bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital factor XIII deficiency associated with von willebrand disease
Authors: Grand B. , Blanco A. , Riveros D. , Ventura A. , Maugeri N. , Woods A. , Lazzari M.
Published: February 2007

A boy with umbilical bleeding and severe hemorrhages after minor trauma, without family bleeding history, was studied. Coagulation tests showed abnormalities in FXIII subunits and FVIII/vWF complex. Both parents presented results compatible with a heterozygote state for FXIII deficiency and the father had abnormalities of FVIII/vWF. The propositus was diagnosed as congenital FXIII deficiency associated with vWD. No severe hemorrhagic complication was observed after a prophylactic regimen with cryoprecipitates.
Acute myocardial infarction, non‐bacterial thrombotic endocarditis, and disseminated intravascular coagulation in a severe hemophiliac
Authors: Green David , Snapper Howard , Abu‐Jawdeh Graziella , Reddy Janardan
Published: February 2007

Thrombosis in hemophilia is very rare and is usually associated with the administration of prothrombin complex concentrates. We describe a severe hemophiliac with P. carinii pneumonia who had clinical and laboratory evidence of acute myocardial infarction and disseminated intravascular coagulation, and at autopsy, nonbacterial thrombotic endocarditis as well. We suggest that prothrombin complex concentrates should be used cautiously in the setting of acute infection, and perhaps be given with appropriate doses of anticoagulants such as heparin.
Ph chromosome in a patient with non‐leukemic non‐hodgkin B‐cell lymphoma
Authors: Fujii Hiroshi , Yashige Hiromi , Misawa Shinichi , Tanaka Shinji , Urata Yohji , Matuyama Fumio
Published: February 2007

A standard Philadelphia translocation, t(9;22) (q34;q11), was found in lymph node cells from a patient with non‐leukemic non‐Hodgkin lymphoma at the time of diagnosis. The rearrangement of the breakpoint cluster region (bcr) was not detected with a bcr‐3′ probe. The neoplastic clone was of monoclonal B‐cell character with E‐, CD5‐, CD10‐, CD13‐, CD19+, CD20+, CD21+, CD25‐, HLA DR+, and positive surface lg(kappa). The patient showed no evidence of chronic myelogenous leukemia.
The size and number of bone marrow megakaryocytes in malignant lymphoma and their relationship to abnormalities in platelet count
Authors: Gladwin A. M. , Martin J. F. , Trowbridge E. A. , Slater D. N. , Reardon D.
Published: February 2007

Platelet counts were measured routinely in 718 volunteer blood donors and 124 patients with malignant lymphoma. When considered by gender, the mean platelet counts of the patients with malignant lymphoma were significantly increased when compared to controls (P < 0.01). In addition, 9% of males and 4% of females with lymphoma exhibited a thrombocytosis, in which their platelet counts exceeded the upper limit of the normal platelet count for control subjects (defined as 2 SDs in excess of the mean value). Megakaryocyte whole size, cytoplasmic and nuclear sizes, and megakaryocyte numbers were also quantified in bone marrow obtained from the iliac crest of 5 hematologically normal subjects and 26 patients with malignant lymphoma. Mean megakaryocyte sizes were significantly greater in subjects with lymphoma, when compared to control values (P < 0.05). No significant differences in megakaryocyte numbers in bone marrow were observed between the two groups. For subjects with malignant lymphoma, platelet count was found to be significantly positively correlated with megakaryocyte size. The results of this study suggest that the elevated platelet count associated with malignant lymphoma is mediated by an increase in the size of the megakaryocytes in the bone marrow.
Absence of natural killer cells in a child with pure red blood cell aplasia
Authors: Abrahamov Ayala , Schlesinger Michael
Published: February 2007

A 16‐year old boy was known to suffer from red blood cell (RBC) aplasia from the age of 4 years. Peripheral blood lymphocytes (PBL) from the patient were found to lack natural killer (NK) cytotoxic activity, even after stimulation with α‐interferon. His PBL also lacked Leu‐7+ and Leu‐11+ cells, although his granulocytes showed normal expression of the Leu‐11 marker. The lack of NK cells did not seem to result from the various immunosuppressive treatments he received, since the NK deficiency was noted 2 years after he stopped receiving such treatment. The possibility is discussed that lack of NK cells may lead to the development of RBS aplasia if NK cells play a role in promoting the production of RBC.
G‐CSF enhanced granulocyte production in a child with severe neutropenia in the setting of fatal virus‐associated hemophagocytic syndrome
Authors: Azuma Eiichi , Tabata Nobutada , Shibata Takeo , Komada Yoshihiro , Ito Masahiro , Sakurai Minoru , Atsumi Shin‐Ichiro , Kawasaki Yoko , Ishii Masahiko
Published: February 2007

A 14‐year‐old boy with fatal varicella zoster virus‐associated hemophagocytic syndrome (VAHS) was treated with recombinant human granulocyte colony‐stimulating factor (G‐CSF) based on the finding that the patient had severe neutropenia and possible bacterial superinfection. Support for the G‐CSF therapy in VAHS is provided by the recent reports that G‐CSF is relatively specific for the granulocyte lineage; it would not activate mature monocyte/macrophage/histiocyte lineage in VAHS, where the most striking morphologic feature is histiocytic hyperplasia with hemophagocytosis. He responded well to G‐CSF with an elevation of neutrophil counts. There were no effects on other blood cells. The result indicates that G‐CSF is useful to increase granulocyte production in severe neutropenia, even in the setting of fatal VAHS.
Protein S and C alterations in acutely III patients
Authors: Sheth S. B. , Carvalho A. C.
Published: February 2007

Protein C, a potent vitamin K‐dependent protein activated by an endothelial cell cofactor, thrombomodulin, has anticoagulant and profibrinolytic activity. Free protein S, a cofactor for protein C, potentiates protein C activity at the endothelial cell surface. Pulmonary thromboemboli are a consistent finding in adult respiratory distress syndrome (ARDS). To determine if protein S or protein C were affected by widespread endothelial cell damage in ARDS, we measured bound and free protein S levels and protein C antigenic and functional levels in 18 patients with acute lung injury, 6 critically ill patients without lung history, and 22 normal subjects. Free (PS:F) and bound (PS:Ag) protein S and protein C antigen (PC:Ag) levels were measured using an enzyme‐linked immunoassay and protein C function (PC:Fn) by measuring its anticoagulant activity. We found a significant decrease in bound and free protein S levels of both patient groups in comparison to normal and a shift toward the inactive, bound protein S form. In addition, a significant decrease in free protein S compared to bound protein S in both patient groups was observed. While both PC:Ag and PC:Fn were significantly reduced compared to normal, the PC:Fn was significantly and severely decreased out of proportion to the PC:Ag in both patient groups. There was no difference between those with and without lung injury for both protein S and protein C. Analyzed according to etiology of lung injury, there was no difference in the bound and free protein S, nor in PC:Ag and PC:Fn levels between patients with sepsis and trauma. However, there were significant decreases in both protein S and protein C levels compared with normal subjects. Levels of both PS and PC levels in patients who survived did not differ from those who died. In summary, our data show that both protein S and C are markedly deranged in acutely ill patients who suffered from either sepsis or trauma, and these changes are independent of lung injury. The marked reductions in functional activity of PS and PC may be contributing factors to the thromboembolic complications often observed in these patients.
Effective therapy of human immunodeficiency virus‐associated anemia with recombinant human erythropoietin despite high endogenous erythropoietin
Authors: Dacosta Noshir A. , Hultin Mae B.
Published: February 2007

A 32‐year‐old woman with human immunodeficiency virus (HIV) infection and progressive anemia presented to University Hospital with a hemoglobin of 3.4 g/dl. Because of her religious beliefs, she refused transfusion, and no iron or vitamin deficiency was found. She responded to recombinant human erythropoietin 150 U/kg intramuscularly thrice weekly with a rise in hemoglobin to 9.3 g/dl by 3 months of treatment. The serum erythropoietin level before treatment was markedly elevated at 1,340 mU/ml.
Modulation of tissue plasminogen activator biosynthesis by phosphatidylinositol liposomes in human fetal lung fibroblasts
Authors: Floru S. , Gelvan A. , Maran R. , Kadouri A. , Cohen A. M.
Published: February 2007

Phosphatidylinositol (PI) liposomes at 40 μM increased tissue plasminogen activator (t‐PA) biosynthesis by human fetal lung fibroblasts IMR‐90 (FLF), after 5 days of incubation by 7.4 ± 1.4 times of the control level. Other phospholipid liposomes, such as phosphatidylserine (PS), phosphatidylcholine (PC), and phosphatidylglycerol (PG), had no effect on t‐PA biosynthesis by FLF. The induction of t‐PA biosynthesis by PI liposomes was inhibited by specific inhibitors of phosphoinositide pathway: gentamycin and lithium chloride. Thus, gentamycin inhibited the effect of PI liposomes on t‐PA biosynthesis by 76% (P < 0.001), while it had no effect on control FLF. Likewise, lithium chloride inhibited t‐PA biosynthesis of both PI‐treated and control FLF by >84%. The induction of t‐PA biosynthesis by PI liposomes was dependent on RNA transcription and independent of DNA biosynthesis.
Danazol therapy for cyclic thrombocytopenia
Authors: Rocha Rafael , Horstman Lawrence , Ahn Yeon S. , Mylvaganam Ravindra , Harrington William J.
Published: February 2007

Cyclic thrombocytopenia is a rare disease characterized by cyclic oscillations of platelet counts from very low to normal or higher. Severe hemorrhage may occur during the thrombocytopenic phase. To date, treatments for this disorder have been disappointing. Its pathophysiology is unknown. We report a successful outcome using danazol therapy.

It can be argued that the long‐term outcome was due to spontaneous remission. However, significant improvement was noted from the outset of danazol therapy, and further improvement with long‐term therapy, as seen in the response of chronic ITP to danazol therapy. Danazol may offer lasting benefit in cyclic thrombocytopenia.
Atypical lymphocytes with a multilobated nucleus from a patient with tsutsugamushi disease (scrub typhus) in Japan
Authors: Iwasaki Hiromichi , Ueda Takanori , Uchida Michihiko , Nakamura Toru , Takada Nobuhiro , Mahara Fumihiko
Published: February 2007

A case of tsutsugamushi disease (scrub typhus) with atypical lymphocytes with a multilobated nucleus is reported. Although this type of atypical lymphocyte has been reported in patients with viral infections such as adult T‐cell leukemia, infectious mononucleosis, human immunodeficiency virus (HIV) infection, this is the first reported case of atypical lymphocyte with a multilobated nucleus in a patient with rickettsial infection. This type of atypical lymphocyte seems to exist in a broad spectrum of infectious diseases.
Eosinophilia resulting from administration of recombinant granulocyte‐macrophage colony‐stimulating factor (rhGM‐CSF) in a patient with T‐γ lymphoproliferative disease
Authors: Gonzales‐Chambers R. , Rosenfeld C. , Winkelstein A. , Dameshek L.
Published: February 2007

A therapeutic trial of recombinant human granulocyte‐macrophage colony‐stimulating factor (rhGM‐CSF) was attempted in a patient with neutropenia and frequent infections secondary to T‐γ lymphoproliferative disease (T‐γ LPD). During the 14 days of subcutaneous rhGM‐CSF (500 μg/m2/day), the absolute eosinophil count increased from 0 to 9,455/μl. By contrast, the absolute neutrophil count decreased. Toxicity related to rhGM‐CSF included arthralgia and nonspecific chest pain. The possible mechanism for the rhGM‐CSF induced selective eosinophilia is discussed.
Effect of reversible androgen deprivation on hemoglobin and serum immunoreactive erythropoietin in men
Authors: Weber Jed P. , Walsh Patrick C. , Peters Craig A. , Spivak Jerry L.
Published: February 2007

To examine the role of testosterone in the maintenance of hemoglobin levels, we studied the effect of reversible androgen deprivation on hemoglobin, serum immunoreactive erythropoietin, and serum testosterone in seven men treated with a luteinizing hormone‐releasing factor (LHRH) agonist for 6 months and then followed for an additional 6 months. The mean serum testosterone level was 4.35 ± 1.05 ng/ml initially and it decreased to castrate levels in all patients by 6 months. After stopping therapy, there was a rapid increase in serum testosterone such that by 12 months the mean concentration was normal. The pretreatment hemoglobin was 15.2 ± 0.9 g/dl (mean ± SD); after 6 months of androgen deprivation it had fallen to 14.1 ± 0.4 g/dl (P < 0.05). Six months after stopping therapy, the hemoglobin rose to pre‐treatment levels. Before treatment, serum immunoreactive erythropoietin was 9.5 ± 4.6 mu/ml (mean ± SD) and did not change significantly during or after the 6 month period of androgen deprivation. No significant inhibition of burst‐forming unit‐erythroid (BFU‐E) or colony‐forming unit‐granulocyte macrophage (CFU‐GM) was observed at the serum levels of nafarelin acetate obtainable in vivo. These data suggest that, within the normal range of hemoglobin in men, androgens are a determinant of the red cell mass.
Platelet lipoxygenase defect (wien‐penzing defect) in two patients with myocardial infarction
Authors: Sinzinger Helmut , Kaliman Josef , O'Grady John
Published: February 2007

In 2 male patients (35 and 38 years) presenting with myocardial infarction an abnormal conversion of exogenous 14C‐arachidonic acid by the patients' platelets, incubated in vitro, was observed. Neither patient's platelets showed evidence of a lipoxygenase pathway.

Platelet thromboxane formation from exogenous and endogenous substrate was high, while the platelet aggregation responses were normal. A myeloproliferative syndrome was excluded by bone marrow puncture. Similar defects have only been described so far in patients with myeloproliferative syndrome. This defect may be causative for the onset of clinical thrombotic events. It is speculative whether in vivo therapy with r‐IFNα1c might be able to eradicate the pathological platelet clone.
Role of leukocytes in the activation of intravascular coagulation in patients with septicemia
Authors: Okajima Kenji , Yang Wang‐Peng , Okabe Hiroaki , Inoue Masayasu , Takatsuki Kiyoshi
Published: February 2007

To elucidate the role of leukocytes in intravascular coagulation in patients with septicemia, plasma levels of thrombin‐antithrombin III complex (TAT), soluble fibrin monomer complex (SFMC) and fibrinogen (Fbg) were determined in 33 patients with septicemia. Twenty of 33 patients revealed marked leukopenia caused by suppression of hematopoie‐sis by the administration of chemotherapeutic agents for the treatment of hematological malignancies; the total leukocyte count of these patients was < 1,000/μl. Thirteen of 33 patients showed normal or increased leukocyte counts. Plasma levels of TAT and SFMC in septicemic patients without leukopenia were significantly higher than in patients with leukopenia. Although plasma TAT and SFMC levels correlated well with the number of leukocytes, a more significant positive correlation was found between the number of monocytes and the levels of TAT and SFMC. Plasma levels of Fbg were significantly lower in patients without leukopenia than in patients with leukopenia. No significant correlation was found between the number of leukocytes and the levels of Fbg. However, a significant negative correlation was found between the number of monocytes and the levels of Fbg. TAT levels did not correlate with the number of platelets. The fibrinolytic system was activated only in septicemic patients without leukopenia, which may be explained by secondary fibrinolysis following leukocyte‐activated coagulation. These findings suggest that leukocytes, in particular monocytes, may play a critical role in the pathogenesis of intravascular coagulation in septicemia.
Therapy of the Kasabach‐Merritt syndrome with cryoprecipitate plus intra‐arterial thrombin and aminocaproic acid
Authors: Stahl Robert L. , Henderson J. Michael , Hooks Michael A. , Martin Louis G. , Duncan Alexander
Published: February 2007

A patient with the Kasabach‐Merritt syndrome with disseminated intravascular coagulopathy and congestive heart failure due to a giant hepatic cavernous hemangioma achieved thrombosis of his tumor with a combination of cryoprecipitate plus intra‐arterial thrombin and epsilon aminocaproic acid. This was documented by an absence of Indium 111‐labelled platelet sequestration, marked decrease in thrombin:antithrombin complex generation, and normalization of platelet count and fibrinogen. Interventional angiography with aminocaproic acid and thrombin is advocated in patients whose tumors are amenable to such an approach so as to avoid a systemic antifibrinolytic state.
Case report: Interleukin‐6 positive follicular hyperplasia in the lymph node of a patient with rheumatoid arthritis
Authors: Numata Yukiko , Matsuura Yasushi , Onishi Saburo , Yamamoto Yasutake , Ohno Fumitoshi , Tagoh Hiromi , Yoshizaki Kazuyuki , Fujimoto Shigeyoshi , Yamamoto Hiroshi
Published: February 2007

We examined interleukin‐6 production in the hyperplastic lymph node of a 77‐year‐old male rheumatoid arthritis patient with lymphadenopathy. The interleukin‐6 production of the lymph node was observed by both immunohistological staining and in vitro culture. The results suggest that interleukin‐6 plays a significant pathogenic role in the etiology of the lymphadenopathy seen in many rheumatoid arthritis patients.
Novel effect of cyclicization of the Arg‐Gly‐Asp‐containing peptide on vitronectin binding to platelets
Authors: Mohri Hiroshi , Hashimoto Yoshimi , Ohba Masataka , Kumagai Hiromichi , Ohkubo Takao
Published: February 2007

Vitronectin is one of the glycoproteins that mediate cell adhesion and spreading of a variety of cells through the RGD(S) sequence. Vitronectin is demonstrated to bind to glycoprotein IIb‐IIIa and play a role in platelet aggregation. Synthetic peptides containing the RGD(S) sequence can inhibit vitronectin binding to platelets, but the affinity of these peptides is less than 1/100th that of native vitronectin. The present study thus examined the ability of modified RGD(S)‐containing peptide to inhibit vitronectin binding to thrombin‐stimulated platelets. The cyclicization of GRGDSPA peptide was done by the linkage of NH2‐terminal glycin and the COOH‐terminal alanin. The circular dichroism spectrum of cyclic GRGDSPA peptide only showed negative minimum at approximately 220 nm, but those of other linear peptides such as GRGDSPA and GRGESPA had no effect. This result indicated that only the cyclic GRGDSPA peptide retained some conformational structure to restrict its flexibility. Inhibition experiments revealed that the affinities of the ligands for the receptor decreased in the order of vitronectin = fibronectin = fibrinogen = von Willebrand factor (vWF) > cyclic GRGDSPA peptide > GRGDSPA peptide. GRGESPA peptide had no effect. These results demonstrate that the conformational structure of the RGD(S) sequence plays the important role for the affinity of vitronectin binding to activated platelets and the increased affinity of the modified peptide is a prerequisite for the potential antithrombotic use.
The effect of rhGM‐CSF on the proliferation of osteogenic sarcoma cells
Authors: Baker W. Jeffrey , Hargis Jeffrey B. , Danesi Romano , La Rocca Renato V.
Published: February 2007

Recombinant human granulocyte–macrophage colony‐stimulating factor (rhGM‐CSF) promotes the growth of a variety of hematopoietic and nonhematopoietic cells, both benign and malignant. There is now evidence that osteoblast‐like cells produce GM‐CSF and their growth is stimulated by this cytokine in vitro. We have studied the effect of rhGM‐CSF on DNA synthesis and cell proliferation in the human osteogenic sarcoma cell lines U‐20S, G‐292, MG‐63, and HOS. RhGM‐CSF stimulated a dose‐dependent increase in radioactive thymidine incorporation in each of the four cell lines in the presence of serum‐free media, and in two cell lines (HOS and U‐20S) in the presence of fetal bovine serum (FBS). In addition, rhGM‐CSF produced significant increases in cell proliferation in two cell lines (MG‐63 and U‐20S) in the presence of 2% FBS. These results suggest that GM‐CSF may have an important role in the biology of human osteogenic sarcoma cells. The clinical implications of these findings merit further investigation.
Evaluation of continuous infusion low‐dose 5‐azacytidine in the treatment of myelodysplastic syndromes
Authors: Chitambar Christopher R. , Libnoch Joseph A. , Matthaeus William G. , Ash Robert C. , Ritch Paul S. , Anderson Tom
Published: February 2007

The treatment of myelodysplastic syndromes (MDS) is both difficult and controversial. In the current study, we evaluated the efficacy of low‐dose 5‐azacytidine in the treatment of this disorder. Fifteen patients with MDS were entered on study to be treated with 5‐azacytidine by continuous intravenous infusion for 14 days. Doses of the drug ranged from 10 mg/m2/day to 35 mg/m2/day, with most patients receiving 16.5 mg/m2/day. In two patients, the drug was stopped early in the course of treatment because of thrombocytopenia. Thirteen patients completed therapy according to protocol. Three of 13 patients demonstrated a partial response to therapy. Of these three patients, one had an increase in platelet and absolute neutrophil counts, while the other two no longer required support with red cell transfusions. The drug was well tolerated and significant myelosuppression did not occur in most patients. Low‐dose 5‐azacytidine appears to have activity in the treatment of primary MDS and future studies should consider evaluation of this drug in combination with hematopoietic growth factors.
Anaplastic large cell Ki‐1 lymphoma involving bone marrow: Marrow findings and association with reactive hemophagocytosis
Authors: Wong K. F. , Chan J. K. C. , Ng C. S. , Chu Y. C. , Lam P. W. Y. , Yuen H. L.
Published: February 2007

This report describes the bone marrow findings in four patients whose marrow was involved by anaplastic large‐cell Ki‐1 lymphoma, an uncommon event in this type of lymphoma. In the marrow aspirate smears, the involvement was subtle, and was in the form of isolated large cells with irregular nuclear configuration, coarse chromatin, prominent nucleoli, and basophilic cytoplasm which might be vacuolated. One case showed paradoxically massive involvement in the trephine biopsy taken from the same site as the marrow aspirate. Reactive histiocytic proliferation with hemophagocytosis was also present. Since marrow aspirate or biopsy may be the first pathologic specimen examined in patients having anaplastic large‐cell Ki‐1 Iymphoma, it is important to be able to recognize the small population of neoplastic cells, which should lead to prompt treatment or further investigations as deemed necessary.
Splenic function in persons with sickle cell trait at moderately high altitude
Authors: Nuss Rachelle , Feyerabend Angela J. , Lear James L. , Lane Peter A.
Published: February 2007

We investigated the possibility that persons with sickle cell trait who reside chronically at moderately high altitude might develop impaired splenic reticuloendothelial function. Seventeen healthy young black men with sickle trait who had lived at ⩾ 1,609 m for ⩾ 10 years participated in the study along with 25 matched control subjects with normal hemoglobin. Splenic function was assessed by radionuclide liver‐spleen scanning and by red cell pit counts. No evidence of impaired splenic function was found in the sickle trait group. The data suggest that long‐term residence at moderately high altitude does not place persons with sickle cell trait at risk for splenic dysfunction.
Plasma adenosine deaminase2, is a marker for human immunodeficiency virus‐1 seroconversion
Authors: Niedzwicki John G. , Mayer Kenneth H. , Abushanab Elie , Abernethy Darrell R.
Published: February 2007

Plasma adenosine deaminase2, (ADA2) has recently been proposed to be a marker for human immunodeficiency virus‐1 (HIV) infection. We measured ADA2, levels in plasma from two groups of white homosexual males at 6‐month intervals for a total of 2.5 years. One group consisted of 6 subjects who seroconverted for HIV, and the other consisted of 8 HIV seropositive patients who progressed from asymptomatic (CDC Groups II/III) to symptomatic (CDC Group IV) disease. Seroconversion was associated with a significant increase in plasma ADA2 which persisted throughout follow‐up of 1.5 years. However, disease progression in HIV seropositive patients was not associated with any significant change in plasma ADA2 In conclusion, ADA2, may represent a unique marker for HIV seroconversion which does not change with later progression to symptomatic disease.
Protein C and S levels in acute leukemia
Authors: Troy Kevin , Essex David , Rand Jacob , Lema Myra , Cuttner Janet
Published: February 2007

Patients with acute leukemia undergoing remission induction chemotherapy occasionally develop venous thrombosis despite severe thrombocytopenia and in the absence of disseminated intravascular coagulation. This observation prompted us to study the levels of the naturally occurring anticoagulant proteins C and S prospectively in patient sundergoing remission induction chemotherapy for acute leukemia. Plasma samples from 50 adult patients with acute leukemia (34 AML, 16 ALL) were analyzed for protein C antigen, functional protein C, immunologic total and free protein S as well as levels of C4b binding protein (C4bBP). Plasma levels of immunolgic protein C were significantly lower in patients with active acute myelocytic leukemia (mean = 77.9) than in controls (mean = 123.6) or patients in remission (mean = 132). Functional protein C levels were also significantly lower in AML patients with active disease (mean = 58.5) than controls (mean = 95.5) or patients in remission (mean = 98.5). Patients with acute lymphocytic leukemia (ALL) had normal levels of immunologic and functional protein C. Although total protein S levels were normal in all patients studied, levels of free protein Swere significantly decreased in patients with active AML (mean = 29.3) compared with patients in remission (mean = 42.0) or controls (mean = 42.4). In contrast, patients with ALL, both with active disease and in remission had normal free protein S levels. This decrease in free protein S seen in active AML was not associated with liver disease, white cell count or an increase in C4bBP. These findings provide a possible explanation for the occasional occurrence of venous thrombosis in patients with acute myelocytic leukemia.
CD5 positive immunoregulatory B cells in spleen populations from multiple myeloma patients
Authors: MacKenzie Malcolm R. , Paglieroni Teresa , Caggiano Vincent
Published: February 2007

CD19+CD5+ lymphocytes constitute a minority of peripheral blood B cells. In view of the importance of these cells in the pathogenesis of the immunoregulation of myeloma, their incidence in another lymphoid organ was determined. CD5+ B cells were studied in 9 spleens from patients with multiple myeloma and in 10 spleens from normal individuals removed secondary to trauma. The total number of CD19+ B cells were increased in myeloma spleens (44.4% ± 12.6%) as compared to normal spleens (20.4% ± 7.4%). Likewise, the percentage of CD19 cells which co‐expressed CD5 were increased in myeloma (25.3% ± 12.4%) versus normal (4.4% ± 2.3%) spleen. CD5+ B cells isolated from myeloma spleens, but not normal spleens, inhibit production of immunoglobulin in a pokeweed mitogen driven assay. Thus the spleen appears to be an important source of immunoregulatory B cells in multiple myeloma.
Computed tomography for diagnosis of hepatic rupture in primary systemic amyloidosis
Authors: Gastineau Dennis A. , Gertz Morie A. , Rosen Charles B. , Kyle Robert A.
Published: February 2007

Hepatic rupture in primary systemic amyloidosis is extremely ominous; death occurs in hours to days. We present two cases of hepatic rupture diagnosed ante mortem with computed tomography (CT). Surgical repair was possible in one instance and successfully controlled the bleeding. In the setting of primary amyloidosis, the early use of CT scanning for undiagnosed ascites, hypotension, or rapid organ enlargement may lead to early diagnosis and potential surgical correction.
Retroperitoneal fibrosis accompanying immune thrombocytopenia
Authors: Wallach Paul M. , Flannery Michael T. , Adelman Harold M. , Powsang Julio , Saba Hussein , Altus Philip , Espinoza Luis R.
Published: February 2007

Retroperitoneal fibrosis represents an idiopathic systemic fibrosing syndrome which leads to the development of progressive hydronephrosis and azotemia (Stewart and Friberg: Southern Medical Journal 77:1185–1187, 1984; Morad et al.: American Journal of Medicine 82:363–366, 1987). Evidence in the literature supports a hypothesis that retroperitoneal fibrosis represents a systemic autoimmune process (Lichon et al.: Journal of Rheumatology 11:373,374, 1984; Lipman et al.: JAMA 196:204–206, 1966; Littlejohn and Keystone: Journal Rheumatology 8:665–669, 1981; Katz et al.: American Journal of Clinical Pathology 67:436–439, 1977). We report a case of a patient with retroperitoneal fibrosis, immune thrombocytopenia, presence of antinuclear antibody, and direct Coombs positivity which provides further evidence that retroperitoneal fibrosis is an autoimmune process. Progressive obstructive uropathy related to his fibrosis led to bilateral hydronephrosis and significant renal function impairment. Also, he developed marked immune thrombocytopenia. Treatment with prednisone produced a dramatic response in both platelet count and renal function.
Agranlocytosis caused by ticlopindine and its mechanism
Authors: Ono Kazutoshi , Kurohara Kazuhiro , Yoshihara Masahiro , Shimamoto Yoshinori , Yamaguchi Masaya
Published: February 2007

A 75‐year‐old female patient with agranulocytosis caused by ticlopidine is reported. She took the drug at 200 mg/day for 30 days to prevent recurrence of cerebral infarction. The leukocyte count at the nadir was 500/μl on the 34th day since she started to take the drug. Complete recovery of her peripheral leukocytes came 12 days after its withdrawal. In this patient, mechanisms of ticlopidine‐caused agranulocytosis were studied. The lymphocyte stimulation test using ticlopidine was negative. In the culture of marrow cells depleted of lymphocytes, ticlopidine directly inhibited the CFU‐C in a dose‐dependent manner. Neither the serum on the day of admission nor the T‐lymphocytes pre‐cultured with ticlopidine had any effect on the CFU‐C. The lymphocyte stimulation test is useless in an attempt to find the causal drug in agranulocytosis if it is caused in a directly toxic manner. Agranulocytosis caused by ticlopidine is rare, but careful follow‐up is necessary in the case of patients on the drug because there are some whose marrow cells are very sensitive to it.
Flow cytometric analysis of anti‐platelet antibodies in patients with chronic idiopathic thrombocytopenic purpura (ITP) using acid‐treated, formalin‐fixed platelets
Authors: Mizumoto Y. , Fujimura Y. , Nishikawa K. , Uchida M. , Fukui H. , Morii T. , Narita N. , Kurata Y.
Published: February 2007

Acid treatment of normal washed platelets prepared by albumin density gradient centrifugation followed by formalin fixation effectively eliminates HLA class I antigens from the platelet surface, without altering the immunoreactivity of platelet membrane glycoproteins Ib and IIb/IIIa complex. Using these platelets, flow cytometric analysis was performed on a total of 20 sera from different patients with chronic ITP, and revealed an inverse linear correlation between the platelet count and the mean fluorescence intensity which represents a relative amount of platelet‐bound IgG. These results suggest that acid‐treated, formalin‐fixed platelets can be used as specimens to detect anti‐platelet antibodies to differentiate from those to HLA‐class I antigens.
Hemopoietic inhibition in hairy cell leukemia
Authors: Janckila Anthony J. , Gentile Patrick S. , Yam Lung T.
Published: February 2007

Leukopenia, thrombocytopenia, and anemia are important features of hairy cell leukemia (HCL). They are generally considered to be due to hypersplenism and to inadequate production by bone marrow which is heavily infiltrated by the neoplastic hairy cells (HC). However, the cytopenias may also be caused by hemopoietic inhibition by cytokines derived from the mononuclear cells (MNC) of HCL. We studied the MNC of HCL with an in vitro assay for granulocyte‐macrophage progenitors (CFU‐GM) to search for this hemopoietic inhibitor(s) and to determine the cell source and mechanism of its production/release. We found that MNC conditioned media from 7 of 9 HCL cases exerted substantial inhibitory effect (23% to 66%) on normal marrow cells. Peak inhibitory activity was obtained in media conditioned with 106 MNC/ml for 90 minutes to 24 hours. Both HC and lymphocytes could release inhibitor(s) through mutually synergistic cell interactions. HC alone were inactive and lymphocytes alone were only weakly active. Mixtures of conditioned media of HC and of lymphocytes were not synergistic. The lymphocytes responsible for the inhibition were present in preparations depleted of cells bearing the cluster designation 4 antigen (CD4+) and B cells and were most likely the CD8− T‐cells. In one patient so examined, a partial reversal of inhibition was achieved by treating MNC‐CM with antibodies to tumor necrosis factor (TNF)‐alpha suggesting that TNF‐alpha was at least partly involved in the inhibition of CFU‐GM. This mechanism of cytokine release may be operative in vivo to account for the cytopenias in HCL and, if so, could alter the concept of hypersplenism in this disease.
The effect of 1‐hydroxyvitamin D3 for prolongation of leukemic transformation‐free survival in myelodysplastic syndromes
Authors: Motomura Shigeki , Kanamori Heiwa , Ohkubo Takao , Maruta Atsuo , Kodama Fumio
Published: February 2007

Leukemic transformation (LT) free survival was studied in 30 patients with myelodysplastic syndromes (MDS). In 15 cases, 4–6 μg/day of 1‐hydroxyvitamin D3 was administered, for a median duration of 17 months (D‐group), other subjects had no therapy (N group). LT free survival of the D group had significant advantage over that of the N group according to the Kaplan—Meier method (P < 0.001). In addition, 7 cases in the N group developed acute leukemia, in contrast to only one in the D group (P < 0.05). These results suggest that oral administration of 1‐hydroxyvitamin D3 prevents the progression of MDS to overt leukemia under the effect of differentiation capacity from blasts to monocytes.
Unexpectedly high toxicity of MACOP‐B in young patients with low grade lymphoma
Authors: Arranz R. , Peréz G. , Steegmann J. L. , Cámara R. , Tomás J. F. , Figuera A. , Vazquez L. , Fernández‐Rañada J. M.
Published: February 2007

We report the results of treatment with MACOP‐B in 11 young patients with low grade lymphoma (LGL). Complete remission was obtained in 4 (57%) and partial remission in 3 (42.8%) of 7 evaluable patients. However, this aggressive chemotherapy has not offered any advantage because of an unacceptably high treatment‐related morbidity and mortality (17%). Serious infection during neutropenia was the most common complication.
Significance of hemostatic molecular markers during disseminated intravascular coagulation in patients with liver cirrhosis treated by endoscopic embolization for esophageal varices
Authors: Koyama Tetsuji , Kakishita Eizo , Nakai Yoshiyuki , Okamoto Eizo
Published: February 2007

We studied the quantitative changes of hemostatic molecular markers with time during the course of disseminated intravascular coagulation (DIC) induced by endoscopic embolization using thrombin for esophageal varices in nine patients with liver cirrhosis. The plasma levels of D–dimer, a product of plasmin degradation of cross‐linked fibrin, and thrombin–antithrombin‐III complex (TAT) were significantly higher in patients before treatment when compared with 60 healthy individuals. The plasma levels of TAT, D‐dimer, and plasmin α2‐plasmin inhibitor complex (PIC) increased significantly 5–15 min after thrombin injection into the varices, earlier than the changes of conventional coagulofibrinolytic factors, reached a maximum level after 180 min, and started to decline after 1 day. Although the plasma PIC level returned to normal after 7 days, both TAT and D‐dimer were still above the pretreatment level.

Although there was no change in urokinase‐type plasminogen activator (u‐PA), tissue‐type plasminogen activator (t‐PA) increased significantly after 5 min. The plasma level of plasminogen activator inhibitor type 1 (PAI‐1) showed only a slight elevation after treatment. We propose that the hemostatic molecular markers TAT, D‐dimer, and PIC are suitable for the early diagnosis of DIC after endoscopic embolization using thrombin in patients with liver cirrhosis and that the increase of PAI‐1 is too small for the regulation of fibrinolysis due to t‐PA in DIC occurring in liver cirrhosis.
Circulating thrombomodulin in thrombotic thrombocytopenic purpura
Authors: Takahashi Hoyu , Hanano Masaharu , Wada Ken , Tatewaki Wataru , Niwano Hiroe , Shibata Akira , Tsubouchi Jiro , Nakano Masahiko , Nakamura Tadao
Published: February 2007

Endothelial cell injury is thought to be one of the causative factors in thrombotic thrombocytopenic purpura (TTP). A novel index of endothelial injury, plasma thrombomodulin, was measured in 13 patients with acute TTP. The mean plasma concentration of thrombomodulin was elevated in patients with TTP (34.23 ± 19.08 ng/ml) as compared with healthy subjects (16.99 ± 2.63 ng/ml, P <0.001). Eight (61.5%) of 13 patients had high thrombomodulin values. Markedly elevated thrombomodulin levels were observed in TTP patients who had suffered from systemic lupus erythematosus, in whom plasma thrombomodulin was still elevated when they achieved remission. Five of these 13 patients with TTP had normal plasma levels of thrombomodulin. In addition, the plasma thrombomodulin concentrations were correlated well with von Willebrand factor antigen and tissuetype plasminogen activator antigen levels, both of which are released from stimulated or damaged endothelial cells. No difference was found in plasma thrombomodulin levels between patients who achieved remission and who did not. These findings suggest that the magnitude of the endothelial damage in TTP is variable among patients and that plasma thrombomodulin has limited clinical relevance to the severity of TTP.
In vivo efficacy of intravenous gammaglobulins in patients with lupus anticoagulant is not mediated by an anti‐idiotypic mechanism
Authors: Galli Monica , Cortelazzo Sergio , Barbui Tiziano
Published: February 2007

The authors have investigated the presence in commercially available intravenous gammaglobulins (IVlg) of anti‐idiotypic antibodies directed to Lupus Anticoagulant (LA). In vitro incubation of 4 LA plasmas with increasing concentrations of IVlg (from 0 to 39 mg/ml) resulted in a dose‐dependent inhibition of LA activity (the highest inhibitions ranged from 14.0 to 53.4%). Similar results were obtained when patients' plasma was substituted with total IgG (the highest inhibitions ranged from 43.0 to 55.0% and were obtained at IgG:IVIg molar ratios ranging from 1:15 to 1:50). Also the incubation of patients' F(ab's)2 with F(ab')2 from IVIg produced a similar dose‐dependent inhibition of LA activity. These data are suggestive of an in vitro idiotypic‐anti‐idiotypic interaction between LA and IVIg. However, when injected in patients with LA, IVIG do not seem to operate by this mechanism of action. In fact, reduction or disappearance of LA was only observed in 2 out of 4 patients; also the quick reappearance of LA activity was not consistent with the time course of anti‐idiotypic response. Finally, this effect was reached by half the IVIg concentrations necessary to produce an appreciable inhibitory effect on LA activity in vitro. Thus, it is concluded that, even if IVIg contain anti‐idiotypic antibodies reacting with LA, the clinical efficacy of IVIg treatment in patients with these autoantibodies should be attributed to other mechanisms.
Detection of immunoglobulin gene rearrangement in acute and chronic lymphoid leukemias of B‐cell lineage by polymerase chain reaction gene amplification
Authors: Liang Raymond , Chan Vivian , Chan T. K. , Wong Thomas , Chiu Edmond , Todd David
Published: February 2007

Polymerase chain reaction (PCR) was used to amplify the DNA fragments of the complementarity determining region 3 of the immunoglobulin (Ig) gene heavy chain from the leukemic cell specimens of patients with acute and chronic lymphoid leukemias of B‐cell lineage. Two different pairs of primers were tested. Fourteen of the 17 (82%) cases of acute lymphoblastic leukemia (ALL), and all 15 cases (100%) of B‐cell chronic lymphocytic leukemia, who had rearrangement of the Ig gene heavy chain by Southern analysis, were positive by PCR with either one or both pairs of primers. This technique was able to detect leukemic cells at the level of 0.1%. Applying it to study the remission marrow specimens following induction chemotherapy was more useful than morphology alone in predicting early relapse of the leukemia.
Analysis of N‐ras gene mutations in acute myeloid leukemia by allele specific restriction analysis
Authors: Todd A. V. , Ireland C. M. , Radloff T. J. , Kronenberg H. , Iland H. J.
Published: February 2007

N‐ras gene activation occurs via single base substitutions in codons 12, 13, and 61. We have developed a rapid screening method, termed allele specific restriction analysis (ASRA), for detection of N‐ras mutations at these three critical codons in acute myeloid leukemia (AML). Patient DNA samples are amplified by the polymerase chain reaction (PCR) by using primers that induce restriction sites in normal but not mutant N‐ras alleles. We have used ASRA to identify 5 point mutations in four out of 19 patients at initial presentation of de novo AML. Three patients had one mutation at codon 12, 13, or 61 respectively, while a fourth patient had concurrent mutations at codons 12 and 13. N‐ras mutations were more common in patients over 65 years of age (P < 0.04), but did not correlate with FAB classification, attainment of complete remission, disease free survival, or overall survival. ASRA can also be used as the first step in a more sensitive approach to the detection of ras mutations. When ASRA was combined with allele specific oligonucleotide (ASO) hybridization the sensitivity and specificity of these assays were increased. This allowed identification of additional low level mutations in two patients. The data presented here constitute the first complete analysis of N‐ras mutations in leukemia by ASRA and include the first identification of three concurrent N‐ras mutations in a single leukemic patient. By facilitating sensitive sequential studies, ASRA should contribute to our understanding of the role of N‐ras mutations in leukemogenesis.
Granulocytic sarcoma of the ovary in patients with acute myelogenous leukemia
Authors: Yamamoto Kou , Akiyama Hideki , Maruyama Tamotsu , Sakamaki Hisashi , Onozawa Yasusuke , Kawaguchi Kenji
Published: February 2007

Two cases of granulocytic sarcoma of the ovary found at the time of relapse of acute myelogenous leukemia (AML) are presented. Almost 5 years after the initial diagnosis of AML, both cases presented ovarian tumors which were discovered to be myeloblastoma of the ovary on laparotomy in one case and at the time of autopsy in the other. Evidence of hematological relapse followed the presentation of the ovarian tumor within a month. Both patients were treated with surgery and/or chemotherapy.
Increased levels of tissue plasminogen activator with a low plasminogen activator inhibitor‐1 in a patient with postoperative bleeding
Authors: Stankiewicz Andrzej J. , Crowley James P. , Steiner Manfred
Published: February 2007

Recurrent postoperative bleeding in a previously healthy man with a moderate prolongation of PT and PTT which did not correct with vigorous fresh‐frozen plasma infusion was identified as a unique abnormality of the fibrinolytic system: a combination of an excess of tissue plasminogen activator (t‐PA) at 300% of normal activity accompanied by a concurrent deficiency of plasminogen activator inhibitor‐1 activity (PAI‐1) of 10‐20% of normal activity. This observation underscores the potentially important regulatory role of PAI‐1 in the degree to which clinical manifestations of bleeding tendencies may occur in patients in whom an excess amount of t‐PA is expressed.
Successful management of Ph chromosome chronic myelogenous leukemia with leukapheresis during pregnancy
Authors: Bazarbashi M. Shouki , Smith Mitchell R. , Karanes Chatchada , Zielinski Irene , Bishop Carter R.
Published: February 2007

We report the successful management of a 25 year‐old woman diagnosed in the second trimester of her pregnancy with chronic myelogenous leukemia (CML). She was treated with leukapheresis until her delivery at 38 weeks of gestation. The procedure was without significant adverse effects on the patient or the fetus. Following induced vaginal delivery, the patient underwent allogeneic bone marrow transplantation from her HLA‐matched brother and is presently disease free 13 months following her transplant.
Immunologic thrombocytopenia followed by thrombotic thrombocytopenic purpura in two HIV1 patients
Authors: Routy Jean‐Pierre , Beaulieu Raymond , Monte Marc , Saint‐Louis Jean , Sauvageau Guy , Toma Emil
Published: February 2007

Two homosexual HIV1‐positive male patients with thrombotic thrombopenic purpura (TTP) were found to have past history of immune thrombocytopenia (ITP). The first patient had ITP 10 months prior to TTP and was successfully treated by splenectomy. The second patient had ITP 32 months before TTP. No specific treatment was given for his asymptomatic ITP. Association of HIV infection to TTP seems to be frequent. These two types of purpura have different pathogenic mechanisms but share a common altered immune response to antigenic challenge. The occurrence of ITP and TTP in HIV‐positive patients may lead to errors in diagnosis and therapy.
Heterozygous β‐thalassemia: Relationship between the hematological phenotype and the type of β‐thalassemia mutation
Authors: Rosatelli C. , Leoni G. B. , Tuveri T. , Scalas M. T. , Mosca A. , Galanello R. , Gasperini D. , Cao A.
Published: February 2007

In this study we have correlated the severity of the hematological features to the type of the β‐thalassemia mutation [codon 39 (C→T), IVS‐I nt 110 (G→A), IVS‐I nt 1 (G→A), IVS‐I nt 6 (T→C), IVS‐II nt 745 (C→G), −87 (C→G) and β6 (‐1bp)], in a group of β‐thalassemia heterozygotes of Italian descent in whom we excluded the presence of iron deficiency or deletion α‐thalassemia. The β‐thalassemia mutation was defined by dot blot analysis on amplified DNA with allelic specific oligonucleotide probes. We found that (a) heterozygotes for β+ IVS‐I nt 6 and β+ ‐ 87 mutations produce larger and better hemoglobinized red blood cells, and )b) heterozygotes for β+IVS‐I nt 6 and β+IVS‐I nt 110 mutations have a less marked increase of Hb A2 levels as compared to heterozygotes for the other mutations investigated. These findings indicate that milder β‐thalassemia mutations such as the β+IVS‐I nt 6 and β+ ‐ 87, express also in the heterozygous state a milder phenotype as compared to β°+‐thalassemia or severe β+ thalassemia (β+IVS‐I, nt 110. The Hb A2 levels, on the other hand, were not related to the severity of the mutation because of less marked increase was found in a mild (β+IVS‐I nt 6) as well in a severe (β+IVS‐I nt 110) mutation. From the practical point of view these findings should be adequately considered in carrier screening and genetic counselling.