bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased circulating endothelial cells in sickle cell crisis
Authors: Sowemimo‐Coker Samuel O. , Meiselman Herbert J. , Francis Robert B.
Published: February 2007

To determine whether increased numbers of circulating endothelial cells, a possible indicator of endothelial injury, are present in subjects with sickle cell disease, we measured circulating endothelial cells in 30 normal subjects and in 23 subjects with sickle cell anemia. Mean circulating endothelial cells were significantly higher (P < 0.025) in the sickle cell subjects than in the normal subjects. Circulating endothelial cells were significantly higher than normal in 10 sickle cell subjects studied during painful crisis (P < 0.01) but not in 13 sickle cell subjects studied while in the steady state. To control for the known stimulatory effect of cigarette smoking on circulating endothelial cells, we analyzed the results for smokers and nonsmokers separately. Mean circulating endothelial cells were not significantly higher in sickle cell subjects who smoked (n = 10) than in normal subjects who smoked (n = 8), but were significantly higher (P < 0.05) in sickle cell nonsmokers (n = 13) than in normal nonsmokers (n = 22). Among nonsmoking sickle cell subjects, mean circulating endothelial cells were significantly higher than normal (P < 0.01) during painful crisis (n = 7), but not in the steady state (n = 6). We conclude that circulating endothelial cells are significantly increased in sickle cell crisis, and may indicate the occurrence of acute endothelial injury during episodes of microvascular occlusion.
Ultrastructure of multinucleated giant myeloma cells: Report of one case
Authors: Kurabayashi Hitoshi , Miyawaki Shuichi , Murakami Hirokazu , Nemoto Kazuo , Sawamura Morio , Kubota Kazuo , Naruse Takuji , Tsuchiya Jun
Published: February 2007

The ultrastructure of multinucleated giant myeloma cells obtained from an IgAk myeloma patient was investigated. The characteristic findings were marked nucleocytoplasmic asynchrony, irregular nuclear indentation, branched mitochondria, and Golgi apparatus surrounded by nuclei. The patient died of renal failure only 6 months after diagnosis.
Renal transplantation from a blood group A1B donor to an A2B recipient: A case report
Authors: Albornoz Gonzalo , Korb Steven , Kolovich Richard , Light Jimmy A.
Published: February 2007

This case report describes the transplantation of a kidney from an A1B donor to a recipient who was blood group A2B. The donor/recipient pair were ABO mismatched but compatible. In the majority of cases, A1 antibodies fail to react at 37°C and are of no clinical significance. However, hemolytic transfusion reactions due to A1 antibodies active at 37°C have been reported but are extremely rare. When the opportunity for transplantation arose for this patient, who had received multiple blood transfusions because of dialysis, the question of safety concerning the subject of transplanting across ABO sub‐grouping mismatches was presented. Inquiries regarding this matter proved fruitless and the transplant was performed mainly due to the lack of preformed anti‐A1 antibodies in the recipient at the time of transplant. It was hoped that the A2B recipient would fail to make an anti‐A1 antibody due to antigen exposure or if it did, would not pose a hazard to the allograft. Therefore we present our experience with a patient who was successfully transplanted across an ABO incompatible sub‐grouping, A1B allograft to an A2B recipient.
History and implications of the neutrophil glycoprotein deficiencies
Authors: Styrt Barbara
Published: February 2007

This review focuses on the initial clinical descriptions and subsequent investigation of the syndrome of recurrent infections associated with neutrophil membrane glycoprotein deficiencies. Characterization of the missing group of three glycoprotein heterodimers and their role in adhesion‐related neutrophil function is summarized. Study of the clinical consequences of these genetically determined membrane glycoprotein defects has also contributed to the understanding of the role of normal neutrophils in both host defense and host tissue damage.
Fibrinogenolysis in thrombotic thrombocytopenic purpura
Authors: Kakishita Eizo , Koyama Tetsuji , Higuchi Mitsuhiro , Kunitomi Osamu , Oura Yoshio , Nagai Kiyoyasu
Published: February 2007

Coagulo‐fibrinolytic factors were studied in five patients suffering from thrombotic thrombocytopenic purpura (TTP). The change in coagulation factors in the acute stage was mild compared with that found in disseminated intravascular coagulation (DIC). We observed a slight increase of fibrin‐fibrinogen degradation products (FDP) in the plasma of four patients during the acute stage of TTP, but the level of the D‐dimer remained within normal variation and was extremely low compared with that in 27 samples from patients with DIC showing the same level of FDP. At the same time, both antigen levels of tissue‐type plasminogen activator (t‐PA) and plasminogen activator inhibitor type 1 (PAI‐1) were elevated in three of the four patients tested. Although a similar change was recognized in DIC patients' plasma, the elevation of PAI‐1 in the acute stage of TTP was far higher than in overt DIC. The antigen levels of t‐PA and PAI‐1 were normal in remission, and a mild elevation of PAI‐1 was detected in one of the three patients during the early stage of TTP relapse. Enzymography revealed the appearance of free t‐PA and an increase of a substance with a 110 kD molecule, assumed to be a t‐PA and PAI‐1 complex, in TTP plasma in the acute stage, but the findings were normal for plasma from cases in remission and the early stage of relapse. Enzymography also showed a decrease of urokinase‐type plasminogen activator (u‐PA) only in the acute stage of TTP. These changes in the coagulo‐fibrinolytic factors in the acute stage of TTP suggest that fibrinogenolysis might be induced by t‐PA, released through vascular reaction at an uninvolved area of vascular lesions caused by platelet agglutinates, which would then release large amounts of PAI‐1 inhibiting t‐PA and u‐PA activities at the occlusive lesion.
Splenic cyst carcinoma presenting in pregnancy
Authors: Elit L. , Aylward B.
Published: February 2007

A case report of squamous cell carcinoma in an epidermoid cyst of the spleen is diagnosed in a pregnant female. Elaboration on the clinical, radiological, and pathological findings is presented to emphasize the distinguishing features of benign and malignant cysts.
Platelet survival in patients with beta‐thalassemia
Authors: Eldor A. , Krausz Y. , Atlan H. , Snyder D. , Goldfarb A. , Hy‐Am E. , Rachmilewitz E. A. , Kotze H. F. , Heyns A. Du P.
Published: February 2007

Thromboembolic events associated with significant morbidity and mortality have been observed in patients with beta‐thalassemia major (TM). These include arterial as well as venous thrombosis and the development of early arteriosclerosis. To elucidate the possibility that TM patients may develop a hypercoagulable state we carried out a study of platelet kinetics on ten patients with TM and four patients with thalassemia intermedia (TI). Autologous platelets were labeled with indium‐111‐oxine, and the platelet lifespan (PLS) was determined. A significant shortening of PLS was observed in 13 out of 14 patients examined. The mean PLS (±1 SD) in ten patients (8 TM, 2 TI) who underwent splenectomy was 107 ± 36 hr (control splenectomized 248 + 51 hr) (P < .001) and in four nonsplenectomized patients (2 TM, 2 TI) was 102 ± 64 hr (control 224 + 23 hr) (P < .01). The short PLS in addition to reported findings of increased circulating platelet aggregates and the decreased response of TM platelets to aggregating agents suggests in vivo platelet activation in thalassemic patients.
Effect of hydroxyurea on the rheological properties of sickle erythrocytes in vivo
Authors: Ballas Samir K. , Dover George J. , Charache Samuel
Published: February 2007

We have monitored the rheological effects of hydroxyurea (HU) on erythrocytes obtained from two patients with severe sickle cell anemia who were enrolled in a therapeutic trial of this drug. Erythrocyte membrane stability and whole cell and membrane deformability of red cells from treated and untreated patients and normal controls were determined in room air using an ektacytometer—a laser viscodiffractometer. The percentage of dense cells was quantitated by centrifugation on a discontinuous Stractan density gradient. F reticulocytes (FR), absolute F reticulocytes (AFR), and F cells (FC) were determined by single‐cell radial immunolgic assays. After 1 year of treatment with HU, there was a significant increase in the level of hemoglobin (Hb) F, FR, AFR, and FC. The degree of anemia remained the same, but there was significant increase in the mean cell volume (MCV) and a significant decrease in the mean corpuscular Hb concentration (MCHC). Whole cell deformability improved by twofold, but membrane stability remained within normal limits. The hydration status of sickle erythrocytes improved as was indicated by a change toward normal in gradient osmotic ektacytometry, an increase in RBC K+ content, a decrease in percent of dense cells, and a decrease in the MCHC. The data indicate that, in addition to its effect on the production of Hb F, HU has a salutary effect on whole cell deformability and on the hydration status of sickle erythrocytes. Determination of the rheological properties of erythrocytes may be of value in monitoring the response to HU.
Hemoglobin Athens‐Georgia [α2 β2 40(C6)Arg→Lys] in association with β0‐thalassemia in Tunisia
Authors: Mrad A. , Kister J. , Feo C. , Poyart C. , Kastally R. , Blibech R. , Galacteros F. , Wajcman H.
Published: February 2007

We describe an Hb Athens‐Georgia (Hb A‐Ga)/β0‐thalassemia compound heterozygosity, found in a Tunisian patient. Oxygen binding studies of red cell suspensions of this patient, containing approximately 95% Hb A‐Ga, revealed an almost normal oxygen affinity. Nevertheless, dilute solutions of Hb A‐Ga showed an increased overall oxygen affinity and decreased heme‐heme interaction. This could be explained by a tetrameric hemoglobin with normal oxygen binding properties but with increased dissociation into monomers or dimers, as a consequence of a structural abnormality within the α1β2 interface. Such an interpretation would explain the increased oxygen affinity reported in previous studies performed on heterozygous Hb A/Hb A‐Ga patients.
Leukostasis: A phenomenon of prolymphocytic leukemia
Authors: Megaludis Alexis M. , Winkelstein Alan , Zeigler Zella R. , Miller Thomas R.
Published: February 2007

We are reporting a case of a patient with prolymphoctic leukemia complicated by fatal leukostasis. Multiple leukemic thrombi and leukoaggregales were demonstrated on postmortem examination in both the brain and lungs. This represents the first report pathologically documenting leukostasis in a chronic lymphoid malignancy.
Time‐dependent cleavage of a high‐mannose form of Ii to p25 in an intracellular compartment
Authors: Thomas Lawrence J. , Humphreys Robert E. , Knapp Walter , Nguyen Quoc V.
Published: February 2007

The cleavage of a high‐mannose form of Ii to p25 was demonstrated in an intracellular compartment of B cells. Subcellular fractions of 72 hr‐activated B cells, separated by Percoll density gradient centrifugation, were immunoprecipitated with anti‐class II or anti‐I serum and characterized for 5′‐nucleotidase, acid phosphatase, and radiolabeled transferrin. The cleavage of p25 from li as a C‐terminal fragment occurred from 20 to 60 min after synthesis in an intracellular compartment which was intermediate in density between lysosomal and plasma membrane fractions and coincided with the lighter of two internalized transferrin compartments. Chloroquine or monensin treatments, at maximal nontoxic doses, which block Golgi and lysosomal functions, did not seem to alter the cleavage of 1i to p25. p25 molecules were reduced to about 10,500 daltons by treatment with endoglycosidases F or H. We conclude that p25 was generated from a high mannose form of Ii in the endoplasmic reticulum or cis‐Golgi. This finding could either implicate that site for class II MHC desetope charging with foreign peptides or reflect a mechanism for degradation of “excess” Ii molecules.
Geographic variability of hemophilia‐associated aids in the United States: Effect of population characteristics
Authors: Stehr‐Green Jeanette K. , Jason Janine M. , Evatt Bruce L.
Published: February 2007

National AIDS surveillance suggests that approximately 3.5% of all hemophilic patients in the United States have developed AIDS as of February 1988; however, the cumulative incidence of AIDS among seropositive patients at individual hemophilia treatment centers (HTCs) has been reported to be as high as 12%. The purpose of this study was to examine the reported excess risk of AIDS at selected HTCs. Between July 13 and November 6, 1987, we reviewed medical charts from the 598 hemophilia A and hemophilia B patients receiving comprehensive care as of 1980 at six U.S. hemophilia treatment centers (three identified as low AIDS risk and three identified as high AIDS risk using national hemophilia‐associated AIDS surveillance data). The risk of AIDS among all patients was 8% and among seropositive patients was 18%. At the individual HTCs, the risk ranged from 0% to 14% among all patients and 0% to 25% among seropositive patients. Overall incidence rates were higher than those derived from national surveillance data because national estimates include all hemophilic patients (regardless of severity) whereas this study included only patients receiving comprehensive care (who are more likely to be severely affected by their coagulation disorder and receive concentrated clotting factors). The higher incidence of AIDS in the high‐risk centers was attributable to the older age of the patients in these HTCs, a factor previously associated with an increased risk of AIDS in seropositive patients. These findings do not support geographic variability in the incidence of AIDS and emphasize the importance of patient characteristics when comparing the incidence of hemophilia‐associated AIDS between populations.
Multiple responses of aplastic anemia to low‐dose cyclosporine therapy despite development of a myelodysplastic syndrome
Authors: Litzow Mark R. , Kyle Robert A.
Published: February 2007

A 55‐year‐old white woman presented in July 1984 with severe aplastic anemia refractory to anti‐thymocyte globulin, corticosteroids, and danazol. In December 1984, oral cyclosporine therapy was begun, and a partial remission was achieved with persistent thrombocytopenia and transfusion independence. The cyclosporine dosage was tapered and then stopped in May 1986 when the platelet count was 35,000/L. In October 1986 the platelet count was only 16,000/L, and the bone marrow showed evidence of a myelodysplastic syndrome; cytogenetic analysis revealed deletion of the long arm of chromosome 13 (previous cytogenetic findings had been normal). After cyclosporine therapy was resumed, platelet count promptly increased to 36,000/L. A subsequent attempt to taper the cyclosporine dosage resulted in a decreased platelet count. The platelet count responded to cyclosporine again and was maintained at 54,000/L and higher with cyclosporine therapy at only 25 mg/day. This information suggests that, despite the development of a myelodysplastic syndrome, immune mechanisms were still operative in the pathogenesis of our patient's thrombocytopenia. Immune modulation may have an important role in preventing progression of myelodysplastic syndromes to more severe forms or to acute leukemia.
Inappropriate increase in erythropoietin titers during chemotherapy
Authors: Piroso Ettore , Erslev Allan J. , Caro Jaime
Published: February 2007

Serial erythropoietin measurements by RIA were performed in six patients with acute leukemia treated by intensive chemotherapy. In all cases erythropoietin titers increased after the onset of treatment, although the hemoglobin concentration remained at stable values. Subsequently the erythropoietin titers gradually returned to baseline levels. In same patients this reduction occurred at the end of chemotherapy, in others coincident with infections and antibiotic therapy. In four patients this decrease occurred at the time of bone marrow recovery.

The explanation for this inappropriate increase in erythropoietin titers is not clear but may be related to a direct or indirect effect of a suppressed marrow on sites of erythropoietin production or catabolism.
Severe hyponatremia after repeated intravenous administration of desmopressin
Authors: Weinstein Ralph E. , Bona Robert D. , Altman Arnold J. , Quinn John J. , Weisman Steven J. , Bartolomeo Ann , Rickles Frederick R.
Published: February 2007

Desmopressin (DDAVP) has recently been found to improve hemostasis in patients with congenital or acquired disorders of coagulation and to reduce operative blood loss in patients with normal hemostasis undergoing certain surgical procedures. Despite its potent antidiuretic effect, severe hyponatremia after the intravenous administration of DDAVP is felt to be rare. We report four cases of severe hyponatremia with serious clinical sequelae occurring in patients with underlying coagulopathies who were treated prophylactically with DDAVP to improve hemostasis prior to surgical procedures. Each patient received multiple (3–22) doses of DDAVP and was given intravenous hydration with hypotonic solutions before developing clinical signs and laboratory evidence of hyponatremia. We believe that the risk of significant hypoantremia after treatment with intravenous DDAVP may be higher than is generally appreciated and that patients undergoing surgical procedures, who often receive multiple doses of DDAVP and intravenous hydration, are at particular risk for this complication. Hypotonic intravenous solutions should be avoided and serum sodium levels should be monitored frequently in those patients receiving multiple doses of DDAVP.
Two‐year evaluation of clinical and laboratory variables of immune function in 117 hemophiliacs seropositive or seronegative for HIV‐1
Authors: Teitel Jerome M. , Freedman John J. , Garvey M. Bernadette , Kardish Margaret
Published: February 2007

Fifty‐nine HIV‐1 antibody positive and 58 antibody negative hemophiliacs were evaluated over a 2 year study period to gain insight into the natural history and prognosis of HIV‐1 disease in members of this risk group. Mean CD4 (Leu 3+) cell counts calculated at 6 month intervals decreased gradually in seropositive patients (from 403 to 311/μl), whereas CD8 (Leu 2+) counts remained stable but above the normal range. CD4 cell counts correlated closely with advancing CDC clinical stage; CD8 numbers showed no such association, but were markedly lower in the six patients with overt AIDS. Serum P24 antigenemia was associated with low CD4 cell counts and with advanced clinical stage (58% of antigenemic and 14% of non‐antigenemic seropositive patients were in stage IV). In addition to CD4 cell counts, significant reductions in Leu 11+ natural killer cell (NK) subsets and in Leu 3+8‐ cells occurred in seropositive patients over the study period; Leu 2 + DR+ cells increased significantly. When expressed as a percentage of lymphocytes, the reduction in Leu 19+ NK cells was also significant, as were the increases in Leu 4 + DR+ cells and Leu 12+8+ B cells. In summary, declining CD4 cell numbers and percentages are valuable markers of progressive HIV‐1 disease in hemophiliacs, but may not always accurately reflect the degree of disease activity. Progressive changes in additional variables such as serum P24 antigen, and numbers and percentages of NK cell subsets and (as AIDS supervenes) CD8 cell numbers, may allow more precise monitoring of HIV‐1 disease. This will, in turn, facilitate the design of optimal individualized strategies for therapeutic intervention.
Natural killer lymphocyte blast crisis of chronic myelogenous leukemia
Authors: Warzynski M. J. , White C. , Golightly M. G. , Steingart R. , Otto R. N. , Podgurski A. E. , Johnson M. L. , Glynn P. , Smith D. E.
Published: February 2007

We describe for the first time a case report documenting a chronic myelogenous leukemia (CML) patient who developed a blast crisis of natural killer (NK) lymphocytes. Many of the blasts exhibited large granular lymphocytic (LGL) morphology. Single parameter immunophenotyping results determined that the granulated as well as the agranulated blast cells were NK lymphocytes (CD45, NKH1, CD2, LEU 17, and CD16 positive; CD3, CD8, and LEU 7 negative). Dual parameter flow cytometric testing also determined that some of the blasts expressed the CD11b and CD11c markers as reported for some types of NK lymphocytes. Approximately 10% of the cells were in the S phase of the cell cycle as determined by a modified Vindelov DNA content analysis test and may theoretically reflect some of those cells expressing CD11b and CD11c. The cells did not express in vitro NK lymphocyte functional activity against a K562 target and therefore similar to other reported cases of presumably immature NK lymphocytic leukemias. The NK lymphocyte blast crisis was successfully treated with vincristine and prednisone. The patient's disease eventually relapsed and transformed to a progenitor stem cell before she died (CD45, 13, CD38, and CD34 positive). The flow cytometric immunophenotyping results contributed significantly as an important adjunct in determining the appropriate diagnosis, helping to select the type of therapy, and monitoring the patient with this unusual type of blast crisis.
Hemoglobin Villejuif [β 123(H1) Thr→lle]: A new variant found in coincidence with polycythemia vera
Authors: Wajcman H. , Mrad A. , Blouquit Y. , Parmentier C. , Riou J. , Galacteros F.
Published: February 2007

A new abnormal hemoglobin, Hb Villejuif [β 123 (H1) Thr→IIe] has been discovered during the exploration of a polycythemia in a 87‐year‐old patient of French origin. The isoelectric focusing of the lysate revealed the presence of a variant hemoglobin with an isoelectric point very close to that of HbA. The oxygen binding properties of the patient's red blood cells being normal, it was clear that the polycythemia was not a consequence of the presence of this hemoglobin. In fact, the red blood cell morphology and the involvement of the other blood cell lines, demonstrating excessive hemopoiesis, led to the diagnosis of polycythemia vera.
Hereditary sideroblastic anemia with associated platelet abnormalities
Authors: Soslau Gerald , Brodsky Isadora
Published: February 2007

A 62 year old male (R.H.) presented with a mild anemia (Hb 11–12 gm%) and a history of multiple hemorrhagic episodes. The marrow had 40–50% sideroblasts. Marrow chromosomes were normal. His wife was hematologically normal, while one daughter, age 30 years, had a sideroblastic anemia (Hb 11–12 gm%) with 40–50% sideroblasts in the marrow. Her anemia was first noted at age 15 years. Administration of vitamin B6 did not correct the anemia in either the father or daughter. Platelet abnormalities inherited jointly with this disorder are described for the first time. Both R.H. and his daughter had prolonged bleeding times, with normal PTT, PT times, fVIII:C, fVIII:Ag levels, and vWF multimers, which may rule out a von Willebrand's disease. They have normal platelet numbers but abnormally low platelet adhesiveness and greatly depressed ADP, collagen, and epinephrine responsiveness. Response to ristocetin was in the low normal range, and aggregation with thrombin was normal. While desmopressin completely normalized R.H.'s bleeding time, none of these platelet parameters were improved. No differences in the SDS PAGE protein patterns of RH platelets could be detected in comparison to normal samples. His platelets took up and released serotonin (5HT) normally, and electron micrographs defined no morphological abnormalities. However, no ATP was released from platelets activated with collagen, and when followed by thrombin about fourfold greater ATP was released by control platelets as compared to RH platelets. The dense granule fraction derived from RH platelets contained about 20% the level of ATP, 40% the level of ADP, and 50% the level of 5HT detected in a normal sample. The results indicate that the bleeding disorder is related to a non‐classical heritable storage pool defect. The connection between the inherited sideroblastic anemia and platelet defects is obscure.
Nonsecretory multiple myeloma in a 26‐year‐old man with acquired immunodeficiency syndrome, presenting with multiple extramedullary plasmacytomas and osteolytic bone disease
Authors: Karnad Anand B. , Martin Alvin W. , Koh Howard K. , Brauer Mark J. , Novich Marilyn , Wright Jonathan
Published: February 2007

High grade B‐cell lymphoma and leukemia have been well described in patients with the acquired immunodeficiency syndrome (AIDS). Malignant transformation of more differentiated lymphoid cells has not been well described in these patients. We report a 26‐year‐old man with AIDS‐associated multiple myeloma, who had a highly unusual presentation and clinical course. A review of the literature indicates that monoclonal gammopathy in patients seropositive for the human immunodeficiency virus (HIV) is common. Multiple myeloma and extramedullary plasmacytomas, diseases that are extraordinarily rare in young persons, are now being reported in patients with AIDS and should be added to the list of neoplastic diseases now associated with HIV infection.
Procollagen type III aminoterminal peptide in serum in idiopathic myelofibrosis and allied conditions: Relation to disease activity and effect of chemotherapy
Authors: Hasselbalch H. , Junker P. , Hørslev‐Petersen K. , Lisse I. , Bentsen K. D.
Published: February 2007

The serum concentration of the aminoterminal propeptide of type III procollagen (PIIINP) was measured serially in patients with idiopathic myelofibrosis and other myeloproliferative syndromes. Two different assays were applied, the RIA‐gnost assay (Hoechst, Frankfurt, FRG) and a new equilibrium RIA for the N‐terminal propeptide of human type III procollagen (Farmos Diagnostica, Oulu, Finland).

A positive correlation was found between the results obtained by the two RIA's (rho = 0.90. P < 0.001). The highest propeptide levels were recorded in patients with idiopathic myelofibrosis, particularly in those with active disease. Elevated serum PIIINP levels decreased during treatment with various cytotoxic drugs, including intensive chemotherapy. By contrast, serum PIIINP was unchanged or increased in patients undergoing interferon alpha‐2b therapy.

Gel filtration of sera on Sephacryl S‐300 column (Pharmacia, Sweden) showed that smaller PIIINP related peptides dominated in healthy subjects and in osteomyelosclerosis with stable disease. Conversely, the relative proportion of intact propeptide increased in accelerating disease stages and acute myelofibrosis.

In conclusion, the present study implicates serum PIIINP as a useful indicator of disease activity in idiopathic myelofibrosis. The propeptide also appears to be a sensitive sero‐marker of chemotherapy effect on fibrogenesis related to clonal myeloproliferation. Finally, the propeptide is suggested as an early predictor of relapse during cytotoxic therapy.
Intranuclear inclusions in myeloma cells in a case of nonsecretory multiple myeloma
Authors: Feng Chi‐Shun
Published: February 2007

Inclusions in the nucleus, compared with those in the cytoplasm, are rare in myeloma cells but have been reported in all electrophoretic varieties of multiple myeloma except the nonsecretory type. In this unusual case, a 54 year old Chinese woman had a pathological fracture of the left femur, and biopsy of the fracture site revealed a round cell tumor compatible with plasmacytoma. A bone marrow aspirate revealed 50% plasma cells, many of which contained intranuclear inclusions. Protein electrophoresis was normal with no paraprotein, and urine was free from Bence‐Jones protein. Under electron microscopy, the plasma cells showed electron‐dense spherules not circumscribed by a membrane. The absence of a membrane was unusual, because according to all reported cases, these intranuclear inclusions were invariably membrane‐bound. The association of nonsecretion of paraprotein in myeloma, which is rare, and the absence of a membrane enclosing the intranuclear inclusions, which is heretofore unreported, is probably not coincidental but causally related in that paraprotein produced in the nucleus of myeloma cells (stored in the form of intranuclear inclusions) fails to be detected in serum and urine because of noninteraction between these inclusions and the membranes of the nucleus and endoplasmic reticulum.
Acute pancreatitis complicating therapy of Hodgkin disease: A case report
Authors: Batson Oliver A. , Branda Richard F.
Published: February 2007

Acute pancreatitis developed in a young woman with disseminated Hodgkin disease coincident with cytotoxic treatment. Despite concerns about possible drug‐related causes, chemotherapy was continued without further gastrointestinal consequences. This case indicates that pancreatitis need not necessarily alter therapeutic plans for Hodgkin disease. Causes of pancreatitis in the setting of malignancy are reviewed.
Deficient elevation of the cytoplasmic calcium ion concentration by epinephrine in epinephrine‐insensitive platelets of patients with myeloproliferative disorders
Authors: Ushikubi Fumitaka , Okuma Minoru , Ishibashi Takafumi , Narumlya Shuh , Uchino Haruto
Published: February 2007

Elevation of the cytoplasmic Ca2+ concentration ([Ca2 +]i) by epinephrine and epinephrine‐induced inhibition of prostaglandin E1 (PGE1)‐stimulated cyclic adenosine monophosphate (CAMP) accumulation were assessed in platelets from three groups of subjects: normal controls (NS, n = 11) and patients with myeloproliferative disorders whose platelets were either sensitive (ES, n = 9) or specifically insensitive (El, n = 7) to the aggregatory effect of epinephrine. The inhibition by epinephrine of CAMP accumulation in the platelets exposed to 500 nM PGE, was not significantly different between the three groups. Therefore, despite the detective aggregation response to epinephrine, platelets from the El group seemed to retain normal response, which was attained through cα2‐adrenergic receptors, guanine nucleotide binding regulatory protein, and the adenylate cyclase system. However, in aequorin‐loaded, washed platelets, the epinephrine‐stimu‐lated rise in [Ca2+]i showed significant decrease in the El group compared with the other groups (P < 0.01). Thus the mechanism for the impaired aggregation response to epinephrine in platelets from the El group could include the defect that exists in the pathway from receptor binding of epinephrine to the aggregation response through [Ca2+]i elevation.
Prevalence of a shortened prostacyclin half‐life in plasma in healthy adults: Results of a screening investigation
Authors: Sinzinger H. , Rauscha F. , Fitscha P. , Granegger Susanne
Published: February 2007

Out of a total of 1,981 adults (956 males, 1,025 females; aged 16‐71 yr) undergoing a screening investigation for elevated cholesterol only 3 healthy participants with pathologically enhanced prostaglandin 12 (PG12) degradation in plasma in vitro were discovered. The PG12 half‐life in these three screenings was shorter than 60 sec and persisted during several follow‐up checks. In one patient a familial defect was discovered. Diseases known to be associated with this disturbance in PG12 metabolism have been excluded. The mean half‐life of PG12 in 1,978 people amounted to 10.71 ± 1.93 min. It still needs to be clarified whether this rare disturbance in PG12 metabolism is causally related to, or only associated with, thromboembolic events. A possible predisposition should be elucidated by regular monitoring of affected persons.
Stimulation of myelopoiesis in chronic lymphocytic leukemia and in other lymphoproliferative disorders by recombinant human granulocyte‐macrophage colony‐stimulating factor
Authors: Vadhan‐Raj Saroj , Velasquez William S. , Butler James J. , Lemaistre Anne , Lepe‐Zuniga Jose , Keating Michael J. , Koller Charles A. , Gutterman Jordan U.
Published: February 2007

In an attempt to stimulate granulopoiesis, we administered recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) to 11 patients with lymphoprolif‐erative disorders. Ten patients had neutropenia, six of whom had severe neutropenia (<500 neutrophils), including two with agranulocytosis. GM‐CSF (60‐250 μg/m2/day) was administered by continuous intravenous infusion daily for 14 days at 2‐week intervals. Significant increases in white blood cell counts (1.3‐ to 11.7‐fold) and neutrophils (1.7‐ to more than 29‐fold) were seen in 10 of 11 patients, including one patient with agranulocytosis. Eosinophils (3.9‐ to > 65‐fold) and monocytes (1.3‐ to >5‐fold) increased as well. In contrast, no significant increases were seen in total lymphocytes or in different phenotypic subsets of lymphocytes during treatment. The overall proportion of myeloid and lymphoid elements in bone marrow remained stable. These results indicate that GM‐CSF is effective in stimulating myelopoiesis in neutropenic states associated with lymphopro‐liferative disorders. Further studies will be necessary to determine whether the correction of neutropenia ultimately translates into clinical benefit.
The transferrin receptor system is not involved in the pathogenesis of hematological disorders with 3q inversion
Authors: Abe Yasunobu , Muta Koichiro , Yufu Yuji , Takahira Hiroyuki , Nishimura Junji , Nawata Hajime
Published: February 2007

To clarify the idea that an alteration of the transferrin receptor (TF‐R) gene, localized to 3q26, may be of pathogenetic significance in hematological disorders with 3q anomaly, we studied the TF‐R systems of erythroblasts from both functional and genetic aspects. The patient described here had refractory anemia with an excess of blasts (RAEB), with paracentric inversion, inv(3)(q21q26). The patient had the characteristic findings of mi‐ cromegakaryocytosis and thrombocytosis, with giant platelets. There was no functional abnormality of TF‐R as far as number of binding sites, affinity, molecular weight, or recycling kinetics were concerned. Furthermore, we could not recognize any rearrangement of the TF‐R gene with Southern blot analysis. These data suggest that TF‐R is not involved in the pathogenesis of leukemogenesis and thrombocytosis of the disease.
Reduced serum haptoglobin values in hemophiliacs receiving monoclonally purified factor viii concentrates
Authors: Buchanan George R. , Holtkamp Christine A. , Johnson Andrea
Published: February 2007

Hemophiliacs often have mild anemia, and hemolysis has been suggested as the likely mechanism on the basis of the reduced serum haptoglobin values frequently observed in these patients. It has been suggested that hypohaptoglobinemia results from isohemagglutinins or other contaminating proteins in the infused factor concentrates. The advent and increased utilization of Factor VIII concentrates that are highly purified by use of monoclonal antibodies have provided the opportunity to study whether proteins other than Factor VIII contained in the concentrate induce hemolysis. Of 49 consecutively studied Factor VIII‐deficient hemophiliacs, 19 (39%) had a reduced serum haptoglobin level (< 27 mg/dl). In particular, 16 of 35 (46%) of patients receiving only monoclonally purified Factor VIII products (Monoclate or Hemofil‐M) had a reduced serum haptoglobin value. Haptoglobin measurements were variable on repeat measurement in 8 patients. Haptoglobin levels did not correlate with type or severity of hemophilia, hemoglobin value, or alterations in liver function. Low serum haptoglobin values were also observed in children with leukemia, without apparent hemolysis, who had extensive cutaneous hemorrhage associated with thrombocytopenia. We propose that reduced serum haptoglobin values in hemophiliacs do not result from immune‐mediated hemolysis due to contaminating proteins in the concentrate. Moreover, hypohaptoglobinemia may not be due to hemolysis at all but may instead result from dissolution of hematomas and other foci of internal hemorrhage.
Successful treatment of hairy cell leukemia with β‐ser interferon
Authors: Wiernik Peter H. , Schwartz Bradford , Dutcher Janice P. , Turman Nancy , Adinolfi Crestina
Published: February 2007

Twelve patients with hairy cell leukemia underwent treatment with beta‐ser interferon, a type I interferon with potent antiproliferative activity. Ten of the 12 patients had had prior therapy and the median time from diagnosis to initiation of treatment was 8.5 months (range 1 month to 18 years). Bone marrow involvement ranged from 90‐100% hairy cells. Beta‐ser interferon was administered as an intravenous injection of 90 million units per dose, three times weekly. Dose reductions were by dose and by frequency in individual patients. Ten of 12 patients (83%) responded, including 7 complete (CR) and 3 partial (PR) responses. The median time to at least PR was 6 months and the median time to CR was 12 months. The median duration of overall response (PR + CR or PR) is 31+ months (range 26+‐40+ months). Of the 6 patients who underwent dose reductions due to toxicity or poor tolerance, 4 CR patients reverted to PR, and 2 PR patients have increased the number of hairy cells in the marrow, while maintaining normal peripheral blood counts. One each of these has regained CR and PR status after an increase in dose.
In vivo aging of red cell enzymes: Study of biotinylated red blood cells in rabbits
Authors: Zimran A. , Forman L. , Suzuki T. , Dale G. L. , Beutler E.
Published: February 2007

It is generally recognized that the activities of some of the red cell enzymes decline as the cell ages. However, there is still a controversy regarding the rate at which this aging occurs. In the present study we applied newly developed technology for the specific isolation of maturing reticulocytes/erythrocytes for a more comprehensive study of in vivo aging of red cell enzymes in rabbits. Anemia was induced by repeated phlebotomy, and reticulocyte‐rich erythrocytes were labeled with N‐hydroxy succinimido‐biotin and then transfused into a normal rabbit. These biotinylated cells were isolated at various time points by their affinity for an avidin support, and the enzymatic activity of 19 red cell enzymes was measured. We observed a biphasic pattern of decay for the activity of six age‐dependent enzymes—aldolase, glutamate‐oxaloacetate transaminase, glucose 6‐phosphate dehydrogenase, hexokinase, pyrimidine 5′‐nucleotidase, and pyruvate kinase.
Detection of engraftment and chimerism after bone marrow transplantation by in situ hybridization using a Y‐chromosome specific probe
Authors: Agematsu Kazunaga , Kitahara Fuminori , Uehara Yoshio , Kawai Hiroshi , Miyagawa Yukiaki , Komiyama Atsushi , Nakahori Yutaka , Nakagome Yasuo , Akabane Taro
Published: February 2007

After bone marrow transplantation (BMT), the recipient and donor cells must be distinguished from each other to document and characterize successful engraftment. In addition to dot blot and Southern blot analyses, we have performed in situ hybridization in two sex‐mismatched cases using a Y‐chormosome specific DNA probe (PHY10). In situ hybridization showed that >95% of the peripheral mononculear cells had clusters of grains indicative of male cell origin in a recipient girl (case 1), and no cells had clusters of grains in another recipient boy (case 2) at the time of engraftment and 3 months after BMT. In situ hybridization using the PHY10 probe appears to facilitate identification of individual cells of male and female origin, and it requires only 20 hr to obtain the results. The technique provides a powerful new method for the documentation of engraftment and the detection of mixed hematopoietic chimerism in peripheral blood and bone marrow cell compartments after BMT.
Treatment of patients with disseminated intravascular coagulation by protein C
Authors: Okajima Kenji , Imamura Haruo , Koga Shin , Inoue Masayasu , Takatsuki Kiyoshi , Aoki Nobuo
Published: February 2007

The therapeutic effect of highly purified protein C (PC) or activated protein C (APC) on three patients with disseminated intravascular coagulation (DIC) was tested. In two out of three cases, although therapeutic dose of heparin was not effective, PC or APC administration significantly improved the hypercoagulable state. In one case with acute leukemia who developed DIC with the severe gastrointestinal bleeding, APC corrected the hypercoagulable state without aggravating bleeding. These findings suggested that PC and/or APC might be effective in correcting hypercoagulable state without any adverse effect.
Treatment of pain in adults with sickle cell disease
Authors: Ballas Samir K.
Published: February 2007

The treatment of an adult patient with sickle cell disease whose clinical course is characterized by frequent painful crises creates a number of logistic problems in a tertiary care city hospital. Because such patients usually have no objective signs of painful crises, they are often considered to be malingerers and drug abusers. This paper reviews this controversial issue and presents one attempt at its resolution.
Phase II trial of α‐tocopherol (vitamin E) in the treatment of primary systemic amyloidosis
Authors: Gertz Morie A. , Kyle Robert A.
Published: February 2007

Primary systemic amyloidosis (AL) is a rare disorder characterized by deposition of a monoclonal immunoglobulin light chain or fragment thereof, resulting in dysfunction of the heart, kidney, liver, or nerves. Despite the use of melphalan, prednisone, colchicine, and dimethyl sulfoxide (DMSO), no improvement in median survival has been reported in prospective randomized studies.

We undertook a study of α‐tocopherol acetate (vitamin E) in the treatment of 16 patients with AL because of its reported benefits in animal models of senile and secondary amyloidosis as well as reported benefit in the treatment of secondary amyloidosis in humans. None of the patients showed any objective regression of their disease. The median survival of the entire group was 19.4 months. This survival is not superior to that reported with other agents used in this disease. We conclude that α‐tocopherol is not a valuable agent in the treatment of AL.
“idiopathic thrombocytopenic purpura‐like syndrome” treated with interferon in a patient with lung cancer
Authors: Rapoport B. L. , Falkson G. , Alberts A. S. , Eloff P.
Published: February 2007

A case of autoimmune thrombocytopenia associated with lung cancer is presented. The thrombocytopenia occurred 2 years before the diagnosis of lung cancer. Previous treatments include high doses of corticosteroids and splenectomy. The patient was managed with interferon, which resulted in an increase of the platelet count with control of the hemorrhagic manifestations with this syndrome.
Cobalamin as coenzyme: A twisting trail of research
Authors: Beck William S.
Published: February 2007

Cobalamin derivatives serve as coenzymes for the body's two cobalamin‐dependent enzymes—adenosylcobalamin‐dependent methylmalonyl CoA mutase, and methylcobalamin‐dependent methionine methyltransferase.

This essay reviews, in brief form and in personal terms, the history, beginning in the mid‐1950s, of how these enzymes and coenzymes were discovered and what has been learned of their reaction mechanisms. It is clear that because of the fragility of the unique carbon‐cobalt bond in Cobalamin coenzymes, they serve primarily as free radical formers. This accounts for their efficiency in abstracting hydrogen from substrate molecules and for a subsequent chain of events that results in the isomerization of methylmalonyl CoA, the transfer of methyl groups, and (in certain bacteria) the reduction of ribonucleotides. Some thoughts are offered on the possible evolutionary significance of these facts.
Histidine‐rich glycoprotein as a negative acute phase reactant
Authors: Saigo Katsuyasu , Yoshida Akinori , Ryo Ryukichi , Yamaguchi Nobuo , Leung Lawrence L. K.
Published: February 2007

Serum histidine‐rich glycoprotein was determined by the Laurell method in patients with acute inflammation, which negatively correlated with C‐reactive protein (P < 0.005). In sequential observations, this negative relationship was apparently confirmed. Thus histidine‐rich glycoprotein acts as a negative acute phase reactant.
Direct detection of β thalassemic mutations: Use of biotin‐labelled allele specific probes
Authors: Hendy J. G. , Cauchi M. N.
Published: February 2007

Mutations at positions βIVSS1–6, βIVS1–110, and β39 of the β globin gene are responsible for the three most common thalassemic genes in the Mediterranean population. The polymerase chain reaction (PCR) was employed to amplify a 536 base pair segment surrounding this region. Nonradioactive labelling of an oligonucleotide probe, specific for the βIVS1–110 mutation, was achieved by incorporation of biotin‐16‐dUTP into a standard 3′‐end labelling procedure. This probe was subsequently hybridized with the PCR amplification product and permitted detection of the mutant gene in a homozygous β thalassemic child by a simple colour detection method using a streptavidin‐alkaline phosphatase conjugate and NBT/BCIP (nitroblue tetrazolium/5‐bromo‐4‐chloro‐3‐indolyl phosphate) substrate. A known cloned mutant gene was similarly detected. Results could be obtained within 48 hr. These findings suggest that such an approach could provide a rapid and specific means for detection of β thalassemic mutations without the need for radioactive probes.
Structure of the granulocyte macrophage colony‐stimulating factor gene in patients with the myelodysplastic syndromes
Authors: Boultwood Jacqueline , Abrahamson Gail , Buckle Veronica J. , Rack Katrina , Oscier David G. , Wainscoat James S.
Published: February 2007

DNA samples from 76 patients with the myelodysplastic syndromes, including 10 cases with a partial deletion of the long arm of chromosome 5 (5q‐), were examined for structural rearrangements of the granulocyte/macrophage colony‐stimulating factor (GM‐CSF) gene. No abnormalities were detected, indicating that structural aberrations of this gene are not a feature of the myelodysplastic syndromes.
Excess of red cell membrane proteins in hereditary high‐phosphatidylcholine hemolytic anemia
Authors: Lane Peter A. , Kuypers Frans A. , Clark Margaret R. , Andrews Deborah A. , Wagner Gail M. , Butikofer Peter , Shapiro Amy D. , Chiu Daniel T. Y. , Lubin Bertram H. , Mentzer William C.
Published: February 2007

Previous descriptions of hereditary high‐phosphatidylcholine hemolytic anemia (HPCHA) have highlighted the association of increased erythrocyte membrane phosphatidylcholine with abnormal membrane cation permeability. We studied the function and composition of erythrocyte membranes from three individuals with HPCHA to characterize further the membrane abnormalities in this disorder. Despite significant macrocytosis, HPCHA red cells were dehydrated and showed an increased surface area to volume ratio compared to normal red cells. The passive efflux of K+ from HPCHA erythrocytes was increased fourfold at 37°C. Total membrane phospholipid was increased 7–42%, largely due to excess phosphatidylcholine, which made up 35.8–37.2% of total phospholipid. Membrane cholesterol:phospholipid ratios were in the normal range. It appears that the excess phosphatidylcholine was not acquired during circulation, since plasma lipids were normal and all subpopulations of density‐separated HPCHA erythrocytes were similarly abnormal. The ratio of total protein to phospholipid in white ghosts was increased, indicating that membrane protein was increased to an even greater extent than membrane lipids. No abnormal membrane proteins were identified by Coomassie or periodic acid Schiff (PAS) staining. Quantitation of the major membrane proteins indicated that the total protein excess in HPCHA membranes was due to a proportional increase in all major proteins. We conclude that HPCHA erythrocytes have excess membrane proteins and hypothesize that the changes in lipid composition and cation permeability are secondary to underlying protein abnormalities, which remain to be defined.