bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombocytopenic purpura in a carrier of human T‐cell leukemia virus type I
Authors: Matsuoka Tomoko , Tamura Hiroshi , Fujishita Masatoshi , Kubonishi Ichiro , Taguchi Hirokuni , Miyoshi Isao
Published: February 2007

Thrombocytopenic purpura developed in a 64‐year‐old woman seropositive for human T‐cell leukemia virus type I (HTLV‐I). She had no underlying disorders and HTLV‐I is suggested as a possible cause of her thrombocytopenia.
Clinical studies with low‐molecular‐weight heparin(oid)s: An interim analysis
Authors: Gate Hugo Ten , Henny C. Pieter , Cate Jan W. Ten , Büller Harry R.
Published: February 2007

In this review an interim analysis was made of all clinical studies performed with low‐molecular‐weight heparin(oid)s (LMWH) up to January 1987. Thus far, many experimental studies on LMWH show these substances to have an increased benefit/risk ratio concerning efficacy and bleeding as compared to standard heparin. In man, this increased ratio was verified in some small open studies. However, until the present day, controversy still exists. Some of the difficulties In assessing the results of different investigations include the existence of various kinds of LMWH and the lack of a consensus as to the unitage in which they are expressed. Furthermore, no international agreement exists as to the test measuring dosage/effect and its standard. In the following review all published clinical studies were analyzed for patient groups. Important issues concerning controversy with regard to efficacy, bleeding risk, diagnosis, and testing are discussed. In general, it may be concluded that LMWH have an antithrombotic potential comparable to that of heparin, and that the benefit/risk ratio I.e., decreased bleeding potential when compared to standard heparin, as found in animal experiments, has not been clearly demonstrated in man.
Unbalanced translocation (1;7) in childhood myelodysplasia
Authors: Horsman D. E. , Massing B. G. , Chan K. W. , Kalousek D. K.
Published: February 2007

We have identified an unusual pediatric patient among twelve patients with myelodysplasia and an unbalanced translocation involving chromosomes 1 and 7: −7, + der(1)t(1;7)(p11; p11). This 16‐year‐old male patient developed myelodysplasia and evolving acute leukemia, which were preceded by a 7‐year history of marrow hypoplasia. The remaining patients were adults with clinical and hematologic findings similar to other reported cases with this chromosomal abnormality. The late appearance of this unbalanced clonal abnormality in this patient with marrow hypoplasia documents the importance of close cytogenetic follow‐up of all patients with suspected bone marrow injury.
Hemoglobin pasadena: Identification of the gene mutant by DNA analysis using synthetic DNA probes
Authors: Rahbar Samuel , Rosen Robert , Nozari Guity , Lee Terry D. , Asmerom Yayesh , Wallace R. Bruce
Published: February 2007

Hemoglobin Pasadena [β75(E19)Leu→Arg] was found in a boy who had an acute episode of anemia and rapid splenic enlargement. His father was the only other member of a large family with this hemoglobinopathy. We have used gene mapping techniques for direct identification of the β‐globin gene mutation. To correlate the DNA findings with the structural identification of this variant, we have also performed globin chain separation and analysis of the tryptic peptides using high performance liquid chromatography and secondary ion mass spectral analysis.
Daunorubicin in patients with relapsed and refractory acute nonlymphoblastic leukemia previously treated with anthracycline
Authors: Velu T. , Debusscher L. , Stryckmans P.
Published: February 2007

While the efficacy of daunorubicin (DNR) in first induction of patients with acute nonlymphoblastic leukemia (ANLL) has been well documented, little data are available concerning the activity of DNR in patients with relapsed and refractory ANLL previously treated with anthracycline. We administered DNR (60 mg/m2/day for 3‐5 days) in 21 patients with relapsed (n=12) or refractory (n=9) ANLL previously treated with anthracycline. The general response rate was 48%, with a complete response (CR) rate of 38%. Five of 12 patients with relapsed ANLL and 3 of 9 patients with refractory ANLL achieved CR. Among these cases with CR in refractory ANLL, the evolution of one patient is particularly illustrative since he had received previously a large cumulative dose of anthracycline (540 mg/m2) and has been shown to be refractory to high‐dose cytosine arabinoside. This study suggests that previous administration of DNR or adriamycin does not Induce significant resistance to anthracycline: DNR appears to be almost as efficient in patients with relapsed and refractory ANLL previously treated with anthracycline as in first induction.
Congenital Pelger‐Huet anomaly in triplets
Authors: Ware Russell , Kurtzberg Joanne , Brazy Jane , Falletta John M.
Published: February 2007

Congenital Pelger‐Huet anomaly is an autosomal dominant disorder characterized by incomplete nuclear segmentation of granulocytes. The morphology of these mature but hyposegmented granulocytes may be confused with that of immature granulocytes (bands), thereby suggesting bacterial infection. We report the first known case of triplets with this condition, and emphasize the need to identify accurately this normal variant.
Chlorpromazine‐induced anticardiolipin antibodies and lupus anticoagulant: Absence of thrombosis
Authors: Canoso Rosa T. , De Oliveira Ricardo M.
Published: February 2007

Anticardiolipin antibodies were determined in 96 psychiatric patients treated chronically with chlorpromazine by an enzyme‐linked Immunosorbent assay using anti‐IgM and anti‐IgG (fab'2 fragment) as the second antibody. Fifty‐four of these patients had an IgM‐lupus anticoagulant, and the remaining 42 were followed as controls. Elevated IgM‐anticardiolipin antibodies (ACA) levels were detected in 31 patients with the lupus anticoagulant and in 5 controls (p<0.001). During a median followup of 5 years, single episodes of deep vein thrombosis or pulmonary embolism occurred in three patients; one had the lupus anticoagulant and the other two had low‐level ACA. Contrary to the reported experience in systemic lupus erythematosus and related autoimmune disorders, chlorpromazine‐induced lupus anticoagulant and anticardiolipin antibodies levels appear not to be associated with an increased incidence of thrombosis.
Type IIB von Willebrand's disease associated with a complex thrombocytopenic thrombocytopathy
Authors: López‐Fernández M. F. , López‐Berges C. , Martin‐Bernal J. A. , Sánchez R. , Villarón L. G. , Díez‐Jarilla J. , Batlle J.
Published: February 2007

A familial bleeding disorder characterized by an association of Type IIB von Willebrand's disease (vWD) with a complex thrombocytopenic thrombocytopathy is described in two patients from the same generation. Findings typical of type IIB vWD included enhanced ristocetin‐induced binding of patient von Willebrand factor (vWF) to platelets of patients and normal individuals in association with the absence of larger multimers from plasma. Abnormalities in platelet function included deficient platelet aggregation to ADP, collagen, epinephrine, and arachidonic acid; and defective release of 14C‐serotonin, vWF, and platelet factor 4 (PF4) in response to thrombin, collagen, or ADP. Platelet factor 4 and platelet vWF were decreased when measured per mg of total platelet protein. In addition, the binding of normal vWF to patient platelets stimulated with thrombin was decreased. Platelet size was increased with a very heterogeneous distribution width. Electron microscopic evaluation showed giant platelets with dense and alpha bodies present. The platelet count was borderline or slightly decreased in the resting state and declined to frankly thrombocytopenic levels at the time of acute bleeding episodes; this state was associated with the presence of platelet aggregates in blood smears.
Modulation of responsiveness of chronic myelogenous leukemia granulocyte‐macrophage colony‐forming cells to growth regulation following in vivo treatment with recombinant γ‐interferon
Authors: Pelus Louis M. , Vadhan‐Raj Saroj
Published: February 2007

A patient with Philadelphia chromosome (Ph) chronic myelogenous leukemia (CML), in chronic phase, was treated with recombinant γ‐interferon (rγ‐IFN) in a phase I clinical trial. Prior to treatment, analysis of in vitro agar culture parameters indicated hyporesponsiveness of granulocyte‐macrophage colony‐forming cells (CFU‐GM) to inhibition by prostaglandin E and acidic isoferritins and diminished expression of class II major histocompatibility complex (MHC) antigens (HLA‐DR). Treatment was associated with no change in bone marrow cellularity or in the percentage of Ph cells. However, in vitro cultures of bone marrow cells showed a return to normal levels of both expression of CFU‐GM class II antigen and of sensitivity to inhibition by prostaglandin E and acidic isoferritins which predicted and/or confirmed clinical response. Throughout the course of interferon therapy, white blood cell counts (WBC) and the percentage of bone marrow blast cells were maintained at normal levels. Onset of aggressive‐phase disease was associated with increased WBC, an increase in bone marrow blast cells, a secondary chromosomal abnormality, loss of CFU‐GM sensitivity to inhibition by putative negative growth regulators, and markedly diminished MHC class II antigen expression. Following a bone marrow transplant from a matched sibling, all hematologic parameters studied were found to be normal. These findings indicate that treatment with rγ‐IFN can modulate some of the abnormal growth characteristics of CFU‐GM observed in CML.
Transmission of human immunodeficiency virus to sexual partners of hemophiliacs
Authors: Smiley M. Lynn , White Gilbert C. , Becherer Paul , Macik Gail , Matthews Thomas J. , Weinhold Kent J. , McMillan Campbell , Bolognesi Dani
Published: February 2007

To examine the variables associated with heterosexual transmission of human immuno‐deficiency virus (HIV), we studied 32 couples in our hemophilia center who had steady sexual relationships for periods more than 1 year. Of the 32 sexual partners of the hemophiliacs, five (15.6%) were HIV seropositive. All five hemophiliacs with HIV transmission to their sexual partners had measurable immunologic deficiencies, as shown by their lower median T‐helper (CD‐4 +) lymphocyte count of 172 cells/mm3. The hemophiliacs without transmission had a slightly higher median CD‐4 + count of 297 cells/mm3 (P = 26). To determine if factors other than the degree of immunologic deficiency in the hemophiliac might contribute to HIV transmission, 18 of the 32 couples were studied more intensively by confidential, coded questionnaires. Regular condom use was reported by nine couples (50%). Two of nine women (22%) without condom usage acquired HIV. One of nine women (11%) using condoms was seropositive; she also reported eight needlestick injuries while assisting her spouse with clotting factor treatments. Intravenous drug abuse was reported in two of the five couples with HIV transmission. Thus, hemophiliacs are at risk for transmitting HIV parenterally as well as venereally. Despite various risk behaviors associated with HIV transmission, the prevalence of infection in our cohort of hemophiliacs' sexual partners is low and within the range (6.8–22%) reported by others. This study underscores the need for comprehensive education and counseling in what previously appeared to be a homogeneous clinic population at risk for transmitting HIV to others.
Thrombosis following desmopressin for uremic bleeding
Authors: Byrnes John J. , Larcada Alberto , Moake Joel L.
Published: February 2007

An elderly patient with evidence of atherosclerosis and uremic bleeding diathesis developed two foci of cerebral thrombosis immediately after an infusion of desmopressin (DDAVP). Because large molecular weight multimers of von Willebrand factor (vWF) have been demonstrated to cause platelet aggregation under conditions of elevated fluid shear stress as occurs in atherosclerotic vessels, we investigated his plasma vWF at the time of the event and compared it to baseline values obtained 2 weeks later. Unusually large vWF multimers induced by the DDAVP infusion were present and likely contributed to the thrombotic process. Consequently, we believe DDAVP should be given with greater caution to patients with atherosclerosis.
Cephalosporin‐induced immune cytopenia in the dog: Demonstration of erythrocyte‐, neutrophil‐, and platelet‐associated igg following treatment with cefazedone
Authors: Bloom John C. , Thiem Patricia A. , Sellers Teresa S. , Lewis Hugh B. , Deldar Ahmed
Published: February 2007

Cephalosporin treatment in man has been associated with a low incidence of hemolytic anemia, thrombocytopenia, and neutropenia; some cases have been shown to be immune‐mediated. This triad of blood dyscrasias was also demonstrated in our laboratory in a series of toxicity studies in dogs of two cephalosporin compounds, cefonicid and cefazedone; these studies provided evidence for drug‐associated immune hemolytic anemia, based on conventional laboratory tests. To further investigate possible immune mechanisms of the cephalosporin‐induced cytopenias, we measured erythrocyte‐associated, platelet‐associated (PAIgG), and serum antineutrophil IgG over the course of cephalosporin treatment, using highly sensitive 125I‐staphylococcal protein A (SPA) assays, as well as the direct antiglobulin test; we compared these findings with the hematologic changes. Intravenous treatment with high doses of cefazedone (540 mg/ kg/day, increased to a maximum of 840 mg/kg/day for 4 months or until hematologic effects were evident) resulted in a high incidence of anemia (7/14), thrombocytopenia (11/14), and neutropenia (7/14). Of the affected dogs examined, 6/7 with anemia, 9/9 with thrombocytopenia, and 7/7 with neutropenia showed increased levels of the respective cell‐associated antibody, compared with untreated controls. Unaffected dosed animals generally did not show these changes. In 3/3 dogs examined following remission of thrombocytopenia, PAIgG returned to levels comparable with controls; as one of these dogs suffered a relapse, increased PAIgG was again observed. Animals sacrificed during cytopenic episodes showed cytologic and histologic evidence of increased hemophagocytosis. We conclude that antibody‐mediated blood cell destruction contributes to all three cephalosporin‐induced cytopenias in the dog.
Isolated thrombocytopenia in patients infected with HIV: Treatment with intravenous gammaglobulin
Authors: Bussel James B. , Haimi Joseph S.
Published: February 2007

Isolated thrombocytopenia occurs frequently in patients infected with HIV. Studies of mechanisms of thrombocytopenia and clinical response to therapy suggest that the thrombocytopenia is often antibody mediated (ITP). The best approach to treatment of these patients is uncertain in that the routine modalities (steroids, splenectomy, vinca alkaloids) that are used to increase the platelet count in patients with classic ITP are known to be immunosuppressive. We report here the results of intravenous gammaglobulin (IVGG) treatment of 22 patients with HIV‐related acute and chronic ITP who had severe thrombocytopenia and bleeding symptoms. Only one patient had an opportunistic infection at the time of treatment. Eight patients were homosexual, eight had hemophilia, three were i.v. drug abusers, two children had congenital acquisition of HIV, and one was the wife of an HIV + i.v. drug abuser. The average pretreatment platelet count was 22,000/μl (hemophiliacs were treated at higher platelet counts than were the other patients), and the mean peak platelet count measured on days 5 to 8 was 182,000/μl. Nineteen of 22 patients had peak platelet counts >50,000/μl following IVGG and 17/22 had peak counts > 100,000/μl. After the initial infusions, all but three refractory patients could maintain adequate platelet counts with IVGG alone infused no more often than once every 2 weeks. The outcomes for the 22 patients after multiple maintenance IVGG infusions were remission, 5; stable without therapy, 1; maintenance, 13; and refractory, 3. The eight hemophiliacs with ITP responded better than did the eight homosexual ITP patients; their mean peak platelet count was 227,000/μl versus 142,000/μl in the homosexuals. In summary, patients with HIV‐related ITP without opportunistic infections responded well to IVGG, with peak platelet counts comparable to those of ITP patients not infected with HIV. IVGG may be a useful therapy of ITP in HIV + patients, since it appears to be less immunosuppressive than are conventional therapies, and none of the 22 HIV + patients developed an opportunistic infection while receiving IVGG alone.
An antibody to platelet membrane antigen associated with thrombotic events in essential thrombocythemia
Authors: Rock G. , Smiley R. K. , Tittley P. , Hashemi S. , McCombie N.
Published: February 2007

A 71‐year‐old man with essential thrombocythemia presented with acute onset of thrombosis in his fingers. The platelet count at presentation was 752 × 109/liter, and his PTT was within the normal range. Platelet aggregation was normal in response to ADP, decreased to epinephrine, and absent to collagen, with the patient receiving 1.2 g aspirin/day. Plasma vWF:Ag was 158 U/dl, VIII: C was 150 U/dl, and the vWF:Ag multirner pattern was normal. HLA antibodies were not detected in his serum, and the platelet‐associated IgG was normal at 3.9 fg/platelet. Incubation of normal, unactivated platelets with the patient's plasma did not result in agglutination of the platelets. However, a serum antibody reacting against a platelet antigen with an apparent molecular weight of 45,000 could be demonstrated by Western blotting. This antibody also reacted with endothelial cells. The reactive pattern was similar to that of commercially obtained actin; the serum antibody could be removed by preincubation with actin.

Platelet‐plasmapheresis was carried out daily for 10 days, after which the serum still reacted weakly with the platelet antigen. By day 20, the band could still be identified on the electroblot, but 2 weeks later no band could be seen. Similar assay of sera from six other patients with myeloproliferative disorders and comparable thrombocytosis but without thrombotic manifestations did not show any such reactions. The data suggest a correlation between the presence of an antibody possibly directed against platelet and/or endothelial cell actin and the vascular events in this patient with essential thrombocythemia.
Fetal lamb coagulation system during normal birth
Authors: Andrew M. , O'Brodovich H. , Mitchell L.
Published: February 2007

The contribution of the birth process to the unique coagulation system in the young was Investigated using the fetal lamb model. Specific components of the coagulation system were measured prior to and immediately following delivery of the lamb. The results show that the birth process itself does not contribute to the physiologically low levels of coagulation factors present in the newborn.
Intrasplenic lymphoma resembling multiple hematomas in a hemophiliac
Authors: Sweeney Joseph D. , Hassett James M.
Published: February 2007

A 42‐year‐old patient with hemophilia A developed acute left hypochondrial pain 8 days postnephrolithotomy. A colloidal scan indicated multiple hematomas, and conservative management was given. Postoperatively, recurrent discomfort necessitated splenectomy. Multiple space‐occupying lesions were found, and the histology was that of a large, noncleaved lymphoma. Contiguous spread outside of the capsule was evident, but abdominal nodes and liver appeared normal. Chemotherapy was administered, with evidence of tumor response, but refractoriness supervened, and the patient died 4 months after the diagnosis. Space‐occupying lesions in a hemophiliac are generally ascribed to hematomas. The exposure of this population to the human immunodeficiency virus (HIV) should raise the consideration of a non‐Hodgkin lymphoma in any situation where rapid clinical resolution of a hematoma is not occurring.
Failure of high‐dose I.V. Gammaglobulin in the treatment of spontaneously acquired factor VIII inhibitors
Authors: Heyman Meyer R. , Chakravarthy Anuradha , Edelman Bennett B. , Needleman Samuel W. , Schiffer Charles A.
Published: February 2007

Two patients with spontaneously acquired factor‐VIII‐CC inhibitors were treated with highdose i.v. gammaglobulin. Minimal inhibfiion of anti‐VIII‐CC activity was demonstrated in vitro in one patient when i.v. gammaglobulin was mixed directly with his plasma. In neither patient, however, was there any signficant reduction in titer of antifactor VIII‐C after i.v. gammaglobulin administration, nor was there any shortening of the aPTT or reduction in bleeding. The possible mechanisms of the previously reported salutary benefits of high‐dose i.v. gammaglobulin in patients with spontaneously acquired factor‐VIII inhibitors as well as the potential reasons for failure in our patients are discussed. Our cases demonstrated that high‐dose i.v. gammaglobulin is not uniformly successful in the treatment of patients with acquired factor‐VIII‐C inhibitors. The true frequency of clinically signficant responses will require further clinical trials.
Busulfan‐induced sideroblastic anemia
Authors: Fernandez Louis A. , Zayed Ekram
Published: February 2007

Patients in the stable phase of chronic myelogenous leukemia (CML) are usually treated with busulfan. The bone marrow of patients with CML may be exquisitely sensitive to busulfan, and occasionally such patients develop pancytopenia, secondary to hypoplasia or aplasia of the bone marrow, which is presumed to be due to busulfan‐induced marrow toxicity. We report a case of Philadelphia chromosome‐positive CML who developed pancytopenia while being treated with busulfan; however, the patient's bone marrow was not hypoplastic or aplastic but rather hyperplastic with sideroblastic changes. Busulfan is not known to cause sideroblastic changes, so this was considered to herald a transformation into acute leukemia. Busulfan was stopped, and only supportive treatment was given. To our surprise approximately 22 weeks after busulfan was stopped, the sideroblastic changes had disappeared and the bone marrow again showed features of CML. This case suggests that busulfan may cause sideroblastic anemia.
Physiologic formation of intracellular vesicles in mature erythrocytes
Authors: Sills Richard H. , Tamburlin Judith H. , Barrios Nilka J. , Yeagle Philip L. , Glomski Chester A.
Published: February 2007

The ability of mature erythrocytes to spontaneously form intracellular vesicles has been implied from clinical studies but has not been examined experimentally. An in vitro model was developed to demonstrate whether mature erythrocytes are capable of spontaneously forming intracellular vesicles. Normal human erythrocytes were incubated in vitro at 37°C for 144 hr in a synthetic medium. During the course of these incubations, approximately 4% of erythrocytes developed intracellular vesicles which were quantitated by using interference contrast microscopy. Electron microscopic studies confirmed the intracellular nature of these vesicles. Incubation of erythrocytes in autologous plasma produced similar results. The rate of vesicle acqulsition in vivo was measured by quantitating erythrocyte vesicles immediately prior to and following splenectomy. The rates of vesicle acquisition in vivo and in vitro were comparable. This in vitro model confirms the ability of mature erythrocytes to spontaneously form intracellular vesicles and strongly supports the concept that this is a physiologic process.
Some characteristics of human red blood cells separated according to their size: A comparison with density‐fractionated red blood cells
Authors: Vaysse Jenny , Vassy Roger , Eclache Virginie , Gattegno Liliane , Bladier Dominique , Pilardeau Paul
Published: February 2007

During their in vivo ageing, red blood cells (RBC) increase in density and become smaller. Age‐defined RBC subpopulations are usually collected by centrifugation. A fractionation according to RBC volume has been proposed as an improved alternative to such age separation. Because a few data reported in the literature indicate some discrepancies between the two methods, blood samples were separated either by centrifugation or by counterflow centrifugation, and some characteristics of the RBC thus fractionated were studied. The enzyme activities decrease either when the density rises or when the volume (MCV) decreases. However, the comparison of other RBC characteristics strongly suggests that these two procedures do not lead to the collection of the same RBC subpopulations: for instance, the hemoglobin content increases when the MCV rises, whereas it remains constant whatever the RBC density is. With radiolabelled cells, it is shown 1) that the most dense RBC are recovered in all the size‐separated RBC subpopulations, even though they tend to concentrate in the fractions with the largest MCV, and 2) that the smallest RBC are almost fairly distributed in all the RBC subpopulations, whatever their density, whereas the largest RBC are mainly, but not exclusively, present in the high‐density fractions. Thus, fractionation according to size does not match separation according to density. Taken together with results from in vivo experiments carried out in mice and with the fact that reticulocytes are present in all the size‐separated fractions, these data suggest that counterflow centrifugation may be a very questionable procedure to achieve a RBC fractionation according to age and therefore that RBC volume might not be a reliable criterion of RBC age.
Cell cycle distribution defect in PHA‐stimulated T lymphocytes of sickle cell disease patients
Authors: Abdallah J. M. , Kukuruga Mark , Nakeff Alexander , Prasad Ananda S.
Published: February 2007

T lymphocytes from normal human controls and sickie cell disease (SCD) patients were isolated from peripheral blood and cultured for 72 hours following addition of phytohem‐agglutinin. The ratio for the fraction of cells in DNA synthesis (S phase) over the fraction in G2 phase (S/G2) was significantly higher in SCD patients in comparison to the controls (mean ± SD) (4.01 ± 0.78 vs. 2.78 ± 0.76, P < 0.02). Following in vivo zinc supplementation to two subjects, the S/G2 ratio was normalized. We conclude that the distribution of T lymphocytes in cell cycle is altered in SCD patients and that this effect may be zinc‐de‐pendent.
Neonatal and maternal platelets: Activation at time of birth
Authors: Suarez Carlos R. , Gonzalez Jose , Menendez Cesar , Fareed Jawed , Fresco Raoul , Walenga Jeanine
Published: February 2007

Determination of the plasma concentrations of beta‐thromboglobulin (BTG), thromboxane B2(TxB2) and platelet factor 4 (PF4) were made at the time of birth in 18 newborns and their respective mothers. Both groups show significant elevation of all these molecular markers, suggesting marked platelet activation. The elevated TxB2levels in the newborn group, 25 ± 8 pg/ml, are compatible with a normally functioning and activated platelet prostaglandin pathway. Mode of delivery, vaginal or caesarean section, does not significantly influence the degree of activation in either group. Ultrastructural platelet examination did not reveal any morphologic differences between maternal and newborn platelets. There appears to be marked activation of the newborn and maternal platelet systems at the time of birth, and we postulate that this may explain in part the transient platelet dysfunction observed in newborns.
Effect of ferrous and ferric chelators on transferrin‐iron‐macrophage interactions
Authors: Baynes Roy D. , Friedman Brian M. , Bukofzer Gail T. , Bothwell Thomas H. , Macfarlane Bruce J. , Lamparelli Rosario D.
Published: February 2007

A study was done to evaluate the effect of ferrous and ferric chelators on the interaction between transferrin‐iron and cultured human blood monocytes. This interaction has been previously shown to involve a specific receptor and vesicle protonation. Transferrin‐iron uptake was significantly inhibited by the hydrophobic ferrous chelator 2,2′ bipyridine, and the inhibition was shown not to be a consequence of the mobilisation of intracellular iron by the chelator. Chase experiments and prolonged incubation studies suggested that the chelator prevented the iron released from transferrin from negotiating the unit membrane. The iron and transferrin then appeared to be returned independently to the incubation medium. In contrast, a hydrophilic ferrin chelator, desferrioxamine, had only a very modest effect on the interaction. These findings are compatible with the hypothesis that transferrin‐iron is reduced to the ferrous state during its uptake by the cultured human blood monocyte.
Monoclonal gammopathy and antibody activity against the acetylcholine receptor
Authors: Ahlberg Richard E. , Lefvert Ann Kari
Published: February 2007

A 50‐year‐old woman with muscular fatigue and monoclonal gammopathy of unknown significance was shown to have high levels of antibodies against the acetylcholine receptor of the skeletal muscle endplate. The specific antibody activity was exclusively associated with the monoclonal component. There were no objective signs of myasthenia gravis. This is the first reported case with antibody activity against the acetylcholine receptor found in a monoclonal immunoglobulin fraction.
Atypical haplotypes linked to the βs gene in Africa are likely to be the product of recombination
Authors: Srinivas Rao , Dunda Olga , Krishnamoorthy Rajagopal , Fabry Mary E. , Georges Alain , Labie Dominique , Nagel Ronald L.
Published: February 2007

We report here the haplotypes of 10 Mstll‐defined SS patients and a S/β0 thalassemia from the Central African Republic, exhibiting 7 different atypical haplotypes that are different from the typical Bantu haplotype that characterize over 93% of the βs bearing chromosomes in that region of Africa. Of the seven atypical haplotypes, six can be easily interpreted as the result of recombination around the “hot spot” 5′ of the β gene, between a typical Bantu haplotype and other haplotypes available in the normal population. Except for one case that requires further study, this result demonstrates that the main mutational event leading to sickle hemoglobin in Bantu‐speaking Africa was the mutation of the β gene in a Bantu haplotype background.
Interaction of heterozygous βo‐thalassemia with single functional α‐globin gene
Authors: Galanello Renzo , Paglietti Elisabetta , Melis Maria A. , Crobu Maria G. , Addis Maria , Moi Paolo , Cao Antonio
Published: February 2007

In this study, we analyzed the phenotypic manifestations resulting from the interaction of heterozygous βo‐thalassemia(βo‐39 nonsense mutation) with the functional loss of three α‐globin structural genes in six subjects, of whom four had the [‐αl–] α‐globin genotype and two the [–/αThα] α‐globin genotype. The β‐thalassemia defect was in all cases the nonsense mutation at codon 39. The nondeletion α‐thalassemia αth was the initiation codon mutation (AUG→GUG) of the α‐2 gene. In all these subjects hypochromia and microcytosis were more marked than in βα ‐thalassemia heterozygotes with a full complement of four α‐globin genes. All but one had moderate anemia. The α:β globin chain synthesis ratios were consistently decreased. No cases had Hb H on electrophoresis. Subjects with [–/αThα] α‐globin genotype had more severe thalassemia‐like manifestations than those with [–/‐α] α‐globin genotype.
Treatment of “poor risk” acute nonlymphocytic leukemia with continuously infused low‐dose cytosine arabinoside
Authors: Balaban Edward P. , Cox John V. , Schneider Nancy R. , Harth Cheryl A. , Haley Barbara B. , Sheehan Richard , Frenkel Eugene P.
Published: February 2007

There is currently little experience using a continuous intravenous infusion of low‐dose cytosine arabinoside (LDARA‐C) in the treatment of acute nonlymphocytic leukemia (ANLL). We report the results in 12 patients with ANLL described as either relapsed ANLL, ANLL with a preceding myelodysplastic phase, or ANLL in the elderly treated with 14 days of continuous intravenous LDARA‐C (20 mg/m2/day). Complete responses (CR) were seen in five patients (42%) and partial responses (PR) in three patients (25%). Treatment resulted in overall and clonal cytoreduction, which was evident by serial bone marrow exams and bone marrow cytogenetic analysis. The ability to obtain a CR correlated with the finding of a low initial marrow cellularity (P < .05). This study finds that continuous intravenous infusion of LDARA‐C for ANLL can achieve response rates comparable to standard induction programs in a subset of patients traditionally defined as having a poor prognosis.
Hematologic aspects of human immunodeficiency virus infection: Laboratory and clinical considerations
Authors: Perkocha Luke A. , Rodgers George M.
Published: February 2007

Hematologic abnormalities are common in patients with HIV infection. This review will focus on HIV‐associated cytopenias and coagulation abnormalities. Their occurrence, laboratory evaluation, and clinical significance and the mechanisms underlying their development are discussed. Therapeutic modalities are presented, with an emphasis on treatment strategies for HIV‐associated thrombocytopenia.
An unusual case of extramedullary blast crisis in chronic myelocytic leukaemia
Authors: Feng Chi‐Shun
Published: February 2007

A 27‐year‐old man with chronic myelocytic leukaemia sustained two episodes of extramedullary blast transformation. The first episode was a lymphoblastic transformation in his cervical lymph nodes, which was treated and in remission for 15 months when a second blastic transformation occurred in the meninges. All the while, the bone marrow was free from blastic crisis.
Polyclonal B‐cell lymphocytosis and hypergammaglobulinemia in patients with gaucher disease
Authors: Marti G. E. , Ryan E. T. , Papadopoulos N. M. , Filling‐Katz M. , Barton N. , Fleischer T. A. , Rick M. , Gralnick H. R.
Published: February 2007

Sera from 23 individuals with Gaucher disease (GD) were analyzed for hypergammaglobulinemia and oligoclonal and monoclonal gammopathies. Serum IgG level was elevated in 15/23 (65%) patients, and a diffuse hypergammaglobulinemia was present in 10/23 (43%) patients. An oligoclonal gammopathy was noted in six patients, and a monoclonal gammopathy in two. Lymphocyte subset analysis was also carried out in eight individuals with GD. Four of five individuals showed increased surface Ig‐positive lymphocytes, while 7/7 were positive for either increased CD19‐ and/or CD20‐positive lymphocytes. An eighth patient was found to have a B‐cell leukemia. Statistical analysis of k and λ histograms were suggestive of a monoclonal excess. However, restriction enzyme analysis of four individuals with GD and increased B cells failed to show any evidence of Ig gene rearrangements. Serum Ig abnormalities and perhaps B‐cell lymphocytosis appear to be common in the GD patient population and are not associated with circulating monoclonal lymphocytes.
Impaired echinocytic transformation of ankyrin‐ and spectrin‐deficient erythrocytes in mice
Authors: Reinhart Walter H. , Amy Sung L.‐P. , Sung K.‐L. , Bernstein Seldon E. , Chien Shu
Published: February 2007

The membrane skeleton of the red blood cell plays an important role in the determination of cell deformability and cell shape. Under various in vitro conditions, red blood cells undergo an echinocytic or stomatocytic shape transformation. The mechanism of this fundamental process is not well understood. We have studied the red cell shape transformation in normoblastic anemia mice (nb/nb) and spherocytic anemia mice (sph/sph), which are deficient in ankyrin and spectrin, respectively. We found that both ankyrin‐deficient cells (nb/nb) and spectrin‐deficient cells (sph/sph) have a reduced capacity to undergo echinocytic transformation with various echinocytogenic treatments, that is, incubation with sodium salicylate (40 and 120 mM), calcium loading (50 μM A23187 + 2.2 mM Ca2+), or metabolic depletion (24 hr at 37°C). These results suggest that the functional integrity of the membrane skeleton is essential for the maintenance and transformation of the red cell shape.
Familial type II protein C deficiency associated with warfarin‐induced skin necrosis and bilateral adrenal hemorrhage
Authors: Conlan Maureen G. , Bridges Alan , Williams Eliot , Marlar Richard
Published: February 2007

A family is described in which venous thromboembolic disease is associated with reduced plasma protein C activity and normal levels of protein C antigen. Immunoelectrophoretic analysis of protein C antigen gave an abnormal pattern in all affected members, suggesting that the disorder is related to the presence of a structurally and functionally abnormal form of protein C. The propositus developed simultaneous warfarin‐induced skin necrosis and bilateral adrenal hemorrhage. This is the first reported instance of warfarin‐induced skin necrosis associated with a dysfunctional protein C molecule and the first reported instance of simultaneous warfarin‐induced skin necrosis and bilateral adrenal hemorrhage.
Hemoglobin southampton (Casper): Characterization of the base mutation
Authors: Heintz Nicholas H. , Howard Phillip L.
Published: February 2007

Hemoglobin Casper is characterized by the substitution of cytidine for thymidine in condon 106 of the beta globin gene. This substitution results in the creation of a new restriction site for Msp I but not for the isoschizimer Hpa II. The restriction pattern following digestion with Msp I reveals a 9.9‐kb fragment not seen in normal individuals or following digestion of Casper DNA with Hpa II. This finding confirms the predicted base mutation and indicates that the cytidine in the newly acquired CpG site is methylated.
Comparative efficacy of nonheated and heat‐treated factor IX complex concentrate in treatment of hemophiliacs with inhibitors
Authors: Schwartz Richard S. , Ewing Nadia P. , Gorenc Toni J. , Spero Joel A.
Published: February 2007

To determine if heat‐treated factor IX complex concentrate is as effective as nonheated factor IX complex concentrate for treatment of subjects with hemophilia A and antifactor VIII antibodies (inhibitor patients), we have retrospectively reviewed consecutive home treatment records of ten inhibitor patients who had been receiving nonheat‐treated factor IX complex concentrate (NHT‐Konyne) and subsequently converted to heat‐treated factor complex concentrate (Konyne‐HT) when it was licensed in late 1984. Overall, 162 of 284 (57%) separate bleeding episodes treated with NHT‐Konyne and 53 of 80 (66.3%) separate bleeding episodes treated with Konyne‐HT required only one treatment course of ∼60‐75 U/kg. The distribution of bleeding sites and the absolute factor IX unitage required per treatment episode were similar for both preparations. These data suggest that the percentage of hemophilic inhibitor patients responding to factor IX complex concentrate remains at least 50%, as was reported several years ago in a controlled study, and that inhibitor bypass activity has not altered by heat treatment.
Biochemical assays of hemoglobin in normal human erythroid clones
Authors: Barr Ronald D. , Koekebakker Marijke
Published: February 2007

Quantitation of small amounts (2–3 μg) of hemoglobin (Hb) was achieved by each of three spectrophotometric techniques. An assay employing benzidine base consistently underestimated Hb at this level and gave a wide scatter of results at higher values. The cyanmethemoglobin method was at the limit of its sensitivity and suffers from the disadvantage of having high optical densities in the blank samples. By contrast, pyridine hemochromogen can be detected accurately with 200 ng of Hb (equivalent of 6,000 mature erythrocytes), and the regression line with this technique virtually passes through the origin. Furthermore, the extinction coefficient of pyridine hemochromogen in the Soret band is 13.5‐fold greater than that of cyanmethemoglobin. In normal human erythroid clones, generated in vitro from bone marrow cells, mean cell hemoglobin (MCH) values were determined after various intervals of culture. The MCH after 5, 7, 10, and 14 days were 11.8, 15.8, 26.6, and 34.4 pg, respectively, by the pyridine hemochromogen method. Reaction product was also identified in granulocyte‐macrophage clones, presumably reflecting the content of other heme proteins such as catalase and cytochromes. Account must be taken of this non‐Hb material in computing true MCH values for erythroid cells.
Sex practice correlates of human immunodeficiency virus transmission and acquired immunodeficiency syndrome incidence in heterosexual partners and offspring of U.S. hemophilic men
Authors: Lawrence Dale N. , Jason Janine M. , Holman Robert C. , Heine Peggy , Evatt Bruce L.
Published: February 2007

We assessed the risk of human immunodeficiency virus (HIV) transmission from heterosexual seropositive hemophilic men to their female sex partners through an HIV sero‐survey and questionnaire study conducted during 1984–1987. Five percent of 21 female partners of asymptomatic men and 11% of 35 partners of HIV‐symptomatic (acquired immunodeficiency syndrome [AIDS], AIDS‐related complex [ARC], peripheral generalized lymphadenopathy [PGL]) hemophilic men had been infected when first tested. One of 19 seronegative women tested about 1 year later reportedly seroconverted. Only 18% of a sample of the serosurvey women responding to sex practices questions said their partners used condoms “nearly always.” Over 60% engaged in oral/genital sex in addition to vaginal intercourse. Only 12% of still‐seronegative women followed the preventive strategy of consistent avoidance of oral/genital sex, together with consistent condom use by the male partner.

Further evidence for heterosexual transmission comes from the CDC national AIDS surveillance reports showing 25 women who acquired HIV infection through heterosexual contact with U.S. hemophilic men (September 6, 1988). Seven (28%) were diagnosed and reported in the first 6 months of 1988. Their ages range from 20 years to more than 70 years. The dates of infection for the women are unknown but must have been at least 5 years before AIDS diagnosis for at least one. Only approximately 30% of their male partners had already manifested any HIV‐assodaied illness.

Through May 18, 1988, six cases of AIDS have occurred in children whose infection was acquired through exposure of the mother to a hemophific partner. Four were diagnosed in latter 1987. The median age at diagnosis was 4.5 months. Four had died. None of their mothers is as yet diagnosed.
Apparent response of refractory post‐transfusion purpura to splenectomy
Authors: Cunningham C. Casey , Lind Stuart E.
Published: February 2007

Post transfusion purpura (PTP) is a rare disorder characterized by the abrupt onset of severe thrombocytopenia following transfusion. A patient with PTP and massive bleeding was refractory to corticosteroids, gamma globulin, and plasma exchange but developed an immediate and sustained rise in platelet count following splenectomy. Splenectomy may be a useful therapeutic modality in patients with refractory PTP.
Evaluation of factor VIII pharmacokinetics in hemophilia‐A subjects undergoing surgery and description of a nomogram for dosing calculations
Authors: Longo G. , Messori A. , Morfini M. , Baudo F. , Ciavarella N. , Cinotti S. , Filimberti E. , Giustarini G. , Molinari A. C. , Ferrini Pierluigi Rossi
Published: February 2007

The pharmacokinetics of factor VIII were studied in a series of 20 hemophilia‐A patients undergoing surgery. Regardless of the type of operation, elimination of factor VIII was shown to be increased only in ten cases (50%) during the post‐operative period. In this subgroup of patients, factor VIII half‐life, measured immediately after surgery, was considerably shorter (mean = 9.6 hr, n = 10) than that determined in the same individual during the late operative period (mean = 17.8 hr, n = 10). These findings indicate that identification of patients with increased postoperative consumption of factor VIII can be of value in reducing the risk of hemorrhage in these subjects and in exposing other subjects with no postoperative increase in factor VIII clearance to less of the deficient factor. Data from 20 subjects were analyzed to construct a nomogram allowing individualized prediction of factor VIII dosing requirements. The nomogram, which is based on the “single point after a single dose” method, uses a value of factor VIII concentration measured at 10 hr after preoperative loading dose to predict the regimen producing the desired average steady‐state concentration of factor VIII (30, 60, or 90 units/dl).
Spontaneous platelet aggregation in type IIB tampa von willebrand disease is inhibited by the 52/48‐kDa fragment of normal von willebrand factor, which contains the GPIb binding domain
Authors: Saba Hussain I. , Fujimura Yoshihiro , Saba Sabiha R. , Bruce Anita C. , Morelli Genevieve A. , Ruggeri Zaverio M. , Zimmerman Theodore S.
Published: February 2007

The association of Type IIB von Willebrand disease (vWD) with chronic persistent thrombocytopenia and spontaneous platelet aggregation has recently been recognized. It has been shown that IIB von Willebrand factor (vWF) can initiate platelet aggregation by binding to the platelet glycoprotein (GP) lb receptor and inducing exposure of the Gpllb/llla fibrinogen receptor. In this study we demonstrate the increased binding of Type IIB Tampa vWF with normal platelets when compared with nonthrombocytopenic Type IIB vWF. Studies further demonstrate that spontaneous platelet aggregation initiated by IIB Tampa vWF can be blocked by a 52/48‐kDa fragment of normal vWF, which contains the binding domain.
Adult‐onset cyclic bicytopenia: A case report and review of treatment of cyclic hematopoiesis
Authors: Tefferi Ayalew , Solberg Lawrence A. , Petitt Robert M. , Willis Larry G.
Published: February 2007

A unique case of adult‐onset synchronous cyclic neutropenia and thrombocytopenia occurring at six‐week intervals is presented. Periods of cytopenia were associated with fever, myalgias, gastrointestinal symptoms, and mild mucocutaneous bleeding. Alternate‐day steroid treatment failed to correct the periodic fluctuations in peripheral blood counts but ameliorated symptoms during cytopenia. The treatment of cyclic hematopoiesis is reviewed.
Factor VIII inhibitor in insulin‐dependent diabetes mellitus
Authors: Wajima Takeshi , Hall Gregory
Published: February 2007

Acquired factor VIII inhibitor was found in a 69‐year‐old white male with insulin‐dependent diabetes mellitus. He presented with left lower abdominal pain and hematoma after a fall. Preoperative hemostasis studies were normal except for prolonged aPTT. Prolonged aPTT was not corrected by 1:1 mixture with normal fresh plasma and incubation showed further prolongation with time. Factor VIII:c was 3.5%. The inhibitor titer was 7.5 Bethesda units. The possible mechanism causing antibody to factor VIII was postulated to be an autoimmune process and/or increased immunogenicity owing to glycosy‐lation of factor VIII coagulant protein.
Seventeen‐year survival in multiple myeloma
Authors: Suyehira Lisbeth A. , Lawrence H. Jeffrey
Published: February 2007

We report a case of multiple myeloma surviving 17 years since diagnosis and 13 years in continuous complete remission since a relapse 4 years after initial treatment. Despite the prolonged remission, multiple lytic bone lesions have not healed.