bluuebunny/crossref_metadata_2025 huggingface dataset:
Gray platelet syndrome in the elderly
Authors: Berrebi Alain , Klepfish Abraham , Varon David , Shtalrid Mordechai , Vorst Eliakim , Nir Emanuel , Lahav Judith
Published: February 2007

A 68‐year‐old male who suffered from thrombocytopenia and mild splenomegaly for 18 years was found to present agranular gray platelets on peripheral blood smear. Bone biopsy revealed a mild, diffuse, reticular fibrosis with no collagen, and electron microscopy of the platelets showed an absence of almost all the α‐granules. Platelet thrombospondin and fibronectin analysed by SDS‐polyacrylamide gel electrophoresis and Rocket immunoelectrophoresis were absent. Follow‐up of 4 years showed the same parameters with no evidence of active myeloproliferative or dysmyelopoietic disorders. Hemorrhagic diathesis was limited to ecchymoses and postprostatectomy bleeding, necessitating platelet transfusion. This led us to conclude that our patient probably had a constitutional primary α‐granule deficiency or gray platelet syndrome. This extremely rare defect has been described in less than 10 patients, all of them very young. Our observation shows that these patients may have a long, uneventful survival.
Recombinant interferon gamma in hairy cell leukemia, multiple myeloma, and Waldenstrom's macroglobulinemia
Authors: Quesada Jorge R. , Alexanian Raymond , Kurzrock Razelle , Barlogie Barthel , Saks Samuel , Gutterman Jordan U.
Published: February 2007

Fifteen patients with multiple myeloma, five with hairy cell leukemia, and five with Waldenstrom's macroglobulinemia were treated with recombinant interferon gamma (rINF‐gamma) to determine the antitumor activity of this agent. The rIFN‐gamma was administered by daily intramuscular injection at doses ranging from 0.125 to 0.5 mg/m2. No responses were observed in patients with multiple myeloma, although in one patient the disease has remained stable for over 16 months. Minimal improvement in some hematologic indexes were observed in three of five patients with hairy cell leukemia. One partial remission and one minor response were documented in two of the five patients with Waldenstrom's macroglobulinemia. In five patients, an increase in normal serum immunoglobulins was observed. These results suggest that there is only minimal activity of rIFN‐gamma as a single agent in neoplasms of B‐cell origin.
Acute lymphoblastic leukemia in a patient with longstanding polycythemia vera: Cytogenetic analysis reveals two distinct abnormal clones
Authors: Anastasi John , Pettenati Mark J. , Le Beau Michelle M. , Kwaan Hau C. , Weil Susan C.
Published: February 2007

A 68‐year‐old female patient is described in whom acute lymphoblastic leukemia followed a long course of polycythemia vera. Chromosomal analysis of a peripheral blood specimen at the time of blastic transformation revealed two distinct clones: one characterized by a chromosomal abnormality frequently noted in polycythemia vera and the other by a rearrangement characteristically observed in lymphoid malignancies. These findings suggest the existence of two independent hematologic diseases: this phenomenon would not support the speculation from previous reports that lymphoproliferative disorders in patients with polycythemia vera arise from clonal evolution.
Recurrent spontaneous bacterial peritonitis in a patient with polycythemia vera
Authors: Nagler Arnon , Hayek Tony , Brenner Benjamin , Eidelman Shmoel
Published: February 2007

Spontaneous bacterial peritonitis (SBP) is an infectious process that usually occurs in patients with cirrhosis. There are few reports of SBP in patients with other pathologies such as nephrotic syndrome, acute and chronic hepatitis, cardiac ascites, and ascites secondary to neoplastic disease. We report a patient with polycythemia vera in whom recurrent episodes of SBP occurred 8 months following a portacaval shunt operation for Budd‐Chiari syndrome. Conceivably, the polycythemia vera (PV) complicated by hepatic vein thrombosis and portacaval shunt resulted in significant loss of hepatic reticuloen‐dothelial system function and predisposed the patient to bacterial peritonitis.
Zinc status of children with sickle cell disease: Relationship to poor growth
Authors: Phebus Carol K. , Maciak Barbara J. , Gloninger Margaret F. , Paul Harbajan S.
Published: February 2007

We examined the zinc status of 80 children with sickle cell disease (SCD) and 44 disease‐free sibling controls aged 3 to 18 years. For both patients and controls, variations in serum zinc by age, type of hemoglobinopathy, and growth status were measured. The mean serum zinc concentration of patients was significantly lower than for controls (77.8 ± 9.9 vs. 82.2 ± 9.8 μg/dl, mean ± 1SD, P < .05). Serum levels of alkaline phosphatase (AP) and retinol‐binding protein (RBP), two zinc‐dependent proteins, were also lower among patients (AP: 171 ± 66 vs. 243 ± 97 IU/L, P < .001; RBP: 1.92 ± .9 vs. 2.77 ± .9 mg/dl, P <.001). Patients ≥ 12 years of age (n = 34) had significantly lower zinc levels than those < 12 years (74.5 ± 8.4 vs. 80.3 ± 10.3 μg/dl, P < .01), and children with homozygous SCD (Hb SS, n = 55) had a more pronounced deficiency than those with a variant hemoglobinopathy (76.3 ± 8.9 vs. 81.5 ± 11.5, μg/dl, P < .05). Patients classified as having “poor” growth (height‐for‐age < 5th percentile, n = 24) had a lower serum zinc level than those with “normal” growth (72.8 ± 8.0 vs. 79.8 ± 10.0 μg/dl, P < .01). Dietary intake data, body mass index, and serum total protein and albumin levels were similar for patients and controls, suggesting that zinc deficiency in SCD does not relate to inadequate dietary intake. The origin of low serum zinc levels in children with SCD is more likely to relate to factors such as increased urinary zinc excretion, chronic intravascular hemolysis, and/or zinc malabsorption.
Restriction of blood and marrow CLL‐B cells to free L‐chain IG secretion: Implication for normal B‐cell function and control
Authors: Hopper John E. , O'brien Jamie , Papagiannes Elaine
Published: February 2007

The culture supernatant immunoglobulin (CSIg) of blood mononuclear cells (MNCs) from 14 patients with chronic lymphocytic leukemia (CLL) was determined using a panel of. nanogram‐sensitive radioimmunoassays that measured IgM, IgG, IgA, total K‐lg, and total λ‐lg. Bone marrow cells from three patients were also cultured and the blood and marrow CSIg results were compared. The CSIg of 1‐day cultures was employed as a measure of shedded surface membrane lg (Smlg) for the 7‐ and 14‐day cultures. Adjusting for shedded Smlg, it was found that in resting unstimulated conditions, monotypic free light (L) chain was virtually the only identifiable secreted lg product in 12 of 14 blood MNC cultures and in three of three marrow cell cultures. In pokeweed mitogen (PWM)‐stimulated cultures, monotypic free L chain also dominated, except for significant polyclonal Ig secretion found in three cultures from residual normal blood MNCs. The secretion by CLL‐B cells of significant amounts of free L chain with a virtual absence of whole Ig raises important questions about the presence and function of phenotypically equivalent normal B cells in blood and bone marrow, and also the immunological role of secreted free L chain. Noting recent evidence that PWM‐stimulated normal blood MNCs secrete significant amounts of polyclonal free L chain, the argument is advanced that normal blood and bone marrow contain B cells of CLL‐B phenotype and that secreted free L‐chain‐bearing clonal idiotypic markers interact with autologous cells of the idiotypic regulatory network and possess a key role in the regulation of clonal growth and Ig synthesis.
Guidelines for clinical protocols for chronic lymphocytic leukemia: Recommendations of the national cancer institute‐sponsored working group
Authors: Cheson Bruce D. , Bennett John M. , Rai Kanti R. , Grever Michael R. , Kay Neil E. , Schiffer Charles A. , Oken Martin M. , Keating Michael J. , Boldt David H. , Kempin Sanford J. , Foon Kenneth A.
Published: February 2007

The National Cancer Institute (NCI)‐sponsored Chronic Lymphocytic Leukemia (CLL) Working Group was convened to develop a set of standardized eligibility, response, and toxicity criteria for clinical trials. We recognized the previous efforts in 1967 published again in 1973 as the report of the Chronic Leukemia‐Myeloma Task Force [1] and 1978 of Cancer and Leukemia Group B (CALGB) [2]. We have used these reports for guidance during the current effort. Several noteworthy developments in the past few years have made it necessary to modify the previous guidelines. First, the diagnostic criteria for CLL and its clinical staging have been developed and well defined. Second, although staging systems facilitated entry of comparable and relatively homogeneous groups of patients in clinical trials, the definitions of response (CR) and partial response (PR) were not uniformly adopted from the previous guidelines in the clinical trials (Tables IA, IB); therefore, comparisons of results obtained in different studies became difficult. Third, there has been an improvement in our understanding of the immunology and biology of CLL. Finally, we are witnessing the emergence of several chemotherapy agents that promise impressive activity in CLL (e.g., 2′‐deoxycoformycin [3], fludarabine monophos‐phate [4,5]), and thereby offer the potential for improving survival time in this disease. To best identify regimens worthy of continued pursuit in large comparative trials, standardized guidelines for evaluation are essential. A number of laboratory investigations are also presented for which scientific interest is high yet relevance remains to be determined; thus, they are presented as companion studies to the clinical trials. This mechanism allows for flexibility in the testing of these questions and for additional ideas in the future without requiring modification of an entire treatment protocol.
Transient bone marrow aplasia associated with non‐A, non‐B hepatitis
Authors: Dhingra Kapil , Michels Sheryl D. , Winton Elliott F. , Gordon David S.
Published: February 2007

We describe two patients who developed aplastic anemia early in the course of non‐A, non‐B hepatitis. Spontaneous rapid recovery of bone marrow function occurred in both patients. Although early bone marrow transplantation has been recommended as the treatment of choice in hepatitis‐associated aplastic anemia, these patients illustrate the need for a period of expectant observation before undertaking bone marrow transplantation in such patients.
Acyclovir in the treatment of aplastic anemia
Authors: Gómez‐Almaguer David , Marfil‐Rivera Javier , Kudish‐Wersh Alex
Published: February 2007

Eight patients with idiopathic severe aplastic anemia received acyclovir as the initial treatment to ascertain if this antiviral therapy could be effective. Three patients showed improvement, but only one had a sustained recovery. The responses could be coincidental, but it seems that some patients can benefit from acyclovir. More studies are needed on the role of viruses and antiviral therapy in relation to severe aplastic anemia.
Extensive bone marrow necrosis in patients with cancer and tumor necrosis factor activity in plasma
Authors: Knupp Charles , Pekala Phillip H. , Cornelius Peter
Published: February 2007

Tumor necrosis factor (TNF), a macrophage secretory protein produced by peripheral blood monocytes from patients with cancer, has been shown to possess cytotoxicity toward tumor cells in vitro. TNF in the blood of individuals with cancer is usually not detectable except with extremely sensitive radioimmunoassay or enzyme‐linked immunosorbent assay (ELISA) methods. We have encountered two patients with the rate syndrome of extensive bone marrow necrosis in association with cancer. The first patient presented with marrow failure secondary to necrosis and was found to have adenocarcinoma in thoracic lymph nodes, lung, and marrow lymphatics at autopsy. Plasma tested at two dilutions (1:200 and 1:2,000) contained TNF at a concentration of 8.3 ng/ml, or 80 U/ml by a cytotoxicity assay using LM cells. The presence of TNF was confirmed with immunoblotting. The second patient had a poorly differentiated lymphoid tumor involving bone marrow, pancytopenia, and marrow necrosis. The plasma cytotoxicity assay indicated the presence of 0.7 ng/ml or 7 U/ml TNF. TNF was not detectable in plasma from six other patients with untreated cancer involving bone or bone marrow using either of our methods. The levels of TNF in the two patients with marrow necrosis were greater than those previously measured by others in patients with cancer but were comparable to those noted in patients with lethal sepsis. Since large doses of TNF have been shown to cause organ necrosis in animals, the data presented here are consistent with TNF involvement in mediating the observed marrow necrosis in our patients.
High‐grade non‐Hodgkin lymphoma relapsing as low‐grade follicular lymphoma: So‐called downgraded lymphoma
Authors: Kerrigan Daniel P. , Foucar Kathy , Dressler Lynn
Published: February 2007

Evolution of low‐grade Non‐Hodgkin Lymphoma (NHL) into a more aggressive neoplasm is a common, well‐documented event in NHL. The reverse process, in which a less aggressive component becomes evident during the course of treatment for a highergrade NHL, has only recently been recognized. This lymphoma “downgrading” has been reported at the time of relapse in both radiation‐ and chemotherapy‐treated patients who initially presented with high‐ or intermediate‐grade lymphoma. The etiology of this unusual transformation has not yet been determined. We present the clinical, morphologic, immunologic, and flow‐cytometric features of a patient with diffuse immunoblastic lymphoma who achieved a complete response to chemotherapy and then relapsed with follicular small‐cleaved‐cell lymphoma 3 years later. Morphologic and immunophenotypic findings suggest that both immunoblasts and small cleaved cells were present in the initial biopsy. DNA content analysis of the initial and relapse biopsies suggests that the immunoblastic component was more susceptible than the small cleaved cells to the chemotherapy that the patient received. Successful eradication of the rapidly proliferating immunoblasts with survival of less rapidly proliferating small cleaved cells may account for the unusual histologic transformation seen in this case.
Malignant chronic lymphocytic leukemia B cells elaborate soluble factors that down‐regulate T cell and NK function
Authors: Burton Jack D. , Weitz Carol H. , Kay Neil E.
Published: February 2007

To determine if the frequently observed T celt and natural kitler dysfunction in B‐chronic lymphocytic leukemia might be related to the presence of large numbers of malignant B cells, we studied the effects of secretory or shed products of CLL B cells on normal (control) T cell and NK function. The cell‐free supernatants from CLL B cells cultured from 24 to 48 hr inhibited a variety of T cell functions including: PHA‐induced proliferation, PHA‐stimulated entry of T cells into the cell cycle, and PHA‐induced production of interleukin‐2. In addition, B‐CLL supernatants diminished control NK activity. Purified control B cells and other malignant cell lines produced little or no inhibitory activity toward these T cell or NK functions. The sera from these same B‐CLL patients diminished PHA‐induced interleukin‐2 production by control T cells. Initial molecular characterization of the inhibitory factor(s) revealed it to be of low molecular weight (< 5000 daltons) with loss of functional activity after treatment with neuraminidase. This suggested that this substance might be either a ganglioside or glycoprotein whose inhibitory activity depends on the presence of a sialic acid moiety. If CLL B celts are capable of secreting or shedding immunosuppressive factors), then alteration of this property may result in a more normal immune system for these patients.
Studies of the proliferation and differentiation of immature myeloid cells in vitro. II. Acute myelogenous leukemia
Authors: Wang Zique , Gao Xue Zhi , Preisler Harvey D.
Published: February 2007

Immature myeloid celts prepared from patients with AML were placed into suspension culture and studied over a 2‐week period. Cell numbers usually fell and viability was not well maintained. Some degree of differentiation was observed in most cultures. Considering these observations, together with those derived from parallel studies of immature CML cells, the data suggest that AML cells are more dependent than CML cells on environmental conditions for the maintenance of cell viability and proliferation. This is especially the case for AML cells obtained at the time of initial diagnosis. On the other hand, AML cells and myeloid blastic crisis CML cells are similar with respect to their apparent greater ability to differentiate in vitro than in vivo. The addition of recombinant hemopoietins to the suspension cultures of AML cells is associated with either increased proliferation or differentiation but not both. The cells of different patients respond differently to the different hemopoietins and the different hemopoietins produce different affects in cultures of cells obtained from the same patient.
Altered cytokine activities are related to the suppression of synthesis of normal immunoglobulin in multiple myeloma
Authors: Kawano Michio , Iwato Koji , Asaoku Hideki , Tanabe Osamu , Tanaka Hideo , Ishikawa Hideaki , Kuramoto Atsushi
Published: February 2007

The content of peripheral blood B cells (B1+) was reduced in patients of multiple myeloma (MM) and not in those with benign monoclonal gammopathy (BMG) compared to normal donors (P < 0.01). This observation correlated with the suppression of synthesis of normal immunoglobulin (Ig) in MM. Thus, cytokine activities regulating the proliferation of normal mature B cells, such as B cell stimulatory factor 1 (BSF‐1)/ inlerleukin 4 (IL‐4), B cell growth inhibitory factor (BIF) and IL‐2 in peripheral blood T cells, and IL‐1 in peripheral blood adherent cells, were investigated in patients with BMG (n ‐ 7) and MM (n = 28). All patients of MM having a marked suppression of synthesis of all other normal Ig, had significantly lower levels of BSF‐1 activity and inversely higher levels of BIF activity than those of normal donors. However, patients with BMG having no suppression of synthesis of normal Ig had BSF‐1 and BIF activities similar to normal donors. There was no significant difference in IL‐1 and fL‐2 activities between both normal donors and BMG versus MM patients. These data show that in MM altered cytokine activities correlate with suppression of synthesis of normal Ig.
Erythrocyte enzyme activities in myelodysplastic syndromes: Elevated pyruvate kinase activity
Authors: Tani Kenzaburo , Fujii Hisaichi , Takahashi Keisuke , Kodo Hideki , Asano Shigetaka , Takaku Fumimaro , Miwa Shiro
Published: February 2007

The erythrocyte enzyme activities in twenty‐six cases of myelodysplastic syndromes were determined. There were remarkably abnormal levels in seven cases; namely, four cases showed increased hexokinase activity, three cases showed increased pyruvate kinase activity, and two cases showed increased adenosine deaminase activity. Among these, one case with elevated pyruvate kinase activity showed the novel expression of M2‐type pyruvate kinase activity, in addition to the R‐type pyruvate kinase activity normally found in erythrocytes. Southern blotting of peripheral leucocyte DNA revealed only an amplified PK‐LR genome, which derived from the chromosomal abnormality of a 1;7 translocation. The mechanism responsible for switching M2‐type to R‐type during erythroid maturation was considered to be partially disrupted in this case.
Primary lymph node presentation of angiocentric lymphoma associated with features of a hemophagocytic syndrome
Authors: Kueck Brian D. , Hanson Curtis A. , Weissman David E. , Bayliss Katherine
Published: February 2007

The spectrum of post‐thymic T‐cell neoplasia includes the angiocentric immunoproliterative lesions, a group of disorders histologically exhibiting vascular infiltration and destruction; included among these disorders is angiocentric lymphoma. In contrast to the typical extranodal presentation seen in the angiocentric immunoproiiferative lesions, this report describes a case of angiocentric lymphoma presenting as primary lymph node disease with clinicopathologic findings mimicking a hemophagocytic syndrome. Rearrangement of the T‐cell receptor beta chain documents this case to be a clonal T‐cell neoplasm. The association of this distinct histologic type of T‐cell malignancy with hemophagocytic syndromes is reviewed.
Trephine needle bone marrow biopsy in the initial staging of Hodgkin disease: Sensitivity and specificity of the ann arbor staging procedure criteria
Authors: Ellis Mark E. , Diehl Louis F. , Granger Elder , Elson Edward
Published: February 2007

The purpose of this study was to test the value of the Ann Arbor staging procedures committee criteria in defining a group of newly diagnosed patients with Hodgkin disease who do not have involvement of the bone marrow and do not need this procedure performed. One hundred sixty‐six bilateral and 16 unilateral trephine bone marrow biopsies were performed in a consecutive series of 182 patients undergoing initial staging for Hodgkin disease. Bone marrow involvement was found in 13 patients. Advanced stage, defined as stage III or IV, occurring in 92%, anemia occurring in 100%, and “B” symptoms present in 100% were found to be the most sensitive indicators for bone marrow involvement. Osseous disease (99%), platelet count < 150,000/mm3 (98%), and WBC < 4,800/mm3 (94%) were the most specific parameters. The known association of bone marrow involvement with older patients, lymphocyte depleted histology, lower blood cell counts, anemia, advanced stage, and poorer survival is verified. The Ann Arbor staging procedures committee criteria for performing a bone marrow biopsy were shown to be 100% sensitive and 40% specific. Use of these criteria would have found all 13 patients with bone marrow involvement. Of the 73 patients who did not meet the criteria, no patient had bone marrow involvement. Use of the Ann Arbor staging procedures committee criteria is recommended.
Differential nucleolus organizer activity in normal and leukemic bone marrow
Authors: Arden K. C. , Johnston D. A. , Cork A. , Pathak S.
Published: February 2007

A cytochemical technique that uses silver nitrate staining has been used to study the nucleolus organizer activity in bone marrow cells from 13 patients with acute lymphocytic leukemia (ALL), 11 patients with chronic myelogenous leukemia (CML), 7 patients with acute myelogenous leukemia (AML), and 4 healthy persons. Our results indicate that the nucleolus organizer region (NOR) activity was significantly lower in the control group than in the ALL patients. The NOR activity level was significantly lower in both the CML patients in chronic phase and the AML patients than in the ALL group and similar to the control group. These disease‐related differences in NOR activity as detected by silver staining can be used as diagnostic procedure in evaluating human leukemias.
Coexistence of myelodysplastic syndrome and untreated chronic lymphocytic leukemia with development of acute myeloid leukemia immediately after treatment of chronic lymphocytic leukemia
Authors: Bracey Arthur W. , Maddox Anne‐Marie , Immken Ladonna , Hsu Su Ming , Marks Michael E.
Published: February 2007

A 72‐year‐old man originally seen for anemia and thrombocytopenia was determined to have chronic lymphocytic leukemia (CLL). Bone marrow examination at the time of CLL diagnosis revealed a small but significant population of atypical blasts. Cytogenetic analysis of the bone marrow aspirate disclosed chromosomal abnormalities (‐7, +8) suggestive of a myelodysplastic syndrome. Shortly after treatment of the CLL, there was proliferation of the previously noted blast population, which cytochemical studies demonstrated to be of the myeloid series thus indicating acute myeloid leukemia superimposed on CLL. This report presents microscopic, cytogenetic, immunophenotypic, and cytochemical evidence to document the evolution of acute myeloid leukemia in the bone marrow of a patient with CLL after one course of chemotherapy.
Platelet survival and turnover: Important factors in predicting response to splenectomy in immune thrombocytopenic purpura
Authors: Siegel Robert S. , Rae Janice L. , Barth Susan , Coleman R. Edward , Reba Richard C. , Kurlander Roger , Rosse Wendell F.
Published: February 2007

Autologous indium‐111 platelet sequestration and survival studies were performed on 59 immune thrombocytopenic purpura (ITP) patients, 21 of whom underwent splenectomy shortly thereafter. Sequestration patterns were primarily splenic in 46 patients, primarily hepatic in 6 patients, and both splenic and hepatic in 8 patients. The mean platelet survival ranged from 15 to 211 hr (normal, 180‐220 hr), and mean platelet turnover (a measure of platelet production rate) varied from 99 platelets/μl/hr to 7,585 platelets/μl/hr (normal 1,200‐1,600 platelets/μl/hr). Among splenectomy patients, 13 had an excellent response, and 8 had a fair or poor response. Neither the pattern of platelet sequestration nor the quantity of platelet‐associated IgG was useful in predicting response to splenectomy. There was, however, a striking correlation between platelet studies showing short survival/high turnover and subsequent excellent responses to splenectomy. Conversely, patients with only moderately decreased survival and low turnover had an unpredictable response to splenectomy. This investigation demonstrates that ITP patients are a heterogeneous population and include a significant subset whose thrombocytopenia results primarily from decreased turnover. Platelet kinetic studies appear useful in predicting beneficial response to splenectomy.
Comparison of laboratory tests used for identification of the lupus anticoagulant
Authors: Lo Samuel C. L. , Oldmeadow Michael J. , Howard Margaret A. , Firkin Barry G.
Published: February 2007

A comparison of the sensitivities of the ten most commonly used tests for the identification of the lupus anticoagulant (LA) and the lupus cofactor phenomenon was undertaken on 18 patients. All investigations, except the cardiolipin‐antibody ELISA assay, were carried out using patient's plasma alone followed by a 1:1 mix with control plasma. Dilution studies (1:3, 1:6, 1:9—patient:control) were also carried out. The kaolin clotting time (KCT) was the only test positive in all patients at all dilutions, while the dilute activated partial thromboplastin time with kaolin (Dil‐APTT) registered 17 of 18 positive at all dilutions. Both the dilute Russell viper venom time (Dil‐RVVT) and the tissue thromboplastin inhibition time (TTI) (1/500 thromboplastin) identified the LA in 17 of 18 patients on initial testing but were less sensitive in the dilution studies. The KCT is not a suitable test for routine laboratory use, as it requires an individual filtration step. Therefore a combination of either the Dil‐APTT or Dil‐RVVT together with the TTI (1/500 dilution thromboplastin) is recommended for routine LA screening, as all patients with LA in this study were identified using these easily automated tests. The lupus cofactor phenomenon was most frequently demonstrated using the Dil‐APTT.
8;21 translocation in myelodysplasia secondary to essential thrombocythemia
Authors: Knottenbelt Elaine , Hallett Janet , Jacobs Peter
Published: February 2007

A case is presented of a 73‐year‐old woman who received busulphan for essential thrombocythemia and subsequently developed a myelodysplastic syndrome (MDS), which transformed to acute nonlymphoblastic leukaemia within 1 month. Cytogenetic studies showed a 46,XX,t(8;21) (q22;q22) karyotype in all metaphases examined at diagnosis. The karyotypic abnormality is previously unreported in secondary myelodysplasia and may have specific clinical implications in this setting, such as early transformation to acute leukaemia and short survival. This finding contrasts with the generally favourable prognosis of the 8;21 translocation in patients with de novo acute nonlymphoblastic leukemia. A possible explanation for this difference may be the involvement of a committed progenitor in acute nonlymphoblastic leukaemia, while in myelodysplasia the more primitive multipotent stem cell may be affected.
Thrombocytopenia associated with auranofin therapy: Evidence for a gold‐dependent immunologic mechanism
Authors: Kosty Michael P. , Hench P. Kahler , Tani Patricia , McMillan Robert
Published: February 2007

Thrombocytopenia associated with gold therapy is thought to be due to an immunemediated mechanism. Relatively few patients have been studied so far, and precise details of the pathophysiology of this disease remain undetermined. We report a patient with gold‐induced thrombocytopenia resulting from auranofin therapy. The patient's plasma contained platelet‐reactive antibodies detectable only in the presence of gold salts. Antibody binding occurred at gold concentrations ranging from 0.01 to 10,000 ng/ml. The binding occurred independently of gold salt used, suggesting that substitution of a different gold preparation in this patient would result in a similar thrombocytopenia. These data support a drug‐dependent immune mechanism for platelet destruction.
Vasculitis in hairy cell leukemia: Rapid response to interferon alpha
Authors: Gómez‐Almaguer David , Herrera‐Garza José Luis , Garcia‐Guajardo Blanca M. , Garcia‐Taboada Blanca E.
Published: February 2007

A patient with hairy cell leukemia (HCL) and vasculitis was treated only with interferon alpha‐2b. A good, rapid response was obtained without using corticosteroids or immunosuppressors. Interferon may prove to be useful for the systemic therapy of patients with vasculitis associated with HCL.
Different sensitivities of rat and human red cells to exogenous Ca2+
Authors: Swislocki Norbert I. , Tierney Joan M.
Published: February 2007

During an examination of the effects of shear and of the Ca2+ ionophore A23187 on Ca2+ entry into erythrocytes of rats and humans, we noted that rat erythrocytes were much more sensitive to Ca2+‐induced hemolysis than the human cells. An examination of the effect of Ca2+ on transglutaminase, a cytosolic enzyme in the erythrocyte which crosslinks membrane proteins and renders cells less deformable, demonstrated a correlation between enzyme activity and Ca2+‐induced hemolysis. Both rat and human cells subjected to shear‐induced Ca2+ entry exhibited increased enzyme activity and altered membrane protein SDS‐PAGE patterns. Twenty micromolar A23187 with Ca2+ at concentrations above 80 μM caused hemolysis of rat erythrocytes. In contrast to human erythrocytes, under these conditions no membranes were recoverable from rat erythrocytes. At lower concentrations of Ca2+ (25 and 50 μM), however, rat erythrocytes maintained integrity, and exhibited enhanced transglutaminase activity and cross‐linking of membrane proteins. The rat enzyme can be activated 30% by 10 μM Ca2+, while 50 μM Ca2+ was necessary to achieve a similar activation of the enzyme from human red blood cells. In studies of shear‐stimulated Ca2+ uptake by erythrocytes the rat red cell enzyme was more readily activated. The SDS‐PAGE pattern of rat red cell membranes after a 30 sec shear showed specific changes in protein banding, including the appearance of bands >330 kDa. Changes in protein banding were also apparent in cytosolic proteins. This work supports the view that shear‐induced Ca2+ entry activates transglutaminase that leads to cross‐linking of membrane components, a loss of cell integrity, and eventual cell death.
Iron metabolism in normal and hemochromatotic macrophages
Authors: Baynes Roy D. , Bukofzer Gail , Bothwell Thomas H. , Meyer Theo E. , Friedman Brian M. , Macfarlane Bruce J. , Lamparelli Rosario D.
Published: February 2007

Certain metabolic pathways of iron were studied in macrophages (cultured human monocytes) obtained from normal and hemochromatotic subjects. The relative abilities of the hydrophobic ferrous chelator 2,2′ bipyridine and the hydrophilic ferric chelators desferrioxamine (DFO) and diethylenetriaminepenta‐acetic acid (DTPA) to release iron from normal and hemochromatotic macrophages which had previously been loaded with diferric transferrin were tested but there were no differences between the two groups. The relative affinity of the macrophages for diferric transferrin was next studied. Although the hemochromatic macrophages had a somewhat lower affinity for diferric transferrin iron than normal macrophages (Kd 4.7 × 10−8 M vs. 3.0 × 10−8 M) the difference did not reach statistical significance (t = 2.01013; P < 0.07). In a further experiment there was no evidence that apotransferrin was directly involved in the release of iron from hemochromatotic macrophages. A clue to the nature of postendocytotic trans‐membrane transport of iron was provided by the finding that it was inhibited by the hydrophobic ferrous chelator 2,2′ bipyridine. However, the degree of inhibition was similar in both normal and hemochromatotic macrophages. In summary, none of the metabolic processes examined in the present study was abnormal in cultured human blood monocytes from hemochromatotic subjects.
Subcutaneous desmopressin (DDAVP) shortens the bleeding time in uremia
Authors: Vigano Gian Luigi , Mannucci Pier Mannuccio , Lattuada Antonella , Harris Alan , Remuzzi Giuseppe
Published: February 2007

The intravenous infusion of 1‐deamino‐8‐D‐arginine vasopressin (DDAVP) is used as a nontransfusional form of treatment in patients with congenital and acquired bleeding disorders, including patients with uremia associated with prolonged bleeding times. Since uremic patients experience minor bleeding episodes that might be self‐managed at home (particularly epistaxis, gingival bleeding, and menorrhagia), we carried out a double‐blind, placebo‐controlled crossover study in nine uremics to evaluate whether the prolonged bleeding times could be shortened by subcutaneous injections of DDAVP. One hour after administration, the bleeding time was significantly shortened (P < .01) and became normal in seven of nine patients. After 4 hr, the bleeding time was still shorter than baseline (P < .01), but in only three patients was it still normal. There was no significant bleeding time change after placebo. When the same patients were treated with the same dose of DDAVP infused intravenously, the bleeding times were not significantly different from those measured after subcutaneous administration. Hence, subcutaneous DDAVP is an alternative method for short‐term shortening of the bleeding time in uremia, at least as effective as intravenous DDAVP but with the possibility of self‐administration by the patients at home.
Corticosteroid‐responsive pure red cell aplasia in rheumatoid arthritis and its association with pregnancy: A case report
Authors: Banavali S. D. , Parikh P. M. , Charak B. S. , Agarwala S. , Modi A. , Iyer R. , Saikia T. , Gopal R. , Advani S. H.
Published: February 2007

Pure red cell aplasia (PRCA) often occurs secondary to drug therapy for rheumatoid arthritis (RA). However, idiopathic PRCA in RA is very rare. Though different immunosuppressive therapies have been tried in the past with variable responses, there has been no case report in adults of favourable response to corticosteroids alone. We report a rare case of PRCA in RA, which responded to steroid therapy. Subsequently, the patient relapsed twice, during the first trimester of consecutive pregnancies. The association of PRCA with RA and pregnancy is discussed.
Suppression by bone marrow but not by blood T lymphocytes of autologous and allogeneic granulocytic stem cells in a case of lymphoproliferative T‐cell syndrome
Authors: Marinof Christine , Clément Serge
Published: February 2007

The bone marrow T lymphocytes of a patient suffering from a lymphoproliferative T‐cell syndrome suppressed the in vitro growth of autologous and allogeneic CFU‐GM. The patient's blood T lymphocytes had no suppressor effect on these same stem cells.
Granulocyte transfusion therapy and amphotericin B: Adverse reactions?
Authors: Dutcher Janice P. , Kendall Joyce , Norris Dottie , Schiffer Charles , Aisner Joseph , Wiernik Peter H.
Published: February 2007

One hundred twenty‐five granulocyte transfusions were given concurrently with amphotericin B to 31 granulocytopenic patients with acute leukemia during a four year period. Twenty‐six patients had culture‐documented, and 5 had presumed fungal infections; pulmonary infiltrates were present in 26 patient courses. Eight patients developed pulmonary deterioration temporally related to therapy with amphotericin, granulocyte transfusions, or both. One event occurred following amphotericin alone. Three additional reactions occurred in alloimmunized patients with antibodies to human leukocyte antigens (HLA) who received random donor granulocytes, which may indicate a potential mechanism for the pulmonary reactions. Two reactions potentially represent an adverse interaction between amphotericin and granulocytes, but these were reversible and were not unlike reactions expected with each modality alone. Our data fail to document a specific detrimental interaction between granulocyte transfusions and amphotericin beyond the reactions associated with each modality, and the data suggest that other clinical factors, particularly infection and alloimmunization, also contribute to pulmonary decompensation. We nevertheless recommend great care and attention be given to administering these modalities in the setting of severely ill patients.
Modified osmotic fragility test for the laboratory diagnosis of hereditary spherocytosis
Authors: Judkiewicz Luba , Bartosz Grzegorz , Oplatowska Anna , Szczepanek Andrzej
Published: February 2007

A modified osmotic fragility test, based on measurement of hemolysis in four hypotonic NaCl solutions and logarithmic linearization of osmotic fragility curve is, like the “Pink test,” a specific and sensitive test for the laboratory diagnosis of hereditary spherocytosis.
Further studies on the use of serum gastrin levels in assessing the significance of low serum B12 levels
Authors: Miller A. , Slingerland D. W. , Cardarelli J. , Burrows B. A.
Published: February 2007

The reported incidence of low serum vitamin B12 levels in patients ranges from 4% to 8%. In only a small percentage can this be ascribed to readily diagnosed pernicious anemia, malabsorption syndrome, or to gastrointestinal surgery. This leaves a number of patients in whom the meaning of the low serum B12 is not immediately apparent. In 71 patients with intact gastrointestinal tracts, hematological indices did not adequately separate patients with decreased absorption of unbound B12 from those with normal absorption. A low absorption of B12, either unbound or food‐bound, was found, however, when the level of serum gastrin was elevated. In contrast, a normal absorption of unbound B12 was likely (95% of 44 patients) when the serum gastrin was normal.
Successful treatment of severe refractory aplastic anemia with 3‐β etiocholanolone and nandrolone decanoate
Authors: Seewald T. R. , Zeigler Z. R. , Gardner F. H.
Published: February 2007

A patient with aplastic anemia, who had been unresponsive to androgens, antithymocyte globulin, high‐dose methylprednisolone, and cyclosporine, responded to treatment with 3‐β‐etiocholanolone, nandrolone decanoate, and prednisolone acetate. Six months following intiation of therapy, she became red cell and platelet transfusion independent with neutrophils persistently over 1,000/μl. A sustained partial remission has persisted for over 2 years. This observation suggests that a combined hematostimulatory approach may be of benefit, even in patients with long‐standing refractory aplasia.
Erythrocyte pyruvate kinase deficiency: A kinetic method for differentiation between heterozygosity and compound‐heterozygosity
Authors: Lakomek Max , Winkler Heinz , Linne Sabine , Schröter Werner
Published: February 2007

The goal of the present study was to search for criteria that allow one to distinguish between normal individuals and heterozygotes as well as compound heterozygotes for pyruvate kinase (PK) deficiency. As the residual activity of PK with heterozygotes was between 35% and 110% of the normal activity, it was necessary to find other methods to prove heterozygosity. The PK in the hemolysates of 23 patients suffering from PK deficiency, 36 paternal and maternal enzymes as well as the enzymes of five heterozygous and four normal siblings together with those of 20 normal individuals, were studied according to the recommendations of the International Committee for Standardization in Haematology. The following hematological and enzyme kinetic parameters can serve to identify heterozygotes for PK deficiency: 1) a slight reticulocytosis, 2) an up‐to‐twofold increase of the intracellular concentrations of glucose‐6‐phosphate in the erythrocyte, 3) a mixed cooperativity of the phosphoenolpyruvate (PEP)‐binding process of PK, 4) a decreased nucleotide specificity with guanosine diphosphate and uridine diphosphate, and 5) a lowered affinity for adenosine diphosphate. The most significant criterium found with all heterozygotes was a mixed cooperativity of the PEP‐binding process caused by the presence of a mixture of normal and mutant PK.
Heterogeneity in the breakpoints of chromosome 19 among acute leukemia patients with the t(11;19)(q23;p13) translocation
Authors: Mitani Kinuko , Sato Yuko , Kobayashi Yukio , Shibasaki Yoshikazu , Kasuga Masato , Inaba Toshiya , Hayashi Yasuhide , Miura Yasusada , Miyazono Kohei , Hirai Hisamaru , Urabe Akio , Takaku Fumimaro
Published: February 2007

Gene probes for insulin receptor (INSR) and c‐ets‐1 were hybridized to metaphase cells from three leukemic patients with the t(11;19)(q23;p13) translocation. Patients 1 and 2 were diagnosed as acute lymphocytic leukemia (ALL) (L2), and patient 3, as acute myelogenous leukemia (AML) (M4). The c‐ets‐1 gene was demonstrated to have translocated from chromosome 11 to the short arm of the rearranged chromosome 19 (19p+) in all three patients. On the other hand, the INSR gene translocated from chromosome 19 to the rearranged chromosome 11 (11q‐) in the AML case, but remained on the rearranged chromosome 19 in the two ALL cases. Thus, the breakpoints of chromosome 19 are different among the patients studied, proximal to the INSR gene locus in the AML case and distal in the two ALL cases. Consequently, the c‐ets‐1 gene and the INSR gene remain separated in the AML case, whereas they become close to each other in the two ALL cases. Rearrangement of these two genes was studied in the two ALL patients, with no positive data being obtained. The results suggest that there may be heterogeneity in the breakpoints of chromosome 19 among the t(11;19)‐associated acute leukemias.
Urokinase therapy for a central venous catheter thrombus
Authors: Suarez Carlos R. , Ow E. Phillip , Lambert George H. , Anderson Craig L. , Purewal Navtej S.
Published: February 2007

A 670 g premature infant is described in whom an intracardiac thrombus was documented. This thrombus formation probably resulted as a complication of an indwelling right atrial catheter. Thrombolytic therapy with urokinase was instituted, resulting in total and rapid dissolution. No hemorrhagic complications resulted. We believe that this particular thrombolytic therapy is safe and effective and should be considered when facing this particular complication.
The use of continuous infusion of factor concentrates in the treatment of hemophilia
Authors: Bona Robert D. , Weinstein Ralph A. , Weisman Steven J. , Bartolomeo Ann , Rickles Frederick R.
Published: February 2007

Bolus Infusion of clotting factor concentrates remains the most common approach to the treatment or prevention of bleeding in patients with hemophilia. Although successful use of continuous infusion of such concentrates has been reported by several groups, this alternative treatment method has not achieved widespread popularity. We report here our experience in one hemophilia center with the use of continuous infusion of factor VIII and factor IX concentrates in 13 patients, 11 with hemophilia A, and 2 with hemophilia B. All patients were treated successfully for bleeding episodes (e.g., hemarthroses, intracranial, or gastrointestinal bleeding) or for surgical procedures (appendectomy, thoracotomy, etc.). Three patients with low titer factor VIII inhibitors were treated successfully with constant infusion therapy, requiring a mean dose of factor VIII concentrate 2.3 fold (8.20 u/kg/h) higher than that of the patients without inhibitors (3.63 u/kg/h) to maintain a circulating plasma level of factor VIII of 1 u/ml.

The use of constant infusion of clotting factor concentrates is safe, efficacious, and more convenient than bolus therapy of factor concentrates and should be considered for hospitalized hemophilia patients requiring replacement therapy.
DNA rearrangement and restriction fragment length polymorphism within the first BCR intron in philadelphia‐positive acute leukemia
Authors: Nakamura Yuichi , Miura Osamu , Sugahara Yuichi , Maseki Nobuo , Kaneko Yasuhiko , Aoki Nobuo
Published: February 2007

In some patients with Philadelphia (Ph)‐chromosome positive acute lymphoblastic leukemias, breakpoints on chromosome 22 are reported to occur within the first BCR intron. To analyze the breakpoints in chromosome 22 of Ph‐positive acute leukemia patients without rearrangement of the 5.8 kb bcr, we cloned the 3′ part of the first BCR intron using a synthetic DNA probe. During the course of study, we mapped the region of the deletion/insertion of 1 kb that causes a restriction fragment length polymorphism (RFLP) and found a racial difference in the frequencies of the alleles giving rise to this RFLP. Analyses of the patients' samples indicated that breakpoints were located within the 8.5 kb EcoRI fragment of the first BCR intron in two of five Ph‐positive acute leukemia patients. The data, together with the previous reports, indicate that breakpoints within this ∼50 kb intron are widely scattered, in contrast to those confined within the 5.8 kb bcr in chronic myelogenous leukemias.
Thrombin and plasmin generation in patients with liver disease
Authors: Takahashi Hoyu , Tatewaki Wataru , Wada Ken , Yoshikawa Akira
Published: February 2007

Patients with liver disease frequently have multiple hemostatic abnormalities. Coagulation and fibrinolytic factors and inhibitors may decrease as the result of impaired synthesis and/or enhanced catabolism. In order to assess the actual degree of activation of coagulation and fibrinolytic systems in liver disease, plasma levels of thrombin‐antithrombin III complex (TAT) and plasmin‐α2‐antiplasmin complex (PAP) were measured together with cross‐linked fibrin derivatives (XDP), tissue‐type plasminogen activator (t‐PA), and plasminogen activator inhibitor (PAI‐1) in 31 patients with liver disease (five patients with acute hepatitis, seven with chronic hepatitis, nine with liver cirrhosis, and ten with hepatocellular carcinoma). Mean plasma levels of TAT (mean 4.2 ± SD 4.0 μg/L), PAP (0.7 ± 0.7 mg/L), and XDP (374 ± 518 μg/L) were significantly elevated in patients with liver disease as compared with normal subjects (TAT of 1.7 ± 0.3 μg/L, PAP of 0.2 ± 0.1 mg/L, and XDP of 30 ± 14 μg/L; P < 0.005). Plasma concentrations of t‐PA and PAI‐1 antigens were also elevated. When plotted by the disease categories, the magnitude of elevations of these parameters was variable among subgroups. Patients with acute hepatitis had considerably higher TAT levels. The mean PAP values were relatively high in chronic hepatitis and hepatocellular carcinoma, in which an elevation of the t‐PA/PAI‐1 ratio was observed. Although clearance of TAT and PAP should be evaluated in the future, these findings suggest that excessive amounts of thrombin and plasmin are actually generated in patients with liver disease.