bluuebunny/crossref_metadata_2025 huggingface dataset:
Postleukemic dysmyelopoiesis
Authors: Foucar Kathy , Vaughan William P. , Armitage James O. , Patil Shivanand , Dick Fred , Karp Judith E.
Published: February 2007

The morphologic and clinical features of four patients who developed significant bone marrow and blood dyspoiesis after successful chemotherapy for acute nonlymphocytic leukemia (ANLL) are described. This postleukemic dyspoiesis developed 1‐6 months after leukemia induction therapy and persisted for 5‐20 months in a relatively stable state. This period of prolonged dyspoiesis was not associated with rising myeloblast counts or clinical evidence of relapse. Dyspoietic abnormalities developed while two patients were receiving maintenance chemotherapy; the other two patients received no maintenance therapy. The dyspoietic changes in these four patients greatly exceeded those noted in a control group of ANLL patients on maintenance chemotherapy. The morphologic features of postleukemic dysmyelopoiesis were similar to those described in preleukemic dysmyelopoietic disorders. Erythroid abnormalities included hyperplasia with ring sideroblasts, megalobalstic changes, and cytoplasmic PAS reactivity. Myeloid abnormalities consisted of left‐shifted granulopoiesis with hyper‐ and hyposegmentation; megakaryocytic abnormalities included hyperplasia with a predominance of hypolobulated forms. Three of the four patients eventually suffered relapse and have died. The fourth patient died of sepsis after 20 months of pancytopenia and hysmyelopoiesis. Theories to explain the development of postleukemic dysmyelopoiesis are presented which emphasize the possibility of drug‐induced leukemia cell differentiation. Cytogenetic studies will be necessary to establish any relationship between ANLL and the subsequent postleukemic dysmyelopoiesis.
Monocyte markers and the common acute lymphoblastic leukemia antigen on chronic lymphocytic leukemia cells
Authors: Ligler Frances S. , Schlam Mark L , Curley Robert , Brodsky Isadore , Benzel John E.
Published: February 2007

The mononuclear cells from 42 patients with chronic lymphocytic leukemia (CLL) were analyzed for surface markers using monoclonal antibodies and flow cytofluorimetry. All 42 CLLs were Ig+ HLA.DR+OKT3−OKT4−OKT6−OKT8− and monoclonal with respect to light chain type. Thirty of the 42 tumours expressed the common acute lymphocytic leukemia antigen, and cells from 18 leukemias stained with the antibodies OKM1 and 63D3, which are specific for different antigens characteristic of myeloid cells. Eight of the leukemias failed to stain with PI153, which has been reported to recognize all B‐cell CLLs.
Complement in thrombotic thrombocytopenic purpura
Authors: Garvey M. Bernadette , Freedman John
Published: February 2007

This report describes a patient with recurrent thrombotic thrombocytopenic purpura (TTP)in whom complement activation was observed during the acute episodes. Serum C3, C4, and CH50 were reduced, and there was deposition of C3 on red cells and platelets. These findings returned to normal during clinical remission.
Autologous marrow transplantation for patients with chronic myelogenous leukemia (CML) in blast crisis
Authors: Thomas M. Roy , Robinson William A. , Dantas Mary , Koeppler Hubert , Drebing Carla , Glode L. Michael
Published: February 2007

Eleven patients with chronic myelogenous leukemia (CML) in blast crisis were treated with chemotherapy, followed by infusion of autologous bone marrow that had been collected during the chronic phase of the disease and cryopreserved at −198°C. The mean age of the nine females and two males in this study was 34 years with an average duration of the chronic phase of the disease of 5.5 years. Seven out of the 11 patients had a splenectomy prior to intensive chemotherapy. The median survival of the first four patients who received 6‐thioguanine, cytosine arabinoside, daunorubicin (TAD) chemotherapy was 2.6 weeks and no patient reachieved the chronic phase of CML. The second group of seven patients received more intensive chemotherapy (MAdHAT), which included melphalan 30 mg/m2 days 1, 2, and 3; Adriamycin 50 mg/m2 intravenously (iv) day 1, hydroxyurea 1500 mg/m2 by mouth for 5–7 days, cytosine arabinoside 100 mg/m2 continuous infusion for 5–7 days, and VM‐26 100 mg/m2 iv on day 3. Six out of these seven patients reachieved chronic phase CML after bone marrow reinfusion. The median survival was 29.9 weeks for all patients and 33 weeks for the six patients who reachieved chronic phase CML. All patients subsequently died of recurrent blast crisis. There was no correlation between the time of bone marrow storage and the duration of subsequent chronic phase CML. These studies have shown that autologous bone marrow transplantation after high‐dose chemotherapy can result in bone marrow engraftment with reestablishment of chronic phase CML, and prolongation of survival.
Difference between young and old patients in characteristics of leukemic cells: Older patients have cells growing excessively in vitro, with low antigenicity despite high HLA‐DR antigens
Authors: Giannoulis Nicos , Ogier Claudio , Hast Robert , Lindblom Bertil , Sjögren Ann‐Marie , Reizenstein Peter
Published: February 2007

Fifty‐six patients with acute, nonlymphatic leukemia in the initial phase were studied. The poor prognostic signs were excessive in vitro growth, many HLA‐DR‐positive cells, or a low ratio of leukemic cell antigenicity to HLA‐DR positivity and age. The cells from older patients formed more clusters (P < 0.05), and they had less capacity to stimulate normal allogeneic lymphocytes (P < 0.05) than those from younger patients. Cells forming many clusters also were more often (P < 0.01) HLA‐DR‐positive than those forming few clusters. It is suggested that the prognosis in old patients with acute leukemia is poor in part because their leukemic cells have characteristics different from those of young patients.
Myocardial infarction in sickle cell anemia
Authors: Barrett O'Neill , Saunders Donald E. , McFarland Dee E. , Humphries J. O'Neal
Published: February 2007

A review of the electrocardiograms (ECG) of 108 patients with sickle cell anemia found only 3 with patterns consistent with myocardial infarction. Two of the 3 patients with ECG infarct patterns had postmortem examination confirmation of the infarction. These two patients had no significant coronary atherosclerosis nor did the other six autopsied patients in the present series. Literature reports of postmortem examinations on patients with sickle cell anemia confirm the scarcity of coronary atherosclerosis and myocardial infarction in these patients.

Forty of the 108 ECGs showed signs of left ventricular hypertrophy and 20 others had nondiagnostic ST and T wave abnormalities. Nine showed first degree AV block and four right bundle branch block.
T cells and erythroid burst forming units in chronic lymphocytic leukemia
Authors: Socinski Mark A. , Ershler William B.
Published: February 2007

Substantial evidence exists indicating T cell abnormalities in chronic lymphocytic leukemia (CLL). There is also evidence that the T cell is an important source of burst promoting activity (BPA) for the peripheral blood (PB) erythroid burst forming unit (BFU‐e). We studied the BPA of T cells and response of BFU‐e in normals and untreated early stage B cell CLL patients in a methylcellulose colony assay. Normal null cell cultures grew significantly more BFU‐e than CLL null cell cultures. Addition of autologous T cells to normal or CLL null cells significantly increased BFU‐e only in normals. Allogeneic coculture of T cells from CLL patients with null cells from normals yielded normal responses of BFU‐e in five of six cases. In contrast, allogeneic coculture of normal T cells with CLL null cells yielded a normal response in only one of six studies. Furthermore, adding increasing quantities of autologous or normal allogeneic T cells to CLL null cells did not augment the BFU‐e response. Accounting for the expanded lymphocyte pool in CLL, BFU‐e are decreased in concentration but the absolute number is normal or increased. The decrease in concentration could be secondary to expansion of the null cell fraction in CLL by pre‐B cells. CLL T cells appeared to augment normal allogeneic PB BFU‐e in a normal fashion, whereas, in several cases, CLL BFU‐e were hyporesponsive to autologous or normal allogeneic T cells. It is therefore apparent that in untreated early stage B cell CLL, erythroid progenitor cells are present in the peripheral blood but are diluted in an expanded null cell compartment and may, in some cases, be hyporesponsive to T cell BPA. T cell BPA of CLL T cells in this early stage of disease is preserved.
The relation of megakaryocyte ploidy to platelet volume
Authors: Bessman J. David
Published: February 2007

To determine how alterations of megakaryocyte proliferation will affect platelet production, we measured mean platelet volume (MPV), platelet volume heterogeneity, platelet count, and mean megakaryocyte ploidy in 42 patients. In normal subjects, mean platelet volume and megakaryocyte ploidy were related inversely but nonlin‐early to platelet count, whereas mean platelet volume and platelet volume heterogeneity were related directly. In patients with immune thrombocytopenic purpura (low platelet count, MPV above normal, and increased megakaryocyte ploidy), and in those with reactive thrombocytosis (high platelet count, low MPV and megakaryocyte ploidy), the relation of MPV to megakaryocyte ploidy, platelet volume heterogeneity, and platelet count resembled or extended the relations found in normal subjects. By contrast, in patients with aplastic anemia or megaloblastic anemia, or in patients who were undergoing chemotherapy for leukemia, heterogeneity was increased abnormally at any MPV, and both MPV and megakaryocyte ploidy were substantially lower, at any platelet volume, than in normals or the above other groups. The most common ploidy class was 8N in all patients, and the mean megakaryocyte ploidy correlated directly and linearly with mean platelet volume. The data show that bone marrow with megakaryocytes of higher ploidy produces platelets that are both larger and more heterogeneous.
Procainamide‐induced thrombocytopenia
Authors: Rosenstein Robert , Kosfeld Rodney E. , Leight Leonard , Liu Yong K.
Published: February 2007

An 81‐year‐old female developed marked thrombocytopenia associated with numerous megakaryocytes in the bone marrow, but without anemia or leukopenia, after taking procainamide (3 g/day) for a period of 2 months. Despite continuation of this medication, treatment with prednisone led to rapid rise in platelet count, and withdrawal of steroid was followed by prompt recurrence of thrombocytopenia. The platelet counts returned to normal after discontinuation of procainamide, and read‐ministration of this drug was followed by reappearance of thrombocytopenia. These observations indicate that exposure to procainamide can cause isolated thrombocytopenia, probably due to immune‐mediated destruction of platelets, and that treatment with prednisone may be promptly beneficial in patients with procainamide‐induced severe thrombocytopenia and bleeding.
Changes in coagulation parameters with exercise in patients with classic hemophilia
Authors: Koch Barbara , Luban Naomi L. C. , Galioto Frank M. , Rick Margaret E. , Goldstein David , Kelleher John F.
Published: February 2007

Vigorous exercise is known to increase VIII:C and VIIIR:Ag levels transiently in normal individuals. Although exercise programs are frequently advocated in the management of hemophilia, the effects of exercise on coagulation parameters in these patients have not been well studied. Eleven hemophiliacs were exercised on a bicycle ergometer to maximum voluntary effort as evidenced by an increase in pulse, blood pressure, and plasma catecholamine (norephinephrine and epinephrine) levels. The effects of this exercise on coagulation parameters, including functional and antigenic components of the factor VIII molecule, were determined.

The entire group demonstrated a decrease in mean prothrombin time (11.7 to 11.2 sec). Four mild hemophiliacs demonstrated an increase in mean VIII:C (14.5% to 17.3%), and VIII:CAg (12% to 17.8%). Changes in VIII:C and VIII:CAg were not noted in the seven severe hemophiliacs. Both severe and mild patients demonstrated significant changes in fibrinogen, factor II, and factor VII after exercise. This study indicates that submaximal exercise modifies coagulation parameters in patients with hemophilia.
Two successful pregnancies in a woman with chronic thrombotic thrombocytopenic purpura treated by plasma infusion
Authors: Lian Eric C.‐Y. , Byrnes John J. , Harkness Donald R.
Published: February 2007

A 21‐year‐old primigravida in her 20th week of pregnancy developed TTP. She was managed with weekly or semiweekly plasma infusions and delivered a healthy 1.6 kg baby 2 weeks prior to the expected date of delivery. After delivery she continued to have active TTP with thrombocytopenia which responded repeatedly to plasma infusion though their frequency gradually decreased to about one unit every 3–4 weeks. Three years after the birth of the first child she conceived again and was easily managed with repeated plasma infusions although the frequency and amount of plasma required to prevent thrombocytopenia were increased. She delivered a normal 3.4 kg term baby after which she again had a decreased plasma requirement.

This is the first report of a woman with 5 years of active TTP managed with plasma alone. She experienced two pregnancies in which both mother and infant survived. We believe that the use of plasma in the management of TTP during pregnancy will improve the survival rate of both mother and infant.

At the time of second birth, the platelet count was low in the mother but normal in the baby. This suggests that the platelet depressing factor of this patient does not cross the placental barrier.
Infectious complications in 127 patients with hairy cell leukemia
Authors: Golomb Harvey M. , Hadad Laura J.
Published: February 2007

Information regarding infectious complications was obtained on 127 patients with hairy cell leukemia who were diagnosed between March 1974 and April 1982. Forty‐seven patients (37%) had 111 documented infections (cultures positive), and 40 patients (31.5%) had 113 nondocumented infections (no culture results available, or cultures negative). The remaining 40 patients (31.5%) had no significant infections during the course of their disease. Patients without infection lived significantly longer than did patients who developed an infection (92% v 49% were alive at 4 years; P = .0012). Thirty‐three of the 47 patients with documented infection have died; 29 of an infectious problem and four of a noninfectious problem. There was also a statistically significant difference in actuarial survivals between the documented‐infection and nondocumented infection groups (P = .007). The two most common types of infection were bacteremia (30 episodes) and pneumonia (27 episodes). In the culture‐documented group with bacteremia, E coli and P aeruginosa caused ten and eight infections, respectively, and three infections were due to S aureus. There were eight systemic infections of nonbacterial origin; in five, the organism cultured was M kansasii, and three were fungal infections. Blood counts at the time of diagnosis were not correlated with subsequent development of infection. Patients with hairy cell leukemia have a significant susceptibility to infections that can affect morbidity and mortality. Many of the infectious complications encountered are those common in patients whose immune system is compromised; however, the occurrence of disseminated atypical mycobacterial disease requires a heightened awareness.
Migration of porcine endothelial and smooth muscle cells in response to platelet‐associated factors
Authors: Gee Adrian P. , Minta J. O.
Published: February 2007

A NeuroProbe multiwell microchemotaxis assembly has been used to study the migration of porcine aortic endothelial and smooth muscle cells in vitro in response to serum factors. Whole pig serum was found to be chemokinetic for endothelial cells but not smooth muscle cells. Chemokinetic activity was higher in platelet‐enriched, plasma‐derived serum (PDS) than in platelet‐free PDS. The supernatant from washed, lysed pig platelets also showed chemokinetic activity both for endothelial and smooth muscle cells. Chromatography on Sephadex G‐200 showed that the lysate contained a number of activities that act independently on the two cell types. The chemokinetic activity that we have detected appears to be distinct from the chemotactic effect of platelet‐derived growth factor and platelet factor 4 on the basis of insensitivity to protamine sulfate and molecular size. The role of these platelet factors in pathological changes in vascular structure is currently under study.
Quantitation of hemoglobin components by high‐performance cation‐exchange liquid chromatography: Its use in diagnosis and in the assessment of cellular distribution of hemoglobin variants
Authors: Kutlar Abdullah , Kutlar Ferdane , Wilson Jerry B. , Headlee Marsha G. , Huisman Titus H. J.
Published: February 2007

Additional data are presented that were obtained with a newly developed cation‐exchange high‐performance liquid chromatography (HPLC) method allowing the separation of numerous normal and abnormal human hemoglobin types. The method was found to be of considerable value for the diagnosis of certain hemoglobinopathies in the adult as well as in the newborn. Definitive differentiation between, AS, SS, S‐β+‐thal, SD, SC, AC, C‐β+‐thal, etc in cord bloods was readily accomplished even when the samples were collected on filter paper.

Analyses of the hemoglobin in cells from Hb S and Hb C heterozygotes with different numbers of α chain genes (αα/αα; ‐α/αα; ‐α/α) after separation by a Dextran density centrifugation technique failed to show significant changes in the relative quantitation of the variant hemoglobin types. Glycosylalation of hemoglobin increased greatly with an increase in red cell age. Similar analyses of red cells from a young girl with Hb S trait and Hb H disease (the ‐/α genic arrangement) gave comparable data. Some indication was obtained that her youngest cells contained some of the βA4 and βS4 tetrameric hemoglobins.
Erythrocyte sensitization with monomeric IgM in a patient with hemolytic anemia
Authors: Szymanski Irma O. , Huff Sara R. , Selbovitz Leslie G. , Sherwood Geoffrey K.
Published: February 2007

An automated antiglobulin test showed that erythrocytes of a patient with an acute episode of Coombs‐negative hemolytic anemia were strongly sensitized with nonagglutinating IgM molecules. The bound antibodies, after elution from red blood cell stroma, were found to be monomeric IgM, since they migrated with IgG molecules on an agarose column, although they were proved to be immunoglobulin M, not G, by a sensitive hemagglutination inhibition assay.

The hemolysis subsided with steroid therapy, but ANA increased to a titer greater than 1,024 (with peripheral pattern) without other laboratory evidence of systemic lupus erythematosus. In addition, the patient demonstrated photosensitivity and non‐scarring alopecia. We consider that this appearance of erythrocyte autoantibodies consisting of monomeric IgM was a symptom of atypical SLE.
Red cell CDP (dCDP)‐choline and P‐choline in normal subjects and in certain hemolytic syndromes
Authors: Valentine William N. , Jenden Donald J. , Paglia Donald E.
Published: February 2007

The concentrations of red cell CDP (dCDP)‐choline and P‐choline were measured and compared in normal subjects, in subjects with hemolytic anemia other than that due to pyrimidine‐5′‐nucleotidase deficiency, in homozygotes for the latter enzymopathy, and in a single subject with a hemolytic syndrome speculatively due to choline phosphotransferase deficiency.
Enhancement of adenosine 3′,5′‐monophosphate in human mononuclear and polymorphonuclear leukocytes by snake venoms
Authors: Stolc Viktor
Published: February 2007

Snake venoms contain compound(s) that enhanced cyclic AMP content in human mononuclear leukocytes maximally after 5 min of incubation at 37°C. The effect was time‐ and dose‐dependent. The half‐maximal stimulation of cyclic AMP production by black cobra venom was found at 0.45 μg of venom/ml and the value of the Hill coefficient was 0.7. The black cobra venom enhanced the cyclic AMP content in the cells at 4, 22, and 37°C. Similar increase in the cyclic AMP content by six snake venoms was found in human polymorphonuclear leukocytes. The most active venom was from puff adder (Bitis arietans). The data suggest that one of the effects of the snake venoms may be rapid enhancement of cyclic AMP level in the affected cells.
Abnormalities of lymphocyte subsets are correlated with concentrate consumption in asymptomatic Italian hemophiliacs treated with concentrates made from American plasma
Authors: Mannucci P. M. , Gringeri A. , Ammassari M. , Mari Daniela
Published: February 2007

Eighty‐three symptom‐free hemophiliacs were studied clinically, serologically, and by in vitro tests for cellular immunity in a geographical area in which AIDS has not yet been encountered despite the exclusive use of concentrates manufactured from American sources of plasma. Some patients showed the following abnormalites: lymphopenia (4%), decreased T‐helper/T‐suppressor (Th/Ts) cell ratios (49%), or both abnormalities (2%). Low Th/Ts were mostly due to absolute or, less frequently, relative increases in Ts cells. The prevalence rates for these abnormalites were the same in patients treated with factor VIII or factor IX concentrates. There was an association between the higher Ts and lower Th cells counts and the low Th/Ts ratios and greater annual consumption of factor VIII and factor IX concentrates. These results support the view that protein load might be an important pathogenetic factor in lymphocyte abnormalities in symptom‐free hemophiliacs.
A method for the separation of erythrocytes on the basis of size using counterflow centrifugation
Authors: Thompson Craig B. , Galli Rachel L. , Melaragno Anthony J. , Valeri C. Robert
Published: February 2007

A method has been developed for separation of erythrocytes on the basis of size using counterflow centrifugation. Human red blood cells with an original mean corpuscular volume (MCV) of 89.2 ± 4.1 fl were isolated, free of plasma proteins and other cell contaminants, into seven fractions ranging in size from 77.0 ± 2.7 fl to 98.5 ± 4.8 fl. The ratio of the age‐related enzyme, erythrocyte glutamic oxaloacetic transferase (EGOT), to hemoglobin (Hb) increased progressively through the fractions, suggesting a correlation between erythrocyte volume and age. Reticulocytes, though present in all fractions, were selectively enriched in the larger subpopulations.

To verify the biochemical evidence that erythrocytes decrease in volume with aging, in vivo cohort labeling of red blood cells with 59Fe was performed in baboons. A similar relationship of EGOT to Hb was observed to that in the human subpopulations. The peak activity of 59Fe/RBC appeared initially in the red blood cells with the highest MCV and progressed from the erythrocytes with the largest MCV to the erythrocytes with the smallest MCV over the next 10–12 weeks, confirming the hypothesis that red blood cells decrease in volume as they age. The technique of counterflow centrifugation appears to provide a simple, rapid, and reproducible method for the separation of erythrocytes on the basis of size.
Aplastic anemia complicating systemic lupus erythematosus: Response to androgens in two patients
Authors: Stricker Raphael B. , Shuman Marc A.
Published: February 2007

We describe two female patients with systemic lupus erythematosus (SLE) who developed severe aplastic anemia. Although each patient had received multiple medications including diphenylhydantoin, the relationship of these drugs to the development of marrow aplasia was unclear. After administration of an oral androgen (oxymethalone) and corticosteroids, there was complete hematologic recovery. Both patients relapsed when oxymethalone was withdrawn, and both recovered when androgen therapy was reinstituted, with or without high‐dose prednisone. In both patients, there was complete reversal of pancytopenia despite the presence of initially severe marrow aplasia (less than 10% cellularity). However, in both cases, prolonged androgen therapy (2 months) was required before hematologic improvement occurred. Androgens are known to stimulate hematopoiesis in man, and they appear to influence immune function in a mouse model of SLE. Thus androgens may be particularly useful in the treatment of SLE‐associated aplastic anemia.
Cimetidine suppression of CFU‐C in males
Authors: Gross Samuel , Worthington‐White Diana A.
Published: February 2007

A presumed cimetidine‐induced granulocytopenia in a 6‐year‐old male with acute lymphocytic leukemia (ALL) prompted an investigation of the effects of cimetidine on in vitro bone marrow granulocyte colony growth (CFU‐C) in normal individuals and ALL patients either on maintenance chemotherapy or off all therapy for at least 1 year. The addition of cimetidine resulted in a significant reduction of colony numbers as compared to untreated controls beginning at 1 × 10−6 M (P < 0.05) and increasing in significance as the concentration of cimetidine increased. Analysis of sex differences showed that CFU‐C derived from females were not adversely affected by the addition of cimetidine (except at levels far in excess of recommended dosages) whereas CFU‐C in males declined significantly from controls beginning at 1 × 10−7 M (P < 0.05) and became of greater significance as the concentration of cimetidine increased. These findings were identical for both normal individuals and ALL patients either receiving maintenance chemotherapy or off all therapy.
Effect of heparin on platelet aggregation
Authors: Saba H. I. , Saba S. R. , Morelli G. A.
Published: February 2007

The effect of heparin on platelet aggregation was systematically examined on platelets in plasma (PRP), as well as on gel‐filtered, washed, and formaldehyde‐fixed platelets. Results indicate that, although heparin causes a mild potentiation of platelet aggregation in the PRP systems, a significant inhibitory activity is observed when heparin is added to isolated platelets. This inhibitory activity appears to be specific and not related to the impurities in the heparin preparations, as heparinase, as well as protamine, effectively neutralizes the heparin‐mediated inhibitory activity on platelet aggregation.

Although heparin‐mediated inhibitory activity can be demonstrated in the presence of a number of different agonists (ADP, arachidonic acid, thrombin, Ionophore A23187, epinephrine, and ristocetin), the most pronounced inhibition is seen in the presence of ristocetin. Further studies show that heparin enhances thrombox‐ane generation in isolated platelets. Platelets pretreated with heparin, however, fail to respond to preformed thromboxane. These findings suggest that, in addition to the potentiation of thromboxane production in platelets, heparin may also attribute some change(s) to the platelet(s)/platelet membrane, which interferes with their ability to respond to the agonists of platelet aggregation. This antiaggregatory activity of heparin was found to be inhibited by a factor(s) present in plasma but not in serum.
Efficacy of several plasma components in a young boy with chronic thrombocytopenia and hemolytic anemia who responds repeatedly to normal plasma infusions
Authors: Miura Masayoshi , Koizumi Shoichi , Nakamura Katsuji , Ohno Takashi , Tachinami Tomoko , Yamagami Masahiko , Taniguchi Noboru , Kinoshita Seiji , Abildgaard Charles F.
Published: February 2007

This report describes a patient with thrombocytopenia, microangiopathic hemolytic anemia, proteinuria, and microscopic hematuria that could be transiently improved by the infusion of plasma or various plasma components. An increase in platelet count following the transfusion of normal plasma was predictable and reproducible. In therapeutic trials with commercially available plasma components, factor VIII preparations were effective for inducing an increase in the platelet count and improving hemolytic anemia, but albumin, γ‐globulin, factor IX, and fibronectin preparations were ineffective. Serum from normal donors also relieved the symptoms of this condition in our patient. Partial plasma exchange (1,000 ml/m2 of body surface area) was performed with albumin instead of normal plasma, but there was no significant effect on platelet count or anemia. Large, multimeric von Willebrand factor components of the factor VIII complex (VIII/vWF) were found in the patient's plasma when his platelet count was normal, but their levels were reduced when the platelet count was decreased. The multimers of the patient's plasma were larger than those in normal plasma, but smaller than those in normal platelet lysate. Although the patho‐genesis of this disease remains unknown, we conclude that transfusions of normal plasma, serum, or factor VIII concentrate provide a factor that causes significant improvement in the thrombocytopenia and hemolytic anemia. Furthermore, large VIII/vWF multimers are possibly directly involved in pathogenesis of this disease.
Spontaneous disappearance of an IgA anti‐factor IX inhibitor in a child with christmas disease
Authors: Carroll Robert R. , Panush Richard S. , Kitchens Craig S.
Published: February 2007

The few inhibitors to blood coagulation factor IX in patients with Christmas disease (hemophilia B) that have been studied have been shown to belong to the IgG class of immunoglobulins. We report the first case in which a factor IX inhibitor was of the IgA class. Additionally, he appears to be the youngest patient with hemophilia B to have developed an inhibitor. His inhibitor complicated treatment of the patient for several years because of its anamnestic rise following factor IX concentrate administration. It then spontaneously vanished and has not returned in spite of repeated factor IX complex administration.
Treatment of polycythemia vera with hydroxyurea
Authors: Donovan Paul B. , Kaplan Manuel E. , Goldberg Judith D. , Tatarsky Ilana , Najean Yves , Silberstein Edward B. , Knospe William H. , Laszlo John , Mack Karen , Berk Paul D. , Wasserman Louis R.
Published: February 2007

Conventional treatment of polycythemia vera (PV) with radioactive phosphorus or alkylating agents is associated with a significant excess of acute leukemia and cancer of the gastrointestinal tract and skin. There is thus a need for a nonmutagenic agent in the treatment of this disorder. Hydroxyurea (HU) was administered to 118 patients with a loading dose of 30 mg/kg/day for 1 week, which was then reduced to 15 mg/kg/day. Initial control of the elevated hematocrit and platelet count was achieved within 12 weeks in over 80% of patients. Long‐term disease control was defined and the accumulative 1‐year failure‐free survival was 73% in the previously untreated patients and 59% in those patients previously treated with other myelosuppressive modalities. The HU was well tolerated and cytopenia, which generally occurred within the first 8 weeks of therapy, was transient and of little clinical significance. However, it is recommended because of this toxicity that HU be administered initially at a dose of 15‐20 mg/kg/day. Three patients developed acute leukemia; two were untreated and one had had myelosuppressive therapy. Hydroxyurea is an effective agent in the treatment of PV, but continued assessment of its mutagenic potential is necessary.
Differentiation of chronic lymphocytic leukemia cells after in vitro treatment with epstein‐barr virus or phorbol ester. I. Immunologic and morphologic studies
Authors: Deegan Michael J. , Maeda Koichi
Published: February 2007

Leukemic cells from ten patients with “nonsecretory,” B‐type chronic lymphocytic leukemia (CLL) were cultured alone or in the presence of Epstein‐Barr virus (EBV) or a phorbol ester (12‐0‐tetradecanoylphorbol‐13‐acetate; TPA) for 7 days. At periodic intervals the cell morphology, cytoplasmic immunoglobulin content (direct immunofluorescence) and capacity for immunoglobulin secretion (hemolytic plaque assay) were assessed. A variable but significant number of the TPA‐treated CLL cells from all patients expressed cytoplasmic immunoglobulin of a single light‐chain type at some stage, usually within the first 3 days. EBV induced similar changes in seven of eight cases tested. Untreated cell cultures were negative or contained a few cytoplasmic immunoglobulin‐positive cells. Cells from five of nine cases secreted immunoglobulin of a single light‐chain type. In every instance this was identical to the surface and cytoplasmic immunoglobulin. Cytologic changes were observed in the leukemic cells after treatment with one or both agents in nine of ten cases. The major feature was an increase in cell size associated with immunoblastic or plasmacytoid features. Mitotic figures and binucleate cells were also present. These studies indicate that EBV and TPA are effective at inducing immunoglobulin synthesis and secretion in “nonsecretory” B cell neoplasms and are useful tools for studying the maturation potential inherent in these tumors. The study also suggests that the secreted immunoglobulin is a monoclonal product.
Heparin‐induced thrombocytopenia: A prospective study
Authors: Johnson Robert A. , Lazarus Kenneth H. , Henry David H.
Published: February 2007

Thrombocytopenia is a well‐described complication of heparin therapy. Few studies describe the incidence of thrombocytopenia when low‐dose heparin (10,000–15,000 units/day) is used for prophylaxis of deep venous thrombosis. In our study, ten of 66 courses (15%) of heparin prophylaxis in coronary care unit patients were accompanied by a mild thrombocytopenia with platelet counts below 150 ± 103/mm3. In all cases the platelet count returned to normal despite continued heparin therapy. Patients who became thrombocytopenic had significantly lower initial platelet counts. No cases of severe thrombocytopenia were seen (platelet count below 100 ± 103/mm3). No patient developed thrombosis, bleeding or elevated fibrin split products. Mild thrombocytopenia occuring after 2–5 days of low‐dose heparin is common, but clinically insignificant.
Pharmacokinetics and tolerance of intravenous and intramuscular recombinant alpha2 interferon in patients with malignancies
Authors: Shah I. , Band J. , Samson M. , Young J. , Robinson R. , Bailey B. , Lerner A. Martin , Prasad A. S.
Published: February 2007

Fifteen patients with advanced hematopoietic and other malignancies were treated with recombinant DNA produced Alpha2 Interferon (IFN) (Schering) by intravenous (IV) and intramuscular (IM) routes at weekly intervals in escalating doses from 1 × 106 IU to 100 × 106 IU in order to determine the tolerance and pharmacokinetics. The most common side effects included fever, chills, myalgia, and arthralgia. At doses of 60 × 106 or above, severe but reversible hypotension was observed in five patients receiving interferon by intravenous route. Patients receiving interferon by intramuscular route had fever, chills, and myalgias but did not develop hypotension at the same dosage. Two patients with non‐Hodgkin lymphoma showed objective evidence of regression. Our data suggest a biphasic pattern of elimination with terminal half‐life ranging from 1.9 to 2.9 hours and peak titer of 16,000 units and under for IV interferon, and terminal half‐life of 6 hours with peak titers of 600 units for intramuscular interferon. However, interpatient variability precludes a definite conclusion.

Although the areas under the serum concentration vs time curves were similar, the intravenous route provided higher but unsustained levels of interferon than the intramuscular route.
Preparation of low‐affinity red cells with dimethylsulfoxide‐mediated inositol hexaphosphate incorporation: Hemoglobin and ATP recovery using a continuous‐flow method
Authors: Franco R. S. , Wagner K. , Weiner M. , Martelo O. J.
Published: February 2007

Incorporation of IHP into red cells decreases oxygen affinity as a result of the binding of this compound to the 2,3‐DPG site of hemoglobin. This investigation describes a continuous‐flow method which utilizes the osmotic pulse technique to transport IHP into RBC. Using this procedure, it is possible to obtain a significant increase in P50 while maintaining in vitro cellular integrity. For example. IHP incorporation sufficient to cause an increase in the P50 of 20 mm Hg may be achieved with recovery of approximately 75% of the hemoglobin and with maintenance of ATP levels compatible with good viability. The continuous‐flow method allows uniform treatment of large, unit‐size volumes of red cells with a relatively small quantity of reagents. The final cell product is macrocytic/hypochromic with an increased number of stomatocytes.
Thrombotic thrombocytopenic purpura: Clinical course and response to therapy in eight patients
Authors: Evans Terry L. , Winkelstein Alan , Zeigler Zella R. , Shadduck Richard K. , Mangan Kenneth F.
Published: February 2007

The clinical manifestations, pathologic findings, and responses to therapy were reviewed in eight patients with thrombotic thrombocytopenia purpura (TTP). Only one exhibited all five cardinal manifestations; five showed a triad of anemia, thrombocytopenia, and neurologic abnormalities. Microangiopathic red cell changes on peripheral blood smear and severe thrombocytopenia were present in all. The serum LDH levels were initially elevated in all eight; this enzyme determination was extremely useful for following the course of the disease and its response to therapy. Pathologic evidence of TTP was most consistently found in lymph nodes, spleen, and bone marrow biopsies. All patients were treated with a combination of therapeutic modalities including plasma exchange with replacement by fresh frozen plasma. Using this approach, 7/8 entered a complete remission; however, disappearance of all clinical manifestations was not seen in two patients prior to splenectomy.
Membrane expansion as a mechanism explaining the antisickling action of ticlopidine observed in vitro
Authors: Sablayrolles Magali , Wajcman Henri , Castaigne Jena‐Paul , Labie Dominique
Published: February 2007

Ticlopidine, a platelet antiaggregant, has shown some efficacity in a clinical trial in patients with sickle cell disease. We have studied this agent in vitro to evaluate its effects on sickle erythrocyte. Ticlopidine effects sickling in vitro not by direct interaction with hemoglobin, but via strong binding to the red cell membrane. The density of the whole cell population is decreased when cells are treated with 0.1 mM ticlopidine, which is higher than the concentrations of 1 μM potentially achievable in vivo. Since hemoglobin concentration influences the delay time for gelling, its decrease in the red cell could have a beneficial effect. Such a partial inhibition of the polymerization is shown by oxygen equilibrium studies at various ionic strengths.
Changes in cellular ferritin content during myeloid differentiation of human leukemic cell lines
Authors: Fibach Eitan , Konijn Abraham M. , Rachmilewitz Eliezer A.
Published: February 2007

The human promyelocytic cell lines HL‐60 can be induced to undergo differentiation to either granulocyte‐ or macrophagelike cells. We followed the changes in the synthesis and content of ferritin in this and other cell lines during differentiation. Ferritin content of HL‐60 cells ranged from 11 to 81 fg/cell, depending on the clone tested. Following exposure to dimethylsulfoxide (DMSO) or retinoic acid (RA) an increase in ferritin and a decrease in total protein synthesis was observed, resulting in increased ferritin content, reaching a peak after 2 days. This increase occurred prior to the appearance of the typical morphological and functional characteristics of mature granulocytes. A correlation was found between concentrations of DMSO effective in inducing differentiation and the increase in ferritin content. Other inducers of granulocyte differentiation had a similar effect, while 12‐0‐tetradecanoylphorbol‐13‐acetate (TPA), an inducer of macrophage differentiation, had not. Another human cell line (U‐937), which was induced into monocytelike cells by RA, showed a twofold increase in ferritin content following differentiation. Addition of iron to the culture medium increased ferritin content of both differentiating and nondifferentiating cells, but the former responded to lower concentrations of iron. The increase in ferritin during differentiation, however, was not related to an accelerated iron uptake. The present results suggest that changes in the intracellular ferritin of the developing myeloid cells may play a regulating role in the process of maturation of these cells.
Evidence for two isozymes of leukocyte alkaline phosphatase in leukemic leukocytes
Authors: Miller Donald M. , Yang Angela , Liepman Marcia
Published: February 2007

Leukocyte alkaline phosphatase (LAP) is a granulocyte enzyme whose level of expression is markedly altered in various disease states. We have characterized LAP from normal cells and leukemic cells with a high level of LAP activity in order to determine whether increased enzyme levels are caused by increased levels of the same enzyme or induction of a different alkaline phosphatase.

Leukocyte alkaline phosphatase was purified from normal granulocytes and from leukemic cells of a patient with chronic granulocytic leukemia (CGL) in blast phase with an elevated LAP level. LAP was partially purified utilizing diethylaminoethyl (DEAE)‐cellulose ion exchange chromatography, gel filtration, and preparative electrophoresis.

The sample prepared from normal granulocytes contained a single protein with LAP activity having a molecular weight of 61,000 as determined by SDS gel electrophoresis. The sample from the CGL blast‐phase cells, however, demonstrated two proteins with alkaline phosphatase activity, one with a molecular weight of 61,000 (LAPs) and one with a molecular weight of 45,000 (LAPf). Differential heat inactivation and distinct isoelectric points of the two isozymes suggest that they are different proteins.

We interpret our data to suggest two closely related LAP alleles whose expression is controlled independently. This may represent either genetic heterogeneity or induction of “tumor marker” gene expression.
Spurious thrombocytopenia produced by the interaction of rheumatoid factor with antiplatelet antibody
Authors: Poskitt Thomas R. , Poskitt Paula K. F.
Published: February 2007

A patient had spurious thrombocytopenia resulting from a mechanism not previously described. Whereas in prior reports the in vitro phenomenon of platelet clumping has been effected by either EDTA‐dependent or temperature‐dependent antibodies capable of direct platelet agglutination, neither the IgG nor the IgM fractions of this patient's serum demonstrated such activity. However, agglutination was produced by incubating allogeneic platelets with the IgG fraction followed by a room temperature incubation with the rheumatoid factor‐positive IgM fraction. The data support a new mechanism for spurious thrombocytopenia resulting from the interaction of a cold‐reactive rheumatoid factor with antiplatelet antibody.
Platelet activity in mitral valve prolapse: A study of platelet aggregation, malondialdehyde production, and plasma β‐thromboglobulin
Authors: Arocha Francisco , Diez‐Ewald Maria , Durango Ana I. , Sulbarán Tulio
Published: February 2007

Platelet aggregation, malondialdehyde (MDA) production, and recovery after aspirin (ASA) administration and plasma levels of beta‐thromboglobulin (BTG) were determined in 40 asymptomatic patients with mitral valve prolapse (MVP) and 17 normal subjects. Platelet aggregation was similar in patients and controls, although two patients presented spontaneous aggregation. Production of MDA and plasma levels of BTG were higher in MVP than in controls; however, recovery after ASA was similar in both groups. The results further indicate that platelet hyperactivity is present in a significant number of asymptomatic patients with MVP.
A marked increase of calcium uptake in the ATP‐depleted red cells of patients with iron deficiency
Authors: Shimoda Masaoo , Yawata Yoshihito
Published: February 2007

Calcium (Ca) uptake was markedly increased in ATP‐depleted red cells of patients with iron deficiency anemia (IDA) compared to ATP‐depleted normal red cells. The extent of increased Ca uptake was related to the severity of iron deficiency as judged by decreased mean cell volume. Moreover, the increased Ca uptake returned to normal levels after oral iron supplementation therapy. The net calcium content of fresh red cells from iron‐deficient individuals was the same as in red cells from normal subjects. Sodium influx and ferric ion uptake appeared to be virtually unaffected in the iron deficient red cells.
Low molecular weight iron in guinea pig reticulocytes
Authors: Pollack Simeon , Campana Theresa , Weaver Janet
Published: February 2007

The low molecular weight iron found in the guinea pig reticulocyte has been partially characterized. On thin layer chromatography it is distinguishable from the iron complexes of a variety of nucleotides, sugars, and amino acids. On paper chromatography it comigrates with a 250‐nm absorbing, orcinol‐positive material. The eluted count peak contains phosphorus. Approximately 1 μg of iron is recovered from 1 ml of hemolyzed red cells. Preparation under nitrogen improves recovery of low molecular weight iron, suggesting that the iron is in the ferrous oxidation state.
The procoagulant effect of zinc on fibrin clot formation
Authors: Marx Gerard , Eldor Amiram
Published: February 2007

The influence of Zn+2 on fibrin clot formation was investigated by measuring its effect on the clotting times of fibrinogen exposed to thrombin. It was observed with either human or bovine thrombin that 0.01‐0.1 mM Zn+2 induced significant reductions of clotting times in a concentration‐dependent manner. The procoagulant effect of Zn+2 occurred in the presence of Ca+2 but was inhibited by metal chelating agents. Higher levels of Zn+2 (> 0.2 mM final concentration) were required to accelerate thrombin‐induced clot formation in the presence of citrate or oxalate. Similarly with oxalated human plasma, > 0.2 mM Zn+2 decreased the clotting time. Cations such as Mg+2 and Mn+2 caused little change in clotting times. As an extension of these findings, we examined the effect of Zn+2 on the in hibition of thrombin by antithrombin‐III (AT‐III). The presence of as little as 0.006 mM Zn+2 in an incubating mixture of thrombin and AT‐III severely reduced the inhibitory activity of AT‐III towards thrombin. It was observed that the relative intrinsic fluorescence emission of human thrombin decreased upon exposure to Zn+2 but was unaffected by Mg+2 or Mn+2. It is suggested that Zn+2 can form a complex with thrombin, which results in altered reactivity towards fibrinogen and decreased inhibition by AT‐III.