bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibers, crystals, and other forms of HbS polymers in deoxygenated sickle erythrocytes
Authors: Kaperonis Athanasia A. , Handley Dean A. , Chien Shu
Published: February 2007

We have examined by electron microscopy the formation of fibers and crystals from sickle hemoglobin within sickle erythrocytes following deoxygenation during capillary storage from 1 to 132 days. Intracellular fibers were found on the first day and throughout the period of study. The fibers exhibited a diameter (mean ± SD) of 17.4 ± 0.62 nm and were aligned in the cell with a fiber‐to‐fiber spacing of 18.6 nm (x‐axis) by 22.7 nm (y‐ axis). Between 65 and 132 days, extracellular hemoglobin crystals developed, with a lattice periodicity of 9.63 ± 0.6 nm. Fibers and crystals coexist as separate structures. These results suggest that crystal formation upon storage of packed deoxygenated sickle erythrocytes may proceed via a phase of fiber dissolution followed by hemoglobin reassembly into extracellular crystals, rather than by a progressive alignment and direct fusion of existing fibers.
The effect of Hb F and α‐thalassemia on the red cell indices in sickle cell anemia
Authors: Milner Paul F. , Garbutt George J. , Nolan‐Davis L. V. , Jonah Felix , Wilson Lois B. , Wilson John T.
Published: February 2007

This study examines the effect of different levels of fetal hemoglobin (Hb F) and the presence or absence of genes for α‐thalassemia on the red cell indices and degree of anemia among 102 patients with homozygous sickle cell disease (S/S) between the ages of 15 and 62 years. Patients were divided into those with an average Hb F of < 10 gm/L („low”︁ Hb F group) and those with > 10 gm/L („high”︁ Hb F group). α‐Thalassemia was assessed by restriction enzyme analysis of DNA by the Southern blotting technique. Homozygosity for the βs gene was confirmed by restriction enzyme analysis of DNA using the enzyme Mst II.

There were 51 patients with four α‐globin genes, 28 of whom had „high”︁ and 23 „low”︁ Hb F levels. Fifty‐one patients had α‐thalassemia, 38 of whom were heterozygous and 13 homozygous for the 3. 7 kb α‐thalassemia deletion. Nine had „high”︁ and 31 had „low”︁ Hb F. Irrespective of α‐globin genotype, patients in the high Hb F group had a higher mean Hb, Hct, MCV, and MCH than those in the low HB F group. In patients without α‐thalassemia Hb F was positively correlated with MCV and MCH (p < 0.001), patients with high Hb F levels having macrocytosis confirmed by microhematocrit studies. Patients with α‐thalassemia had a lower MCHC than patients with four α‐globin genes and this was not significantly affected by the level of Hb F. The combination of α‐thalassemia and high levels of Hb F appears to result in a distinctive S/S phenotype that is similar to the type of S/S disease described in Southern India.
Congenital thrombotic disorders
Authors: Rodgers George M. , Shuman Marc A.
Published: February 2007

The investigation of kindreds with recurrent thrombotic disease has advanced the understanding of the mechanisms of coagulation and fibrinolysis. In those cases where an etiology has been established, congenital thrombotic disorders are associated either with deficiencies or qualitative abnormalities in inhibitors of activated coagulation factors, qualitative abnormalities of fibrinogen, fibrinolytic defects that impair clot lysis, or an inborn error of metabolism, homocystinuria. The etiologies of congenital thrombotic disorders, their clinical features, and an approach to their laboratory diagnosis are summarized in this review.
In vivo study of lactoferrin and murine rebound myelopoiesis
Authors: Poppas Athena , Faith Michael R. , Bierman Howard R.
Published: February 2007

Lactoferrin has been reported to inhibit the production of colony‐stimulating factor (CSF); thus we sought to study its possible effects on myelopoiesis in vivo.

The characteristics of rebound myelopoiesis in C57BL mice injected with a sublethal dose of cyclophosphamide (CY) were used to test lactoferrin for any granulopoietic activity. An experimental group received daily injections of 50 μg of human lactoferrin beginning 24 hr after CY injections. By measuring the total nucleated cellularity of the femoral marrow, the peripheral blood count, and the incorporation of tritiated thymidine by the marrow in six replicate experiments, no statistically significant difference was noted between the lactoferrin injected groups and the control groups. Neither the route of lactoferrin administration (i.v. or i.p.) nor the sex of the animal altered the myelopoietic recovery.

Lactoferrin had no stimulatory or inhibitory effect on murine rebound myelopoiesis in vivo contrary to the reported in vitro results.
Cyclic neutropenia as a premalignant manifestation of acute lymphoblastic leukemia
Authors: Lensink Daniel B. , Barton Ann , Appelbaum Frederick R. , Hammond William P.
Published: February 2007

A 20‐year‐old female from the Philippines developed anemia and granulocytopenia. With androgen therapy, her anemia improved but she continued to show a pattern of fluctuating neutropenia consistent with human cyclic neutropenia: Blood neutrophil oscillation was regular with a periodicity of 21 days. She developed recurrent pharyngitis and apthous stomatitis but there was no cycling of other blood elements. Bone marrow aspiration and biopsy showed normal developing myeloid cells, a clonal chromosomal abnormality, and myelofibrosis. During the fourth documented cycle, blasts appeared and complete lymphoblastic transformation ensued. Blast cells were CALLA positive, Ia positive, and contained intranuclear TdT; they were negative for E, EAC, and EA rosettes. She was treated for non‐T, non‐B CALLA‐positive ALL and within 6 weeks was in a remission without evidence of cycling neutrophil counts. This young woman's case suggests that cyclic neutropenia may represent a previously unrecognized premalignant state associated with acute lymphoblastic leukemia.
Association of HLA and autoantibody in transfused sickle cell disease patients
Authors: Ofosu Mildred D. , Saunders David A. , Dunston Georgia M. , Castro Oswaldo , Alarif Lamya
Published: February 2007

This study evaluates autoantibody production in sickle cell disease patients and determines whether genes in the major histocompatibility complex are associated with autoantibody responses. Rheumatoid factor was significantly increased for both male and female patients and was less prevalent in highly transfused patients. Significant increases were also detected in the incidences of antinuclear antibody for females and antismooth muscle antibody for males. Low incidence of antinuclear antibody was significantly associated with HLA‐DR3. Significant associations were also found between the incidence of antinuclear antibody and both HLA‐A28 and B15.
Influence of HbS levels upon the hematological and clinical characteristics of sickle cell trait
Authors: Kennedy Alan P. , Walsh David A. , Nicholson Rosie , Adams Junius G. , Steinberg Martin H.
Published: February 2007

The variable concentration of HbS in individuals with sickle cell trait led us to study the relationship between HbS level and selected vascular events in 355 hospitalized black men with sickle cell trait. There were significant differences in hemoglobin concentration and mean corpuscular volume found in four groups divided by their HbS level, the lowest proportion of HbS (<30%) being associated with the lowest hemoglobin concentration (12.6 g/dl) and MCV (77 fl). The percent HbS did not influence the incidence of pulmonary embolism, thrombophlebitis, myocardial infarction, cerebrovascular accident, or idiopathic hematuria.

Our results suggest that HbS level does not influence vascular disease, and while certain hematological alterations occur, they are very unlikely to have any clinical significance. Regardless of the proportion of HbS, sickle cell trait in black men is benign.
Trisomy 1q in polycythemia vera and its relation to disease transition
Authors: Swolin B. , Weinfeld A. , Westin J.
Published: February 2007

Clinical and cytogenetic details of 12 patients with polycythemia vera and complete or partial trisomy of the long arm of chromosome 1 are reported. All patients had trisomy for at least the segments 1q22 to 1qter. The 1q or material from 1q was translocated to another chromosome in eight patients. This was chromosome 9 in four patients, and those cases all had trisomy also for 9p. The trisomy 1q was found at the time of diagnosis in three patients, later during the polycythemic phase in five, and in four patients when they were first examined during a late stage of the disease. Acute leukemia or a myelodysplastic syndrome developed in eight of the 12 patients. Signs of advanced disease, eg, myeloid metaplasia or myelofibrosis, preceded the leukemia in four cases and was noted in one more patient.

Trisomy 1q was the most frequent structural chromosome abnormality in patients with polycythemia vera. It is thus one of several nonrandom abnormalities that can appear at any stage of the disease. It seems to occur with higher frequency in patients with myelofibrosis and/or leukemia, but it is not a specific characteristic of these complications.
Primary amyloidosis (AL) in families
Authors: Gertz Morie A. , Garton John P. , Kyle Robert A.
Published: February 2007

We report the occurrence of immunoglobulin‐related amyloidosis (AL) in three separate families, each family having two members affected. None of the six patients had evidence to suggest the presence of familial amyloidosis (AF). Previously, immunoglobulin‐related amyloidosis (AL) was considered to be a sporadic disease process. Because of the occasional familial occurrence of other monoclonal gammopathies such as monoclonal gammopathy of undetermined significance, multiple myeloma, and macroglobulinemia of Waldenström, amyloidosis (AL) should be added to the list of immunopathies with a familial predisposition.
Philadelphia‐positive metaphases in the marrow after bone marrow transplantation for chronic granulocytic leukemia
Authors: Apperley Jane F. , Rassool Feyruz , Parreira Antonio , Geary Colin G. , Harrison Christine , Stansfield Derek , Goldman John M.
Published: February 2007

A 28‐year‐old man with Ph‐positive chronic granulocytic leukemia (CGL) was treated by high‐dose chemoradiotherapy and transplantation of marrow cells harvested from his HLA‐identical brother. One year after bone marrow transplantation (BMT) examination of his marrow showed a minority population of Ph‐positive cells; their proportion subsequently fell such that 2 years after transplant analysis of marrow cells showed only cytogenetically normal cells. The patient remains clinically normal with a persisting mild lymphocytosis but without hematological evidence of leukemia. We cannot in this patient distinguish between persisting leukemia that later could no longer be recognized and relapse of leukemia that is now suppressed, perhaps only temporarily. This case emphasizes the need for caution in interpreting chromosomal finding after BMT for CGL.
Leukapheresis for control of chronic myelogenous leukemia during pregnancy
Authors: Fitzgerald Denis , Rowe Jacob M. , Heal Joanna
Published: February 2007

Leukapheresis was used as the sole modality of treatment of a patient with chronic myelogenous leukemia (CML) during her pregnancy. The specific requirements for safe leukapheresis during pregnancy are discussed, and the literature describing the management of CML during pregnancy is reviewed. Leukapheresis may be the treatment of choice in selected pregnancy patients with CML since it avoids the potential teratogenic effects of chemotherapy or radiation therapy.
Frequency of α‐thalassemia in Greece
Authors: Kanavakis E. , Tzotzos S. , Liapaki A. , Metaxotou‐Mavromati A. , Kattamis C.
Published: February 2007

Using hematological and gene mapping techniques, a cord blood survey was carried out to estimate the frequency of α‐thalassemia in the Greek population. Out of 227 newborns studied, 16 (7.05%) were found by gene mapping to be α‐thalassemia 2 heterozygotes (‐α/αα), and of these only two had increased levels of hemoglobin Bart's in the cord blood (1.2 and 2.0%). Similarly, one heterozygote for the common Mediterranean α‐thalassemia 1 haplotype (–/αα) and one for the 20.5‐kb deletion type (‐α)20.5/αα) were found, showing increased levels of Bart's of 4.8 and 6.6%, respectively. Four (1.76%) heterozygotes for the triple α gene arrangement (ααα/αα) were found. One individual with a level of Bart's in the cord blood of 8% was found to be a double heterozygote for α‐thalassemia 2 and a dysfunctional α gene arrangement (‐α/‐(α)?). These results give an overall incidence for α‐thalassemia in the Greek population of 8.4%.
Antenatal diagnosis of β‐thalassemia by isoelectric focusing in immobilized pH gradients
Authors: Manca Mario , Cossu Gianfranco , Angioni Giuliano , Gigliotti Bruno , Bosisio Adriana Bianchi , Gianazza Elisabetta , Righetti Pier Giorgio
Published: February 2007

A new method for antenatal diagnosis of thalassemias is reported based on the analysis of the major Hb components of fetal cord blood, sampled at week 18 of pregnancy under ultrasonic guidance, by isoelectric focusing in immobilized pH gradients (IPG). In an IPG gel encompassing a pH 6.7–7.6 span, HbA and HbFac are separated by a distance nine times greater than in a conventional carrier ampholyte pH 6–8 gel and three times greater than in an ampholine gel with separators (an equimolar mixture of β‐alanine and 6‐amino caproic acid). Band evenness (in terms of uniform protein concentration within a zone) and straightness (in terms of parallel alignment of the bands to the electrodes), because of insensitivity of IPG gels to salt distortions, allows for accurate and reproducible quantitation of HbF, ‐A, and ‐Fac levels. The possibility of greatly overloading IPG matrices in total Hbs increases the sensitivity of the technique to the detection of only 0.5% HbA in the total Hb mixture, the lower limit of conventional IEF being only 2.5% HbA. Of 15 fetuses from couples at risk analyzed in the region of Ozieri, three were found to be homozygous β‐thalassemic, eight heterozygous, and four normal with no false‐positives or ‐negatives.
Busulphan versus combination chemotherapy for initial treatment of chronic granulocytic leukaemia
Authors: Jacobs Peter
Published: February 2007

In a pilot study, 21 consecutive and previously untreated adults with chronic granulocytic leukaemia received either busulphan (group 1: n = 11) or a combination of the epipodophyllotoxin VP16‐213 with cytosine arabinoside and doxorubicin (group 2: n = 10). Using a standardised protocol, objective response, defined as a granulocyte count consistently less than 10 × 109/1 with no clinical evidence of the disease, was achieved in 45 and 40% of the patients, respectively, and median survivals were 89 and 107 weeks (p > 0.05). Although there was no difference in morbidity, the study was discontinued because the combination chemotherapy was more complex to administer, was associated with greater patient inconvenience, and offered no advantage over single‐agent therapy in managing the stable phase of chronic granulocytic leukaemia.
Clinical utility of marrow cell tissue cultures in acute leukemia of childhood
Authors: Estrov Zeev , Grunberger Tom , Freedman Melvin H.
Published: February 2007

To determine the clinical value of tissue culture techniques in the study of acute leukemia, marrows from 50 children (40 acute lymphoblastic [ALL], 10 acute myeloblastic [AML]) were cultured by the use of an AML blast colony assay and the CFU‐GEMM assay. In the AML assay, AML marrow gave rise to high numbers of blast colonies within 24 to 48 hr; in sharp contrast, 37 of 40 ALL marrows did not yield colonies in this assay. In the CFU‐GEMM assay, AML marrow produced excessive numbers of monocyte‐macrophage CFU‐C colonies, an obvious background of individual macrophages and clusters, and occasional blast colonies. ALL marrow yielded very low numbers of granulocytic CFU‐C colonies, no background of macrophage cells, and no blast colonies. These clear‐cut differences in cellular growth kinetics in vitro between ALL and AML marrows should allow confirmation of the type of acute leukemia within 24 to 48 hr. The colony assays may also be valuable in differentiating ALL from AML in difficult diagnoses when conventional approaches are nondiagnostic.
Porphyria cutanea tarda in a patient with acute leukemia
Authors: Dutcher Janice P. , Fisher Michael , Spivack Morton , Wiernik Peter H.
Published: February 2007

A 20‐year‐old woman with acute nonlymphocytic leukemia in remission was treated postremission with intermittent courses of intensive chemotherapy. She required blood and platelet transfusions following therapy, and oral contraceptives were used to suppress her menses while she was thrombocytopenic. One and one‐half years after treatment began, she developed blisters on her hands, hypertrichosis, and dark urine. The diagnosis of porphyria cutanea tarda was made. This report discusses the possible precipitating cause(s) and the subsequent treatment of both her porphyria and her leukemia.
Platelet‐associated immunoglobulins IgG, IgM, IgA and complement C3 in immune and nonimmune thrombocytopenic disorders
Authors: Panzer Simon , Szamait Sabine , Bödeker Rolf‐Hasso , Haas Oskar A. , Haubenstock Alexander , Mueller‐Eckhardt Christian
Published: February 2007

A two‐stage radioactive antiglobulin test‐using unlabelled antisera specific for IgG, IgA, IgM and C3 followed by binding of 125I‐staphyloccocal protein A–was applied to determine platelet‐associated immunoglobulins (PAIg) and complement (PAC3) in thrombocytopenias of various etiologies. One hundred and one patients with immune thrombocytopenia (chronic autoimmune, 48; acute autoimmune, 37; Evans syndrome, nine; connective tissue diseases, seven) and 20 patients with presumed nonimmune thrombocytopenia (bone marrow aplasia or malignancy, six; septicemia, five; hypersplenism, five; cirrhosis of liver, three; others, one) were studied.

Increased levels of PAIg/C3 were found in 76% of patients with immune thrombocytopenia. PAIgG was raised in 66%, PAIgM in 57%, PAIgA in 44%, and PAC3 in 29%. Isolated elevation of PAIgG and of PAIgM was found in four and three cases, respectively; PAIgA and PAC3 were elevated in one case each. PAIgG was associated with PAIgM in 56%, with PAIgA in 34%, and with PAC3 in 27%. Both patients with Evans' syndrome and patients with connective tissue diseases had significantly higher PAIgM levels than the other patients with immune thrombocytopenia.

In patients with nonimmune thrombocytopenia, increased rates of PAIg/C3 were also encountered. Positive test results were found in 88% (PAIgG 88%, PAIgM 47%, PAIgA 35%, and PAC3 24%).

In immune‐mediated thrombocytopenia, we observed a significant inverse correlation between platelet counts and PAIgG, PAIgA, and PAC3, but not with PAIgM. In contrast, no such correlation was found in patients with nonimmune thrombocytopenia.

Our data indicate that the evaluation of neither parameter alone nor the combination of PAIg/C3 will discriminate between immune and nonimmune thrombocytopenia. Preferential coating with certain immunoglobulins, however, may be present in some subgroups of immune thrombocytopenias.
Spα1/65 hereditary elliptocytosis in North Africa
Authors: Alloisio N. , Guetarni D. , Morlé L. , Pothier B. , Ducluzeau M. T. , Soun A. , Colonna P. , Clerc M. , Philippe N. , Delaunay J.
Published: February 2007

The Spα1/65 variant of the spectrin has been recently described in black people with hereditary elliptocytosis (HE). The present study reports on a similar Spα1/65 variant in nine North African persons belonging to four unrelated families. The abnormality was associated with a variable degree of elliptocytosis. In one case, red cell morphology was normal. In the nine carriers of the biochemical abnormality, the spectrin dimer self‐association was defective. The association constant was reduced: 0.65 to 1.7 × 105 M−1 (controls: 4.6 × 0.5 × 105 m M−1 (n = 21)); in six cases, there was a higher level of spectrin dimer in the low ionic strength extract at 4°C: 13.0 to 19.7% (controls: 6.4 ± 2.1% (n = 7)). Limited tryptic digests of spectrin from the nine persons revealed a decrease of the 80,000‐dalton α‐1 domain, and the concomitant appearance of a peptide with a molecular weight of 65,000 daltons and an isoelectric point ranging from 5.0 to 5.1. There was a correlation between the proportion of the 65,000‐dalton fragments, the defect of spectrin self‐association, and the extent of morphological alteration. This is the first large series concerning a spectrin abnormality in non‐black persons. In North Africa, cases of HE that are not due to a protein 4.1 defect have turned out so far to be associated with the Spα1/65 variant.
Prednisone stimulation of erythropoiesis in leukemic children during remission
Authors: Amylon Michael D. , Perrlne Susan P. , Glader Bertil E.
Published: February 2007

Children with acute leukemia in remission manifest reticulocytosis and a significant increase in hemoglobin concentration (mean increment of 2.3 ± 1.1 g/d 1) following prednisone pulse therapy. This hemoglobin increment is not associated with changes in serum erythropoietin activity. It is speculated that this stimulation of red cell production may be a direct effect of steroids on erythroid progenitor cells.
Serum bactericidal and opsonic activities in chronic lymphocytic leukemia and multiple myeloma
Authors: Kansu Emin , Akalin Erdal , Civelek Cahid , Tekesin Oktay , Lalell Yahya , Firat Dinçer
Published: February 2007

Susceptibility to infection is widely recognized as the major cause of morbidity and mortality in patients with CLL and MM. The present study was designed to investigate the serum bactericidal (SBA) and serum opsonic activities (SOA) in 12 CLL and 12 MM patients, and results were compared to 20 normals. SBA and SOA were measured by a new radiometric assay. SBA was found to be normal in 11 patients with CLL and in all 12 patients with MM. In contrast, SOA was significantly lower in 11 out of 12 patients with CLL. Ten of twelve patients with MM also had significantly lower SOA compared to those of controls. No correlation was detected between the serum immunoglobulin and complement levels of the patients or between the degree of the opsonic defect and the incidence of infection. In mixture experiments, untreated normal serum partially corrected the opsonic activity of CLL and MM serum. The results suggest the presence of a possible inhibitor in the serum of patients with two well‐known B‐lymphocyte‐derived disorders.
Depletion of T lymphocytes from human bone marrow by the use of counterflow elutriation centrifugation
Authors: Takaue Yoichi , Roome Aaron J. , Turpin James A. , Reading Christopher L.
Published: February 2007

Normal donor bone marrow buffy coat (BMBC) cells were fractionated into three subsets by counterflow elutriation centrifugation. Fraction 1 (Fr‐1) was lymphocyteenriched, fraction 2 (Fr‐2) was a mixture of lymphocytes and myelomonocytic cells, and fraction 3 (Fr‐3) was enriched for myelomonocytic cells. The extent of T cell depletion was determined by limiting dilution analysis of the growth of T cells. The cells in each group were stimulated with phytohemagglutinin and cultured in the presence of interleukin‐2. These conditions allowed clonogenic growth of one of three T cells purified from peripheral blood. After a 3‐week culture period, replicate wells were scored for growth and precursor frequency was determined. The frequency of T cells in BMBC was 1/22 (n = 4), 1/16 in FR‐1 (n = 4), and 1/246 in Fr‐2 (n = 2), and in Fr‐3 it ranged from 1/3,000 to 1/10,000 (n = 4). For comparison, depletion of T cells from bone marrow by cytofluorographic sorting with OKT‐11 and twice E‐rosetting yielded 98.1% and 97.4% removal of T cells, respectively. Thus, the clonogenic assay assured that more than 99.3% of the original T cells were depleted by elutriation; however, hematopoietic progenitor assay (CFU‐GM, CFU‐GEMM, and BFU‐E) showed no enrichment in any particular fraction, implying that the progenitors measured in this assay are of diverse sizes. Elutriation represents a useful method for depletion of T cells from human bone marrow. Limiting dilution assay of T cell growth is a sensitive measure to monitor T cell depletion.
Long‐term follow‐up of prosthetic joint replacement in hemophilia
Authors: Rana Nasim A. , Shapiro Gary R. , Green David
Published: February 2007

We evaluated the outcome of seven severe hemophilic patients who underwent four total hip and four total knee arthroplasties since 1976. These patients have been followed at regular intervals over a period of 2.5–9.5 years (mean 5.8). Of the four total hip replacements, one had to be removed because of loosening and secondary infection 3 years after the initial surgery but was salvaged by pseudoarthrosis; the other three are pain‐free and radiologically stable and have an excellent range of motion 2.5, 5, and 7 years postoperatively. Of the four total knee replacements, one had to be removed because of infection but was successfully salvaged by arthrodesis; one patient has loose components, but the prosthesis is still functional; and the final patient with bilateral knee prostheses is pain‐free with limited but functional range of motion. Clotting‐factor replacement therapy was effective in controlling intraoperative bleeding, even in a patient with an inhibitor, and only one procedure was complicated by hematoma formation. We conclude that prosthetic joint replacement may be safely performed in hemophilic patients but should be reserved for those who have limited function because of severe pain, joint destruction, and deformity. Total hip arthroplasty is as successful in these patients as in nonhemophiliacs. Total knee arthroplasty provides relief of pain, reduces the frequency of hemarthroses, and corrects most of the deformity, but it is usually associated with a limited range of motion.
Management of treatment failures in thrombotic thrombocytopenic purpura
Authors: Liu Edison T. , Linker Charles A. , Shuman Marc A.
Published: February 2007

The prognosis and optimal management of patients with thrombotic thrombocytopenic purpura (TTP) who fail initial therapy with plasmapheresis or splenectomy are unclear. We report our experience with eight patients with TTP who did not respond to initial therapy. Seven patients achieved complete remission when alternate therapy was started soon after the recognition of initial treatment failure. One patient who received no alternative therapy died of progressive TTP. Our cases combined with those in the literature indicate a 74% salvage rate for patients who fail initial treatment for TTP. The combination of splenectomy, dextran, and steroids appears to be an effective treatment for patients with TTP who fail to respond adequately to plasmapheresis.
Isolated anterior chamber relapse in acute monoblastic leukemia
Authors: Hertler Andrew A. , Rosenwasser George O. , Gluck W. Larry
Published: February 2007

A case of acute monoblastic leukemia relapsing in the anterior chamber of the eye is described. Despite rigorous evaluation, no systemic or central nervous system involvement was detected. All previously reported cases of anterior chamber infiltrates in AML have had coexistent systemic or central nervous system disease.
Effects of a 4‐week freshwater fish (Trout) diet on platelet aggregation, platelet fatty acids, serum lipids, and coagulation factors
Authors: Atkinson P. M. , Wheeler M. C. , Mendelsohn D. , Pienaar N. , Chetty N.
Published: February 2007

Eight healthy subjects consumed a diet in which all animal products were replaced by 750 g/day of freshwater trout. Platelet eicosapentaenoic acid (EPA) as a percentage of total platelet fatty acids rose from a prediet level of 0.2±0.4% to 3.4±1.6% after 4 weeks on the diet. Platelet arachidonic acid remained unchanged. Platelets became more hyperaggregable to collagen (p<0.025) but became hypoaggregable to arachidonic acid (p< 0.05). The Ivy bleeding time became prolonged rising from a mean of 148 seconds before the diet to 168 seconds at 2 weeks and 202 seconds at 4 weeks. Serum lipids, coagulation profiles, and blood pressure remained unchanged. The changes induced by this diet were much less marked than changes induced by marine fish diets and diets supplemented by marine fish oil extracts, despite the fact that an equivalent amount of EPA was consumed and incorporated into platelets. These findings suggest that other substances, in addition to n‐3 unsaturated fatty acids, may be responsible for the antithrombotic properties of marine fish.
Clinical efficacy of desmopressin acetate for hemostatic control in patients with primary platelet disorders undergoing surgery
Authors: Kentro T. B. , Lottenberg R. , Kitchens C. S.
Published: February 2007

Desmopressin acetate (DDAVP) is efficacious in patients with von Willebrand's disease. It additionally appears to have value in patients with uremic or aspirininduced platelet dysfunction. We report here three patients with primary platelet defects who had previously experienced grossly inadequate hemostasis to whom we administered DDAVP. Each successfully underwent surgical procedures with DDAVP as the only hemostatic agent. Although the mechanism of these salutary effects is unclear, DDAVP may exert an influence directly on the endothelium independent of correcting abnormalities of the factor VIII: von Willebrand complex associated with von Willebrand's disease.
Platelet dysfunction associated with wilms tumor and hyaluronic acid
Authors: Bracey Arthur W. , Wu Alan H. B. , Aceves Javier , Chow Thomas , Carlile Shirley , Hoots W. Keith
Published: February 2007

Acquired von Willebrand disease (AVWD) has been described in two cases of nephroblastoma. We studied a patient with nephroblastoma who presented with a coagulopathy suggestive of AVWD. The subject had undetectable levels of F. VIIIR: Ag, diminished F. VIIIR: WF (16.3%), F. VIII: C activity (37%), and lack of platelet aggregation to ADP, epinephrine, collagen, and arachidonic acid. These results were associated with abnormally high serum levels (850 mg/dl) of hyaluronic acid (HA), which made the patient's serum hyperviscous. Examination of the neoplasm revealed HA in the tumor matrix. All abnormalities of coagulation resolved after chemotherapy and extirpation of the neoplasm, which produced normal serum HA levels.

To study the effects of HA on platelet function, we added HA to normal platelet‐poor plasma (NPP), which rendered F. VIIIR: Ag undetectable; treatment of HA with hyaluronidase eliminated F. VIIIR: Ag assay interference caused by HA. F. VIII: C activity decreased in vitro when HA was mixed with normal platelet‐poor plasma (NPP). HA reduced the initial slope of normal platelet aggregation. Partial correction of platelet aggregation occurred after hyaluronidase treatment of HA‐spiked PRP. Experiments in rabbits exposed to HA (serum level 400 mg/dl) demonstrated abnormalities similar to those noted in the patient. Shear rate studies of whole blood containing HA (500 mg/dl) yielded high shear stress, 27‐136 dynes/cm2 over shear rates of 10‐216 sec‐1. We conclude that the coagulopathy demonstrated in this case is secondary to hyperviscosity produced by elevated levels of HA, which interferes with the assay for F. VIIIR: Ag. Thus the acquired coagulopathy associated with other cases of nephroblastoma may present as spurious von Willebrand disease.
A variant of type II von willebrand disease with an abnormal triplet structure and discordant effects of protease inhibitors on plasma and platelet von willebrand factor structure
Authors: Gralnick Harvey R. , Williams Sybil B. , McCkeown Laurie P. , Maisonneuve Pascal , Jenneau Christine , Sultan Yvette
Published: February 2007

We have characterized the plasma and platelet von Willebrand factor (vWf) multimeric structure of a patient with von Willebrand disease (vWd) as having a long bleeding time, no aggregation of her platelet‐rich plasma (PRP) to ristocetin, and very low plasma and platelet von Willebrand antigen (vWf Ag) and vWf activity. The abnormalities of the plasma and platelet vWf have not been previously described. In particular, the patient's plasma and platelet vWf lacked the intermediate and largest vWf multimers and the slowest migrating minor band (band 1) of the triplet was markedly diminished compared to the major band (band 2) and the fastest migrating band of the triplet (band 3). A similar multimeric structure was seen in the platelet vWf. Collection of the patient's blood in protease inhibitors prior to the analysis of the platelet and plasma vWf structure revealed that the plasma vWf multimeric structure did not change, while the patient's platelet vWf showed a marked change with the appearance of the intermediate and large multimers and almost total disappearance of the abnormal multimeric structure. Direct comparison of this patient's plasma with previously reported cases of type IIA, IIC, and IID revealed marked differences in their multimeric organization compared to our patient. Employing the presently accepted convention, we have designated this variant type of vWd type IIG.
An acquired inhibitor to factor VIIIC in a non‐hemophiliac: Twenty years of observation and characterization
Authors: Coots Macie C. , Glueck Helen I.
Published: February 2007

A non‐hemophilic patient with an acquired inhibitor to factor VIIIC was initially diagnosed in this laboratory 20 years ago at age 63. Following its initial appearance in 1963, the inhibitor was detectable on two other occasions. We believe that this is the longest duration such an inhibitor has persisted. No sample remained from his initial admission; however, samples were available from the last 8 years of his life for retrospective study. Preparative isofocusing, affinity chromatography, and immunoglobulin subtyping were used to determine the similarities and/or differences in the inhibitor over these 8 years.

The following similarities and differences were observed in both the 1975 and 1983 plasmas. Isofocusing showed that both plasmas contained peaks of inhibitory activity with pIs of 7.25, 8.26, and 8.88; the 1975 sample in addition contained two peaks with pIs of 7.77 and 9.45, whereas two other peaks with pIs of 7.64 and 7.85 were found in the 1983 sample.

For the final characterization, each isofocused inhibitory peak was eluted from Protein A Sepharose and incubated with antisera to determine the immunoglobulin subtype. Each peak consisted of mixtures of IgG1 and IgG4 with both kappa and lambda light chains.

It was concluded that the inhibitor was polyclonal, based on the presence of inhibitory peaks with different pIs and immunoglobulin subtypes. These findings support the conclusion that the development of and changes in the inhibitor was a dynamic process with some inhibitors (antibodies) persisting, while at the same time others with different characteristics were being formed.
Isolated leukemia cutis—A case report
Authors: Haubenstock A. , Zalusky R. , Ghali V. S. , Mernick M. H. , Malamud S. C. , Stein J. J.
Published: February 2007

A 67‐year‐old woman with acute myelomonocytic leukemia had a clinical course characterized by the initial appearance of leukemia cutis without bone marrow involvement. When marrow involvement subsequently occurred, induction chemotherapy cleared all manifestations of the illness. Shortly thereafter, while blood and bone marrow remained in remission, the skin lesions reappeared. The introduction of 6‐thioguanine, as part of the maintenance treatment protocol, resulted in the rapid and permanent disappearence of the leukemic skin infiltrates.
Inhibitory effects of TTP sera on binding of anti‐platelet glycoprotein IIb‐IIIa monoclonal antibodies to human vascular endothelial cells
Authors: Nakajima Tokuo , Koyama Tetsuji , Kakishita Eizo , Nagai Kiyoyasu
Published: February 2007

The binding of anti‐human platelet glycoprotein (GP) IIbIIIa monoclonal antibodies to human umbilical vein endothelial cells (HUVE) was studied. Scatchard analysis using 125I‐anti‐platelet GPIIb‐IIIa monoclonal antibody showed that the maximum binding capacity (B max) was 8 × 104/cell and Kd was 40.2 nM. The binding rate of 125I‐anti‐platelet GPIIbIIIa monoclonal antibodies to HUVE treated with TTP sera was 11.6 ± 2.8%, compared with the 24.0 ± 7.5% observed for HUVE treated with normal sera. These findings showed that there are GPIIb‐IIIa on HUVE and that TTP sera may contain anti‐platelet GPIIbIIIa antibodies.
Acute non‐lymphocytic leukemia (ANLL) following treatment with dacarbazine for malignant melanoma
Authors: Carey Robert W. , Kunz Victoria S.
Published: February 2007

ANLL followed a brief period of aplastic anemia in a man treated intensively 4 years and 3 months previously with dacarbazine as “adjuvant” therapy for malignant melanoma. This is the first reported instance in which the latency between drug exposure and onset of leukemia strongly implicates dacarbazine as a leukemogenic agent.
Pocked erythrocyte counts in patients with hereditary spherocytosis before and after splenectomy
Authors: Buchanan George R. , Holtkamp Christine A.
Published: February 2007

The pocked (pitted or vacuolated) erythrocyte count has become increasingly utilized as a simple inexpensive test of splenic reticuloendothelial function. Values are less than 2.0% in normal subjects and 20 to 70% following splenectomy. Because scant and conflicting data are available about pocked erythrocyte measurements in hemolytic anemias other than the hemoglobinopathies, we performed pocked erythrocyte counts in 27 patients with hereditary spherocytosis. Prior to splenectomy patients often had elevated values (mean 4.9%). This unexpected observation suggests that hemolytic anemia may result in congestion of the red pulp and/or induce mild splenic reticuloendothelial blockade. As expected, but contrary to a previous report, pocked erythrocyte values following splenectomy were markedly increased (mean 54.9%).
Persistent remission of adult chronic autoimmune thrombocytopenic purpura after treatment with high‐dose intravenous immunoglobulin
Authors: Bierling Philippe , Divine Marine , Farcet Jean‐Pierre , Wallet Patrick , Duedari Najib
Published: February 2007

Transient efficacy of high‐dose intravenous immunoglobulin infusions (HDI) is widely demonstrated in autoimmune thrombocytopenic purpura (AITP). A trial involving repeated injections of HDI was conducted in two adult patients with chronic AITP in order to evaluate their long‐term efficacy in refractory forms and their ability to obviate splenectomy. Both patients received 2 g/kg body weight of polyvalent intact intravenous immunoglobulin followed by seven and eight boosters (0.8 to 1.2 g/kg body weight) when the platelet count decreased. It was found that the injections could be spaced progressively. The platelet count remained normal 200 and 800 days after the end of the treatment. The demonstration of the possible long‐term efficacy of repeated injections of intravenous immunoglobulin encourages us to recommend this safe therapy for patients with chronic AITP.
Peripheral blood remission of hairy cell leukemia after transfusion hepatitis
Authors: Keefer Michael J. , Weber Maril J. , Bottomley Sylvia S. , Solanki Dilip L. , Hosty Thomas A.
Published: February 2007

Hairy cell leukemia is a chronic lymphoproliferative disorder characterized clinically by splenomegaly and cytopenias. Spontaneous remissions are rare and splenectomy is often performed when the blood counts worsen and cause symptoms. Three of our patients with hairy cell leukemia developed recurrent pancytopenia and transfusiondependent anemia after splenectomy. Each subsequently acquired transfusion hepatitis and in two patients marked hematologic improvement was noted within 2 months. Complete peripheral blood remission occurred within 17 months in all patients although bone marrow infiltration with hairy cells persisted. One patient remains in remission for 12 years; the other two succumbed to infectious illnesses but with normal blood counts. The mechanism by which hepatitis virus induces hematologic recovery in patients with hairy cell leukemia is unknown but may involve augmentation of the interferon system.
Hairy leukemic cells which hyperexpress Ii do not demonstrate Ii genome alterations by restriction endonuclease analysis
Authors: Owerbach David I. , Elliott William L. , Humphreys Robert E.
Published: February 2007

The finding of increased expression and apparently altered processing of Ii in hairy leukemic cells led us to test for Ii genomic alteration by Southern‐type Ii cDNA hybridization to leukemic spleen DNA cleaved with a series of restriction endonucleases. Some insertions, deletions, or point mutations, potentially detectable by this technique, might correlate to alteration in expression and function of Ij (and indirectly, class II antigens). No changes in genomic structure of Ii were detected in DNA isolated from spleens of five patients with hairy cell leukemia, compared with DNA preparations from peripheral blood cells of nineteen healthy blood donors. These experiments were consistent with the view that gross structural alteration of the Ii genome had not occurred in hairy leukemic cells.
Thymic carcinoma and aplastic anemia: Report of a previously undocumented association
Authors: Vicky Thomas C. , Carlos Manivel J.
Published: February 2007

A case of thymic carcinoma documented after a 6‐year history of aplastic anemia is reported. The anemia responded initially to steroids and antithymocyte globulin. The carcinoma may have arisen in a previous undetected thymoma; alternatively, an underlying abnormality, presumably immunologic, played a role in the development of the anemia and the thymic carcinoma.
Thrombotic thrombocytopenic purpura in a human immunodeficiency virus (HIV)‐seropositive homosexual man
Authors: Jokela Janet , Flynn Thomas , Henry Keith
Published: February 2007

A case of thrombotic thrombocytopenic purpura (TTP) in a human immunodeficiency virus (HIV)‐seropositive homosexual man is reported. The patient improved after corticosteroid and plasma exchange therapy was instituted. The case demonstrated most of the classic features of TTP, including histologic evidence of fibrin thrombi in small blood vessels. Atypical features included reduced number of megakaryocytes in the bone marrow and only partial resolution of thrombocytopenia after therapy was begun. An autoimmune thrombocytopenia has been well‐characterized in HIV ‐antibody‐seropositive homosexual men. Physicians caring for HIV‐seropositive persons should also be aware of a possible association with TTP.
The greekaγβ+‐hpfh observed in a large black family
Authors: Huang H. J. , Stoming T. A. , Harris H. F. , Kutlar F. , Huisman T. H. J.
Published: February 2007

Several members of a Black family with a heterozygosity for an AγGβ+‐HPFH, shown in 1969 to have relatively low levels of Hb F and a low glycine to alanine ratio in the γ chain of this Hb F, were reinvestigated. Thirteen of 30 available family members in two generations had the heterozygous form of this condition, which was characterized by a decreased level of Hb A2, an average Hb FAD value of 13.3%, an equal distribution of Hb F over the red cells, and normal hematological values. The γ chain composition of isolated Hb F was determined by reversed phase high performance liquid chromatography for all 13 heterozygotes and showed an average Aγ value of 84.5 %. Hybridization with synthetic oligonucleotides, specific for normal and mutant sequences at positions 111–129 5′ to the Aγ globin gene, identified a G ± A base substitution at position 117, similar to that seen in subjects with the Greek Aγ‐HPFH. Our data support conclusions by others [15,16,30] that this replacement is causative of the increased Aγ chain synthesis in this condition. Haplotype analysis supported the suggestion that the G ± A substitution occurred as an independent event in this Black family.
Application of DNA polymorphisms for prenatal diagnosis of β thalassemia in chinese
Authors: Chan Vivian , Chan T. K. , Ghosh A. , Wong L. C. , Ma H. K. , Kan Y. W. , Todd D.
Published: February 2007

Forty‐seven Chinese suffering from β thalassemia major and their parents were studied to establish linkage of the βthal and βA genes with 11 restriction site polymorphisms. There is marked linkage disequilibrium at the BamH I site 3′ to the β globin gene, such that, in 31% of pregnancies, absence of the site in the fetus can exclude β thalassemia major. Using four restriction sites (Hinc II β, Ava II β, Hind III β, and BamH I β), prenatal diagnosis is feasible in all families. In 46% of all cases, a definitive diagnosis can be made, and in the remaining cases, a 50% chance of exclusion is possible. Fetal blood globin chain analysis would be required for the failures. Our experience in nine successive β thalassemia prenatal diagnosis is also reported.
A possible mechanism of increased sodium influx in red cells with abnormal membrane lipid levels induced by phospholipase A2
Authors: Hashimoto Masashi , Yawata Yoshihito
Published: February 2007

Membrane transport—sodium (Na+) influx and calcium (Ca2+) uptake—was examined in human mature red cells treated with phospholipase A2 (PLase A2) from snake venom. PLase A2‐induced conversion of phosphatidyl choline (PC) to lysophosphatidyl choline (L‐PC) was associated with a marked increase in Na+ influx and Ca2+ uptake. After L‐PC was removed from the cell membrane of the PLase A2‐treated red cells in the presence of albumin, an additional increase in Ca2+ transport was observed. These results indicate that membrane lipid abnormalities, such as increased L‐PC and/or a loss of total lipids, appear to induce increased membrane transport.
Natural variation in passive sodium permeability in human erythrocytes
Authors: Lee Jong Y. , Prineas Ronald J. , Hallaway Philip E. , Eaton John W.
Published: February 2007

The rate of influx of 22Na+ into human erythrocytes (RBC) varies greatly depending upon the donor. A high rate of influx may be related to a congenital predisposition to essential hypertension. In Northern Europeans, we find a threefold difference in the rate of 22Na+ influx between those with the least (LP) and most highly permeable (HP) RBC (from <0.15 to >0.60 mmol Na+/liter RBC/hr). In order to further define determinants of these apparently hereditary differences in passive membrane Na+ transport, we identified two groups of normal laboratory and hospital personnel differing markedly (> twofold) in RBC 22Na+ influx rate. We find that the loop diuretics furosemide and bumetanide decrease by about 50% the influx of 22Na+ into HP RBC, but have a lesser influence on LP RBC. Impermeant polyanions such as citrate and pyrophosphate also specifically diminish 22Na+ influx into HP, but not LP, RBC. Therefore, the exaggerated 22Na+ influx into HP RBC probably occurs through a discrete pathway (perhaps via “Na/K/Cl cotransport”), which appears to be almost absent in LP RBC. The differences between HP and LP RBC most likely do not involve polymorphisms of RBC anion transport per se. The rate of RBC anion (35SO42–) transport is the same in HP and LP RBC and is equally inhibited by furosemide and (to a lesser extent) bumetanide. Furthermore, the potent inhibitor of RBC anion transport, DIDS (diisothiocyanostilbene disulfonate) does not affect RBC Na+ permeability in either group. Nonetheless, the preferential reduction of Na+ permeation of HP RBC by loop diuretics may be of help in experimentally distinguishing HP from LP phenotypes. This information may be crucial in unraveling the structural basis of intrinsic differences in cell membrane Na+ permeability and their possible relationship to essential hypertension.