Ramirez Irma
Published: February 2007

Acute leukemia frequently presents with skeletal symptoms; however, the etiologies of bone pain and osteopenia are poorly understood. We present the case of an adolescent girl with acute leukemia who developed vertebral fractures after being in complete remission for 3 months. Bone mineral density was very low (<0.6 g/cm2) but remained stable during the subsequent 3 months despite continuation therapy with methotrexate and prednisone. Findings of a bone biopsy were consistent with a recent episode of aggressive bone resorption. We suggest that paracrine secretion of lymphokines may mediate loss of bone mass during the active phase of acute leukemia, although clinical bone disease may not develop until after complete remission is achieved.
Fluctuations in serum cytokine levels in the patient with cyclic neutropenia
Authors: Yujiri T. , Shinohara K. , Kurimoto F.
Published: February 2007

The fluctuations of the levels of serum cytokines in a patient with cyclic neutropenia were studied. The greatest fluctuation was found in granulocyte colony‐stimulating factor (G‐CSF). Tumor necrosis factor‐α level fluctuated inversely with fluctuation of G‐CSF, and oscillation of interleukin (IL)‐6 level preceded that in G‐CSF level. It is likely that the variations of the levels of cytokines play a significant role in regulating hematopoiesis in cyclic neutropenia. Our results suggested that the stage of the granulocyte‐committed stem cell is the major step of the defect, and the defect at the stage of the multipotent stem cell or bone marrow microenvironment was also suggested.
Radioimmunoassay for the measurement of serum IL‐6 and its correlation with tumour cell mass parameters in multiple myeloma
Authors: Solary Eric , Guiguet Michel , Zeller Véronique , Casasnovas René‐Olivier , Caillot Denis , Chavanet Pascal , Guy Henri , Mack Gérard
Published: February 2007

Interleukin‐6 (IL‐6) was demonstrated to be a strong autocrine or paracrine plasmocytoma cell growth factor in humans. Using a bioassay, high serum IL‐6 (S‐IL‐6) levels were correlated with disease severity in plasma cell dyscrasias. Since other cytokines could interfere with the bioassays, we developed a specific radioimmunoassay to study S‐IL6 levels in 102 patients with monoclonal gammopathy (MG). S‐IL‐6 level was studied by a double antibody radioimmunoassay using a rabbit polyclonal anti‐IL‐6 antibody and a human recombinant IL‐6 as the standard. The lowest value of the standard significantly different from zero was found to be 78 pg/ml. Within‐run and between‐run precisions were characterized by a mean coefficient of variation of 3.72 and 5.5%, respectively. The mean analytical recovery was found to be 113% and the immunochemical identity of IL‐6 standard and S‐IL‐6 was shown by dilution tests. IL‐6 was detected in all tested sera. Sera from 66 healthy volunteers and 43 patients with acute leukemia or malignant lymphoma were tested as controls. In healthy subjects, S‐IL‐6 values were 294 ± 86 pg/ml. MG were classified as multiple myeloma (MM), macroglobulinemia, and MG of undetermined significance (MGUS). The distribution of S‐IL‐6 levels in patients with MG was significantly higher than in healthy subjects but lower than in patients with acute leukemia or Hodgkin's lymphoma. Results obtained in 55 patients with MM were related to other biological parameters. S‐IL‐6 levels correlated with bone‐marrow plasmacytosis (P < .0005), serum‐lactate dehydrogenase (S‐LDH; P < .005), serum β2 microglobulin (S −β2m; P < .01), and serum calcium (S‐Ca; P < .025) and inversely correlated with haemoglobin (P < .025). Our results indicate that 1 radioimmunoassay is suitable for the measurement of human IL‐6 in serum; 2 high S‐IL‐6 levels are observed in a small number of patients with MG; and 3 S‐IL‐6 level correlates with tumour cell mass in patients with overt MM.
Immunological evaluation of harvested stem cells obtained by leukapheresis after chemotherapy
Authors: Teixeira G. , Lenormand B. , Jean P. , Fardoun D. , Sumereau‐Dassin E. , Bastit D. , Tilly H. , Piguet H. , Monconduit M. , Vannier J. P.
Published: February 2007

Some patients suffering from malignancies may benefit of myeloablative chemotherapy followed by hematological reconstitution with autologous peripheral blood reinfusion. A quick evaluation of the number of hematopoietic progenitors present in leukapheresis blood samples is necessary to ensure the collection of a sufficient number of these cells. A study was performed on a series of 25 leukapheresis following initial chemotherapy.

The number of granulomonocytic colony‐forming unit (CFU‐GM) and the number of CD34+ cells were evaluated simultaneously, in each sample. Results have shown a relatively strong linear correlation between both methods of evaluation of hematopoietic progenitors, suggesting that immunophenotyping could be a useful method to estimate the number of progenitors.
Granular lymphocyte leukemia with pure red cell aplasia: Usefulness of gene analysis in assessing therapeutic effect
Authors: Motoji Toshiko , Yamada Osamu , Takahashi Masatomo , Oshimi Kazuo , Mizoguchi Hideaki
Published: February 2007

A patient with granular lymphocyte leukemia (GLL) of the CD3+, CD4‐, CD8+ phenotype accompanied by pure red cell aplasia (PRCA) is described. Surface marker analysis, nonmajor histocompatibility complex (MHC)‐restricted cytotoxicity assay, gene analysis, and in vitro colony assay were performed on the granular lymphocytes before and after treatment. Cyclophospharnide therapy was highly effective, and after remission clonal granular lymphocytes were no longer identified by T‐cell antigen receptor (TCR) gene analysis or surface marker analysis. Lymphocytes obtained after remission did not exhibit elevated levels of non‐MHC‐restricted cytotoxicity, nor did they demonstrate a suppressive effect on erythroid colony formation. TCR gene analysis proved to be a sensitive parameter for evaluating the residual malignant granular lymphocytes. Gene analysis will be useful both for timing the discontinuation of treatment and for the early detection of relapse. Various factors possibly related to the development of PRCA in this patient were investigated and their significance is discussed.
Vincristine therapy for thrombotic thrombocytopenic purpura
Authors: O'connor N. T. J. , Bruce‐Jones P. , Hill L. F.
Published: February 2007

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder characterized by micro‐ angiopathic haemolytic anemia, consumption thrombocytopenia, renal impairment, neu‐ rological dysfunction, and fever, but all these features are not present in every patient. Although the prognosis of TTP has improved since it was demonstrated that large volumes of fresh frozen plasma (FFP) lead to a remission in most patients, the disease remains fatal in many instances. Therefore, other therapies are often used in TTP, but there is skepticism about their value, since such treatments are often used in combination, making evaluation difficult. This report describes three patients with TTP and a consistent therapeutic response occurring 5 days after vincristine in each of four instances.
Epidermal growth factor binding sites on human erythrocytes in donors with different ABO blood groups
Authors: Engelmann Bernd , Schumacher Udo , Haen Ekkehard
Published: February 2007

Analysis of epidermal growth factor (125J‐EGF) binding to human red cells revealed the presence of two classes of binding sites with apparent equilibrium dissociation constants (app.Kd) in the 10−10−10−9 M and in the 10−8 M range, respectively. The number of binding sites/cell ranged between 600 and 2,400 for the high‐affinity binding site and between 7,200 and 23,000 for the low‐affinity site. No differences were seen in the apparent Kd values for both types of binding sites between red cells obtained from donors with different ABO‐blood groups. An increase in the number of high affinity EGF binding sites was observed in donors with blood group A,‐erythrocytes as compared to red cells taken from donors with blood groups o and B.
Effects of interleukin‐5 on acute myeloid leukemias
Authors: Baumann Michael A. , Paul Cassandra C. , Grace Michael J.
Published: February 2007

Because of the known activity of interleukin‐5 (IL‐5) as a growth factor for human eosinophils, we performed studies to ascertain whether M4Eo acute leukemia cells might be capable of responding to IL‐5. Surprisingly, short term incubation of freshly isolated M4Eo blasts with rhIL‐5 induced differentiation of the cells to macrophages. To determine whether other variants of acute myelogenous leukemia (AML) might also be capable of responding to IL‐5, we studied cells from four additional unselected cases and found that one responded to IL‐5 by vigorous proliferation. Using biotinylated rhIL‐5, second labelling with streptavidin‐fluorescein isothiocyanate (FITC) and flow cytometric analysis, specific binding of IL‐5 to both responsive leukemias was demonstrated, suggesting the presence of specific IL‐5 receptors. Additional study will be needed to assess the frequency of IL‐5 responsiveness in AML and to determine the relationship of these phenomena to the physiologic role of IL‐5 in the regulation of hematopoiesis.
Marrow transplantation for paroxysmal nocturnal hemoglobinuria
Authors: Kawahara K. , Witherspoon R. P. , Storb R.
Published: February 2007

Between 1971 and 1990, nine patients ranging in age from 14‐38 years received marrow transplants for paroxysmal nocturnal hemoglobinuria (PNH). Six were transplanted for aplastic complications of PNH. Four of these were from HLA‐identical siblings, and the patients were conditioned with cyclophosphamide. One graft was from a syngeneic twin without conditioning, and one from a two HLA‐antigen nonidentical father after conditioning with cyclophosphamide and total body irradiation. Three of the four recipients of allogeneic marrow developed acute and two chronic graft‐versus‐host disease (GVHD). Five of six transplanted for severe aplastic anemia are long‐term survivors with follow‐up ranging from more than 6.2 to more than 19.1 years. The HLA nonidentical transplant recipient experienced graft rejection and died of a pulmonary hemorrhage. Three patients were transplanted for nonaplastic complications of PNH consisting of life threatening recurrent thromboses or refractory hemolysis. Two of these patients received marrow grafts from HLA‐identical siblings after conditioning with busulfan and cyclophosphamide. They are surviving with normal hemograms >2.2 and >2.5 years and had mild chronic GVHD which resolved, although one has biochemical evidence of PNH in 15% of the red cells. One received a syngeneic marrow graft without conditioning but reverted to PNH. He is alive >8.6 years after transplantation. Marrow transplantation for aplastic complications of PNH is successful, well tolerated, and compatible with long‐term survival when an HLA‐identical sibling or a syngeneic donor is available. For patients without aplasia, one must weigh the complications of transplantation with the life threatening nature of thrombotic episodes and hemolysis. © 1992 Wiley‐Liss, Inc.
A new gene deletion involving the α2‐, α1 ‐, and 81‐globin genes in a black family with Hb H disease
Authors: Fei Y. J. , Liu J. C. , Walker E. L. D. , Huisman T. H. J.
Published: February 2007

A new deletion of ∽ 8.5 kb that includes the α2‐, α1‐, and θ1‐globin genes was detected in a father and newborn son of a black family from Georgia. In the newborn baby the chromosome with the deletion occurred together with a rightward (‐α3.7) deletion chromosome. The resulting Hb H disease was detected at birth by the high level of Hb Bart's; a moderate anemia with severe microcytosis and hypochromia was present at the age of 5 months. A review of cord blood testing results for a period of over 20 years, involving at least 200,000 black newborns, indicated that this baby was the first with a level of Hb Bart's in excess of 10‐15%; this underscores the rarity of α‐thalassemia‐1 in this population. © 1992 Wiley‐Liss, Inc.
Delivery of infants with Glanzmann thrombasthenia and subsequent blood transfusion requirements: A follow‐up of 39 patients
Authors: Awidi Abdalla S.
Published: February 2007

The delivery and transfusion requirements of 39 patients with Glanzmann thrombasthenia are described. Of these, type I thrombasthenia was found in 21 females and 12 males, and type II thrombasthenia was found in four females and two males. Eighteen of these patients were born in the hospital and 21 at home. All were delivered vaginally. Absence of excessive hemorrhagic symptoms was noted in neonates affected with thrombasthenia. The patients were followed for a total of 220 patient years and received a total of 276 units of blood during this period. In females, the dominant reason for transfusion was menorrhagia followed by gum bleeding and epistaxis, while in males epistaxis, gum bleeding, and circumcision accounted for most of the transfusions. © 1992 Wiley‐Liss, Inc.
Total sialic acid in human and canine platelets does not change with the platelet age
Authors: Mezzano Diego , Aranda Eduardo , García María Eugenia , Pereira Jaime , Quiroga Teresa , Pérez Marcos
Published: February 2007

Total platelet sialic acid (SA) was measured in three experimental conditions: (1) human and canine platelet density subpoputations obtained by centrifugation in arabinogalactan gradients, (2) circulating canine platelets during recovery from experimental immune and mechanical thrombocytopenias, and (3) platelets obtained from a patient with chronic immune thrombocytopenic purpura before and after splenectomy. The density of human and canine platelets is, in part, determined by their age. We found no significant differences in total SA between high‐density (HD) and low‐density (LD) platelets (9.32 ± 2.0 vs. 9.55 ± 1.3 μg/mg of platelet protein in dogs and 9.02 ± 2.3 vs. 9.10 ± 2.9 ng/mg in humans). In the human and canine thrombocytopenic models, the entrance of new platelets from the bone marrow is followed by their aging in the circulation. In these models, no significant changes in total SA content were detected in sequential measurements during the recovery of the thrombocytopenia. Accordingly, we conclude that total SA in human and canine platelets is unrelated to their age in circulation. These results do not support the notion that the loss of SA from membrane glycoproteins determines the recognition and removal of platelets from the circulation. © 1992 Wiley‐Liss, Inc.
Pulmonary leukostasis without hyperleukocytosis: A clinicopathologic study of 16 cases
Authors: Soares Fernando Augusto , Landell Glaucia A. Magnani , Cardoso Maria Camila de Miranda
Published: February 2007

Pulmonary leukostasis is a serious, almost always fatal, complication usually reported to occur in patients with acute granulocy tic leukemias when the peripheral white blood cells exceed 50,000/mm3. We report a Clinicopathologic study of 16 leukemic patients with pulmonary leukostasis and with < 50,000/mm3 circulating leukocytes. The results demonstrated that hyperleukocytosis per se cannot be the cause of pulmonary leukostasis, but that other factors, such as the presence of circulating blasts and the affinity of neoplastic cells for the pulmonary endothelium, may be related to the development of acute respiratory distress in patients with leukemia. © 1992 Wiley‐Liss, Inc.
Bone marrow necrosis in lymphoma studied by magnetic resonance imaging
Authors: Weissman David E. , Negendank William G. , Al‐Katib Ayad M. , Smith Mitchell R.
Published: February 2007

We used magnetic resonance imaging (MRI) to examine the extent of necrosis in the marrow space in three patients with iymphoma who had necrosis in bone marrow biopsies taken from the posterior iliac crest. Two of the patients had multiple focal lesions observed in the spine, pelvis, and femurs. These lesions had MRI characteristics of fluid‐filled necrosis within marrow or Iymphoma. The third patient exhibited a unique pattern of anatomically extensive marginated lesions otherwise typical of avascular necrosis of bone. These cases provide evidence that MRI can document the extent of necrosis within the marrow space and can differentiate two distinct patterns of necrosis. © 1992 Wiley‐Liss, Inc.
Relapsing polychondritis: A paraneoplastic syndrome associated with myelodysplastic syndromes
Authors: Van Besien Koen , Tricot Guido , Hoffman Ronald
Published: February 2007

We report an unusual case of a patient with a myelodysplastic syndrome associated with life threatening relapsing polychondritis. The improvement in symptoms attributable to the relapsing polychondritis during treatment of the hematologic disorder suggests that relapsing polychondritis is a paraneoptastic syndrome associated with myelodysplastic syndromes. © 1992 Wiley‐Liss, Inc.
Successful treatment of T‐γ lymphoproliferative disease with human‐recombinant granulocyte colony stimulating factor
Authors: Lang David F. , Rosenfeld C. S. , Diamond H. S. , Shadduck R. K. , Zeigler Z. R.
Published: February 2007

A trial of recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) was attempted in a male with agranulocytosis, infection, and T‐gamma lymphoproliferative disease (T‐γ‐LPD). During five days of rhG‐CSF (960 μg/day), the absolute neutrophil count (ANC) increased from 0.0 to 4.5 K/μI. There were no changes in eosinophil or lymphocyte counts. In addition, there was no toxicity. Bone marrow cytotoxic/suppressor cells (CD57+/CD8+) were elevated (21.9%) before and decreased to 10.6% (normal < 12%) following rhG‐CSF. By contrast, there was no change in activated T cells (CD3+DR+) or T cell gene rearrangements. These findings suggest rhG‐CSF can improve granulopoiesis in T‐γ‐LPD, possibly by altering T‐cell mediated marrow suppression. © 1992 Wiley‐Liss, Inc.
Protein C concentrate prevents peripartum thrombosis
Authors: Manco‐Johnson Marilyn , Nuss Rachelle
Published: February 2007

A protein C deficient woman, with a past history of recurrent thrombosis and purpura fulminans, was successfully treated with protein C concentrate in the peripartum period. © 1992 Wiley‐Liss, Inc.
Clinical relevance of immunological dissection in T‐ALL: A report on 20 cases with stem cell (CD7+, CD4‐, CD8‐, CD1‐) phenotype
Authors: Ferrara Felicetto , Cimino Renato , Antinolfi Iolanda , de Rosa Carlo , Mele Giuseppina , Mettivier Vincenzo , Fusco Caterina , Vecchio Luigi Del
Published: February 2007

In a prospective study on 44 cases of T‐cell origin acute lymphoblastic leukemia, 20 patients were found to display an immature immunophenotype (CD7+, CD4‐, CD8‐, CD1‐) and were classified as T‐stem cell leukemia (T‐SCL). Twenty‐four patients expressed CD4 and/or CD8 antigens on their blast cells, designated T acute lymphoblastic leukemia (T‐ALL). The T‐SCL subset showed a significantly higher median age, a more frequent incidence of extramedullary leukemia, a morphology L1 in most cases, and a poor response to treatment in terms of either complete remission rate or median survival duration. In addition, significant differences between the two groups were found in evaluating the number of days of blast disappearance from peripheral blood, of CR achievement, and of neutrophils and platelets recovery. We conclude that T‐SCL represents a distinct clinical entity, characterized by a poor response to ALL conventional chemotherapy. Alternative therapeutic approaches should be developed for patients suffering from this form of leukemia, to modify its severe prognosis. © 1992 Wiley‐Liss, Inc.