bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemoglobin dhonburi α2β2 126 (H4) Val → Gly: A new unstable β variant producing a β‐thalassemia intermedia phenotype in association with β°‐Thalassemia
Authors: Bardakdjian‐Michau J. , Delanoe‐Garin J. , Lacombe C. , Blouquit Y. , Riou J. , Galacteros F. , Fucharoen S. , Winichagoon P. , Wasi P. , Kister J.
Published: February 2007

While investigating the mechanism of a β‐thalassemia intermedia phenotype in a 34 year old Thai male, a new Hb variant β 126 Val → Gly named Hb Dhonburi was discovered. Genetic and structural studies revealed the existence of a β°‐thalassemia genotype in association with the β variant. The new variant is unstable but exhibits normal oxygen binding properties. Hb Dhonburi was also discovered in the mother of the propositus in association with Hb E.
Acquired von willebrand disease in multiple myeloma secondary to absorption of von willebrand factor by plasma cells
Authors: Richard C. , Cuadrado M. A. , Prieto M. , Batlle J. , Fernández M. Flópez , Salazar M. L. Rodriguez , Bello C. , Recio M. , Santoro T. , Casares M. T. Gomez , Zubizarreta A.
Published: February 2007

A case of acquired von Willebrand disease (AvWD) associated with an IgA lambda multiple myeloma is reported. No form of inhibitor could be detected. SDS‐agarose gel electrophoresis patterns of von Willebrand factor (vWF) both in plasma and platelet lysates were normal but a decrease in all‐sized multimers with a type IA pattern was seen. After 1‐deamino‐8‐D arginine vasopressin (DDAVP) infusion, vWF multimers larger than those seen in the resting state appeared in patient plasma, which were progressively cleared. Indirect immunofluorescence studies with a monoclonal antibody to vWF showed that vWF was selectively absorbed into myelomatous cells. This is the first case of AvWD associated with multiple myeloma resulting from the selective absorption of vWF into abnormal plasma cells.

This feature established a new pathophysiological mechanism of AvWD in multiple myeloma and probably in other lymphoproliferative diseases.
Proliferation and differentiation of erythroid progenitors in liquid culture: Analysis of progenitors derived from patients with polycythemia vera
Authors: Fibach Eitan , Rachmilewitz Eliezer A.
Published: February 2007

We have recently described a new two‐phase liquid culture that supports the development of human erythroid progenitors (Fibach et al., Blood 73:100, 1989). The procedure separates the erythroid burst‐forming units (BFUe) from the erythroid colony‐forming units (CFUe) stage and enables quantitation of the proliferation and differentiation of BFUe into CFUe. In the present study we have utilized this system to study erythroid progenitors in polycythemia vera (PV). The abnormality of the erythroid series in PV has been shown to be associated with an increased responsiveness of the progenitors to the hormone erythropoietin (Epo). A basic question in this clonal stem cell disorder is at what developmental stage this abnormality of the PV clone is phenotypically expressed. We have studied this question by comparing the development of Epo‐dependent and Epo‐independent CFUe from peripheral blood BFUe of the PV patient during the BFUe to CFUe transition in the liquid culture. The results indicated that both types of CFUe are generated and that in all cases tested the ratio of Epo‐independent progenitors at both the BFUe and CFUe stage was similar indicating no preferential development of Epoindependent CFUe. These results suggest that the abnormality of the PV erythroid progenitors is expressed only at the CFUe level. Moreover, since the liquid culture did not contain Epo, the results also support the conclusion that BFUe do not require Epo for proliferation or differentiation into CFUe.
Efficacy of the high molecular weight fraction of plasma for the maintenance of pregnancy associated with thrombotic thrombocytopenic purpura
Authors: Koyama Tetsuji , Suehiro Akira , Kakishita Eizo , Taira Shozo , Isojima Shinzo , Norioka Mihoko , Ito Kazuhiko
Published: February 2007

We have investigated the methods for the maintenance of a pregnancy in a patient with thrombotic thrombocytopenic purpura (TTP), said condition, since 1984, having been controlled by a plasma infusion every 3 to 4 weeks. In a preliminary trial it was confirmed that an infusion of the high molecular weight fraction (HMW‐F) of plasma, separated by an Evaflux® 2A fractionator, improved the patient's thrombocytopenia as the plasma infusion, and maintained its beneficial effect for about 2 weeks during early pregnancy. Though an occurrence of a toxemia‐like syndrome responded to repeated plasma infusion, the dose of plasma required to improve the thrombocytopenia gradually increased and reached 5,040 ml by the 20th week of pregnancy. Thus, instead of periodic infusions of whole plasma, periodic infusions of the HMW‐F of plasma were used. Under this regimen the platelet count remained above 10.0 × 104/μl during late pregnancy, and the total dose (2,600 ml) of HMW‐F of plasma that was administered until delivery at full term was less than the dosage of whole plasma that was used during early pregnancy. In this manner we were able to obtain a healthy baby by controlling the patient's TTP during pregnancy. This method of preventing thrombocytopenia appears to be safer with respect to volume loading during pregnancy in the TTP patient.
Disseminated intravascular coagulation and hemorrhage in hemophilia B following elective surgery
Authors: Conlan Maureen G. , Hoots W. Keith
Published: February 2007

Two patients with hemophilia B are described in whom disseminated intravascular coagulation (DIC) developed following infusion of repeated doses of Factor IX concentrate in the perioperative period. In both cases the surgery was elective, Factor IX survival studies had been done to assure proper dosing, and Factor IX levels were monitored daily. Neither patient had clinically significant liver disease. The DIC manifested itself as excessive blood loss from surgical drains without documented thrombosis and was accompanied by prolonged coagulation times, increased fibrin split products and decreased fibrinogen and platelets. In both patients the process was quickly reversed with administration of fresh frozen plasma, cryoprecipitate, and the addition of heparin to the Factor IX concentrate. These cases highlight the difficulty in managing patients with hemophilia B undergoing surgical procedures due to the potential thrombogenicity of the currently available concentrates, and the importance of differentiating the bleeding associated with DIC from underdosing with Factor IX. Furthermore, the potential complications associated with the presently available Factor IX concentrates stress the need for the development of purer, safer Factor IX concentrates.
Familial case of may‐hegglin anomaly associated with familial spastic paraplegia
Authors: Fujita Yukihisa , Fujii Tsuneo , Nishio Akira , Tuboi Kazuhiko , Tsuji Katuhiko , Nakamura Mituo
Published: February 2007

We report a family with May‐Hegglin anomaly associated with familial spastic paraplegia. The propositus was a 39 year old male. His peripheral blood showed a Döhle‐like inclusion bodies in WBC, giant platelets, and thrombocytopenia. He had been suffering from progressive gait disturbance of spastic paraplegia since 20 years old.

He was in a state of chronic renal failure and showed sensory hearing impairment. His two children showed similar hematological abnormalities and spastic gait. As far as we know, this is the first case of May‐Hegglin anomaly associated with familial spastic paraplegia in the literature.
Dry tap bone marrow aspiration: Clinical significance
Authors: Humphries John E.
Published: February 2007

Failure to obtain bone marrow on attempted marrow aspiration, “dry tap”, has commonly been ascribed to faulty technique. All reports of simultaneous marrow aspirations and biopsies performed at the University of Virginia between January 1, 1983, and July 1, 1989, were reviewed to determine the frequency of dry taps, the diagnoses and pathologic findings in these cases, and the associated laboratory findings. Among 2,235 simultaneous bone marrow aspirations and biopsies, 87 were dry taps (3.9%). Of these 87 dry taps, only six (6.9%) showed normal marrow biopsies, whereas the majority showed significant marrow pathology, usually associated with fibrosis, or hypercellularity, or both. These conditions most likely account for the inability to aspirate marrow. The most frequent diagnoses were metastatic carcinoma (17.2%), chronic myelogenous leukemia (14.9%), idiopathic myelofibrosis (13.8%), and hairy cell leukemia (10.3%). The presence of peripheral blood nucleated red blood cells, thrombocytopenia, and elevation of the serum lactate dehydrogenase were frequent findings in patients who experienced dry taps. Methods to obtain sufficient marrow for rapid diagnosis in these cases are discussed.
Recurrent disseminated intravascular coagulation and fulminant intra hepatic thrombosis in a patient with the anti‐phospholipid syndrome
Authors: Stinson J. , Tomkin G. , McDonald G. , Jackson F. , Harrison M. , Murray A. , Feighery C. , Jackson J.
Published: February 2007

We describe a patient with the lupus anti‐coagulant who had recurrent episodes, over a 2 year period, of a severe and disseminated intravascular coagulopathy. This patient also had positive serological assays for syphilis and anti‐cardiolipin antibodies. Associated with the coagulopathy were co‐expressed episodes of liver disease, ultimately terminating in fulminant liver failure. At autopsy the features were characteristic of the Budd‐Chiari syndrome. This is the first report to document how consumptive coagulopathy may present as a dominant feature of the anti‐phospholipid syndrome. It also clearly describes an immune mediated thrombotic mechanism as a cause of hepatic veno‐occlusive disorders. Furthermore, this case highlights the varied clinical spectrum of the anti‐phospholipid syndrome and suggests that a high index of suspicion is required to ensure its diagnosis.
Antithrombin III‐Amiens: A new family with an Arg47 → cys inherited variant of antithrombin iii with impaired heparin cofactor activity
Authors: Roussel B. , Dieval J. , Delobel J. , Fernandez‐Rachubinski F. , Eng B. , Rachubinski R. A. , Blajchman M. A.
Published: February 2007

A family with an antithrombin III variant (AT‐III‐Amiens) demonstrating abnormal heparin cofactor activity is described. Amplification and direct sequencing of genomic DNA by the polymerase chain reaction procedure permitted the identification of an Arg47 Cys mutation in exon 2 of the variant antithrombin III gene.
Clinical pharmacokinetics of a placenta‐derived factor XIII concentrate in type I and type II factor XIII deficiency
Authors: Rodeghiero Francesco , Tosetto Alberto , Bona Eros Di , Castaman Giancarlo
Published: February 2007

Limited data are available about the pharmacokinetics of placenta‐derived factor XIII (FXIII) concentrate in patients with FXIII deficiency. This concentrate contains only the active subunit A but not the carrier subunit B of the factor, and perplexities have been raised about its clinical use. Moreover, no data are available on its use in the rare patients completely lacking both subunit A and subunit B. Therefore, we evaluated the pharmacokinetics of a commercial placenta concentrate in three patients with FXIII deficiency: two lacking subunit A (type II) and one lacking both subunits (type I).

The elimination half‐life of the infused placenta subunit A in the three patients was very similar (280, 283, and 272 hr) and was also consistent with the previously reported data for plasma‐derived FXIII. No thrombin‐independent activity was observed in our concentrate batches. The recovery was significantly lower in the type I patient, in whom infusion of subunit A was not able to elicit a monthly increment of subunit B, as usually observed in type II patients. Monthly infusions of placenta concentrate (at higher dosage in type I patient) have been administered to our patients for two to three years and no evidence of inhibitor against factor XIII activity has been observed.

We conclude that placenta concentrates may be as effective as plasma derivatives in replacement therapy of factor XIII deficiency, even in patients who lack subunit B.
Humoral immune responses to gag and env proteins from human immunodeficiency virus type 1 in hemophiliac patients
Authors: Kinney Janet S. , Conway James H. , Hilgartner Margaret W. , Clayman Barbara , Mayur Kumudini , Yolken Robert H. , Viscidi Raphael P.
Published: February 2007

Solid‐phase enzyme immunoassays using recombinant gag and env proteins were developed to study humoral immune responses to HIV infection in a cohort of 105 hemophiliac patients. Thirteen patients with ARC or AIDS and 92 asymptomatic patients were studied. A cross‐sectional study showed a wide range of antibody responses to gag and env proteins; however, the differences between the ARC/AIDS and asymptomatic patients were statistically significant for both antigens (P < .0004). In a longitudinal study, antibody levels in sera from 11 asymptomatic patients with gag antibody log units ≦ 1.5 were compared to levels in sera from 10 ARC/AIDS patients and 8 asymptomatic patients with gag antibody >1.5. These patient groups were followed for comparable periods of time (67.1‐71.7 mo). The asymptomatic patients with low gag antibody and the ARC/AIDS patients showed a similar pattern of antibody response to gag protein overtime. In hemophiliac patients with HIV‐1 infection a low titer of antibody to gag protein is not invariably associated with clinical deterioration and is not a useful serologic marker of impending progression to AIDS.
Neutrophil alkaline phosphatase activity in the urinary neutrophils of a patient with chronic myelogenous leukemia
Authors: Janković Gradimir , Petrović Milan , Čolović Milica , Žilić Mirjana , Dotlić Rajko
Published: February 2007

We report here a patient with Philadelphia chromosome (Ph)‐positive chronic myelogenous leukemia (CML) in chronic phase in whom the alkaline phosphatase activity of neutrophils in the peripheral blood was low while at the same time the alkaline phosphatase content of neutrophils present in the urine was elevated. This observation provides independent clinical support for the recent experimental finding that an extrinsic factor (granulocyte colony‐stimulating factor) controls alkaline phosphatase expression in human neutrophils.
Antiplatelet antibodies in childhood idiopathic thrombocytopenic purpura
Authors: Özsoylu Şlinasi , Karabent Adnan , Irken Gülersu , Tuncer Murat
Published: February 2007

Antiplatelet antibodies were shown by the Handin and Stossel method in the sera of all 103 patients with acute ideopathic thrombocytopenic purpura (ITP) and in 100 cases following recovery from it. These antibodies were also shown in the sera of all 46 patients with chronic ITP and 32 cases after recovery. The decrease in level of antiplatelet antibodies was significant in all these children following recovery (P < 0.001 for acute ITP, P < 0.05 for chronic ITP). Antiplatelet antibodies could be determined in 67 acute and 21 chronic ITP cases in thrombocytopenic phase and following recovery, which showed very significant decreases in levels in each case in a later period. Antiplatelet antibody levels corresponding to the thrombocytopenic phase and recovery in acute and chronic ITP were significantly higher than normal and thrombocytopenic control values (P < 0.001 for each).
T‐lymphoid blast crisis in chronic myeloid leukemia
Authors: Advani S. H. , Malhotra H. , Kadam P. R. , Iyer R. S. , Nanjangud G. , Balsara B. , Saikia T. , Gopal R. , Nair C. N.
Published: February 2007

Chronic myeloid leukemia (CML) is considered to be a pleuripotential stem cell disorder with the capacity to differentiate into myeloid, erythroid, megakaryocytic, and lymphoid cell lines. Consequently, blast crisis (BC) involving each of the above lineages has been well described. Among lymphoblastic crises, differentiation frequently occurs along B‐cell lineage. We report four patients of CML who terminated in T‐cell extramedullary BC in lymph nodes after a variable duration of chronic phase. The T‐lineage was established by characteristic cytochemical staining and reactivity with a panel of anti‐T‐cell monoclonal antibodies. All four cases were Philadelphia (Ph) chromosome positive and demonstrated the Ph chromosome and associated anomalies (extra Ph, +19) in the lymph nodes. Our data adds to the growing evidence that CML is a disorder of the common stem cell from which T, B, and myeloid precursors originate.
Erythropoietin life span in rats with hypoplastic and hyperplastic bone marrows
Authors: Piroso Ettore , Erslev Allan J. , Flaharty Kristen K. , Caro Jaime
Published: February 2007

The metabolic fate of erythropoietin (EPO) remains unknown. Urinary excretion does not appear to play a major role and liver catabolism has been shown to occur only after terminal sugars on the hormone have been removed. However, it has been proposed that EPO is eliminated by consumption in the bone marrow. In order to examine the extent of such consumption we measured the half‐life of radioidinated recombinant EPO injected intravenously (IV) to rats with bone marrows suppressed by cyclophosphamide or hypertransfusion and marrows stimulated by phenylhydrazine or bleeding. The mean half‐life or erythropoietin in normal rats was 179 ± 16 min, with similar half‐lives found in the other rats regardléss of decreased or increased bone marrow activity. The results indicate that it is unlikely that erythroid activity determines EPO life span and catabolism.
Abnormal proteolytic degradation of von willebrand factor after desmopressin infusion in a new subtype of von willebrand disease (ID)
Authors: Lopez‐Fernandez M. F. , Gonzalez‐Boullosa R. , Blanco‐Lopez M. J. , Perez M. , Batlle J.
Published: February 2007

We describe two members of a single family, father and son, with mild factor XII deficiency associated to von Willebrand disease (vWD) with aberrant structure in whom distinct multimeric abnormalities and an abnormal proteolytic processing of von Willebrand factor (vWF) after desmopressin (DDAVP) administration were present. They had a mild bleeding history, low levels of vWF‐related activities, and a prolonged bleeding time. Low‐resolution agarose‐ gel electrophoresis showed a vWF with all size multimers in plasma and platelets. Higher‐resolution agarose gels demonstrated that the main band was present, but the relative proportion of the satellite bands was markedly reduced. The smallest oligomer was not increased. After the infusion of DDAVP to the father, a transient increase in the relative proportion of the satellite bands was seen, as described in normal individuals. No difference in the structure of vWF was observed when blood was collected with proteinase inhibitors. The analysis of native subunits of vWF and their proteolytic derived fragments, after DDAVP administration, showed a temporary augmentation of the 176 kDa fragment, as seen in normal subjects, as well as an increase of the 189 kDa fragment. This finding had not been reported previously either in normal individuals or in patients with vWD.
High‐dose dexamethasone for refractory or relapsing multiple myeloma
Authors: Friedenberg William R. , Kyle Robert A. , Knospe William H. , Bennett John M. , Tsiatis Anastasios A. , Oken Martin M.
Published: February 2007

In order to assess the efficacy and toxicity of dexamethasone as a single agent without the concomitant infusion of Adriamycin and vincristine (VAD), an ECOG pilot study was initiated using 40 mg by mouth daily for 4 days every week for 8 weeks. Patients who responded were then maintained on the same treatment, but at 2 week intervals. Of the 32 patients evaluable for response, three were completely refractory to all prior therapy. All patients had advanced disease and 26 had received multiple prior treatments. There were 13/32 (40%) objective responses by ECOG criteria. Of the 28 patients evaluable for subjective response, i.e., significant decrease in performance status and/or bone pain, eight (28.5%) responded. Of the 34 patients evaluable for toxicity, 19 patients (55%) had moderate to severe side effects, including nine who had central nervous system effects, three who had gastrointestinal bleeding, two who had pulmonary emboli, one with psychosis, and four who had serious infections with one death. Median survival for the entire group was 19 weeks, with 31 weeks in the responders and 9 weeks in the non‐responders.

Although high‐dose dexamethasone is capable of producing a significant number of partial responses (40%), it is associated with excessive toxicity. Less frequent administration of the dexamethasone at 2 week intervals was well tolerated in the maintenance of partial response, but has not been studied for efficacy in induction of remission.
Effect of β‐Globin gene cluster haplotype on the hematological and clinical features of sickle cell anemia
Authors: Rieder R. F. , Safaya S. , Gillette P. , Fryd S. , Hsu H. , Adams J. G. , Steinberg M. H.
Published: February 2007

In 113 black American adults with sickle cell anemia (HbSS), we examined nine polymorphic restriction sites, including the Xmnl site 5' to the Gγ gene, to see whether haplotype is related to the level of HbF and the proportion of Gγ chains or if it influences the hematological and clinical features of the disease. Seventy‐five percent of the patients were homozygous or heterozygous for the Benin (no. 19) or Central African Republic (Bantu, no.20) haplotypes; 13.3% were homozygous fo heterozygous for the Senegal (no.3) haplotype, while 11.5% had other genotypes. Of the subjects, 14.2% were either homozygous or heteroxygous for the Xmnl restriction site 5' to the Gγ gene. We found no effect of haplotype on HbF levels. The level of Gγ chains was 60.5% ± 17.0% in individuals with other haplotypes. Subjects with the Xmnl site 5' to the Gγ gene had Gγ globin levels of 59.5% ± 16.7% while those lacking that site had an average of 47.2% ± 12.1%. There were no significant differences among these groups in hemoglobin concentration, packed cell volume, mean cell volume, or haplotype 3 and the 5' G γ Xmnl site were associated with increased Gγ chains, there was no effect on HbF level or other hematological and clinical features that might reflect disease severity. It is likelu that determinants unrelated to haplotype, linked or unlinked to the β‐globin gene cluster, are the major effectors of differences in the levels of HbF in American patients with sickle cell anemia.
Transient anticardiolipin antibodies, functional protein S deficiency, and deep vein thrombosis
Authors: Sthoeger Z. M. , Sthoeger D. , Mellnick S. D. , Steen D. , Berrebi A.
Published: February 2007

A 30‐year‐old man presented with an episode of deep vein thrombosis. He was found to have primary antiphospholipid syndrome with anticardiolipin antibodies and protein S deficiency. All other investigations were negative. Three months later, anticardiolipin antibodies were negative and protein S levels were normal. The transient presence of anticardiolipin antibodies and functional protein S deficiency in this patient suggests a new mechanism for the association between anticardiolipin antibodies and venous thrombosis.
Continuous infusion of monoclonal antibody‐purified factor VIII
Authors: Weinstein Ralph E. , Bona Robert D. , Rickles Frederick R.
Published: February 2007

Continuous intravenous infusion of wet and dry heat treated factor VIII products has been shown to be an effective, safe, and convenient alternative to pulse‐dose therapy for the treatment of patients with hemophilia.

We have used 12‐hr, single‐bottle continuous infusion of a factor VIII product purified from plasma sources by the use of monoclonal antibodies (Monoclate; Rorer Pharmaceutical Company) for the treatment of four bleeding episodes in three patients with severe hemophilia A. Patients required 2.1 U/kg/hr to attain an in vivo factor VIII level of 50 U/dl. Clinical hemostasis was achieved for all treatment episodes and no untoward effects of therapy were noted. Stability of the factor VIII:C levels in the product in vitro was also demonstrated.

We conclude from this preliminary data that continuous infusion of factor VIII products purified by monoclonal antibody technology is a safe, effective, and practical approach to the treatment of patients with hemophilia A.
Severe and fatal anthracycline cardiotoxicity at cumulative doses below 400 mg/m2: Evidence for enhanced toxicity with multiagent chemotherapy
Authors: Watts Raymond G.
Published: February 2007

Three cases of severe, progressive, and in two cases, fatal cardiomyopathy secondary to anthracycline chemotherapy are reported. All of the patients were receiving multiagent chemotherapy for extremity sarcomas consisting of doxorubicin, high‐dose methotrexate, bleomycin, cyclophosphamide, dactinomycin, and cisplatinum at the onset of their congestive heart failure. Cardiomyopathy developed in each patient at cumulative anthracycline doses <400 mg/m2. These cases suggest that enhanced cardiotoxicity may occur when anthracyclines are used in combination with other agents such as cyclophosphamide, bleomycin, cisplatinum, and methotrexate and that cumulative anthracycline doses considered to be “safe” may need to be lowered in these circumstances.
Treatment of aplastic anaemia with antilymphocyte globulin and high‐dose methylprednisolone
Authors: Novitzky Nicolas , Wood Lucille , Jacobs Peter
Published: February 2007

Twenty‐three consecutive adults with bone marrow aplasia who, apart from one individual, lacked a sibling suitable for allogeneic transplantation, received five daily infusions of 50 mg/kg of antilymphocyte globulin (ALG) concurrently with high‐dose (500 mg) methylprednisolone (HDMP), followed by oral prednisone at a dose of 30 mg until day 30. One patient died early so that response could not be determined, but data are available and included in the toxicity as well as survival analysis. Haematological response occurred in 13 of the remaining 22 (59%). This followed a single course of treatment in 12, with complete response achieved in five of this group and a second course required in one. At a median follow‐up of 20 months (range 5–60), there have been five relapses and 13 patients are alive, including 12 responders who have Karnofsky ratings between 90% and 100%. Of the other nine individuals, only two are alive, with 1 at 12 months still requiring active support and the second, after failing further courses of treatment, at 41 months having a partial response to lymphocytapheresis and plasma exchange. Failure to respond was a significant adverse predictor for survival (P=0.022). This study involved two distinct batches of ALG, with response occurring in 1/7 (14%) patients treated with the first lot, but in 12/15 (80%) of those individuals who were treated with the second (P=0.007). Only a pretreatment mean cell volume (MCV) greater than 100 fL predicted for response (P=0.0088). Confirmation is hereby provided for the efficacy of ALG used in combination with HDMP for treatment of aplastic anaemia, with further support for the observation that not all batches of this product are comparable in bringing about haematologic response in these individuals.
Detection of primary epstein‐barr virus infection in a patient with x‐linked lymphoproliferative disease receiving immunoglobulin prophylaxis
Authors: Okano Motohiko , Bashir Rifaat M. , Davis Jack R. , Purtilo David T.
Published: February 2007

Serologic diagnosis for Epstein‐Barr virus (EBV) infection is problematic when patients receive exogenous immunoglobulin. We recently diagnosed primary EBV infection by detecting EBV‐determined nuclear antigen (EBNA) and EBV‐DNA in peripheral blood mononuclear cells (PBMC) using immunofluorescence, in situ hybridization and polymerase chain reaction (PCR) techniques in a patient with X‐linked lymphoproliferative disease (XLP) who received prophylactic immunoglobulins for EBV infection. These combined techniques may be helpful for early and accurate diagnosis of EBV infection in highly vulnerable patients.
Disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system in systemic lupus erythematosus
Authors: Ruiz‐Argüelles Guillermo J. , Ruiz‐Argüelles Alejandro , Lobato‐Mendizábal Eduardo , Díaz‐Gomez Felipe , Pacheco‐Pantoja Elda , Drenkard Cristina , Alarcón‐Segovia Donato
Published: February 2007

Increased thrombogenesis observed in systemic lupus erythematosus (SLE) is derived from multiple mechanisms, including: Enhanced coagulation factor VIII:VWf activity, lupus anticoagulants, anti‐phospholipid antibodies, acquired deficiencies of natural anti‐thrombotic mechanisms (protein C, protein S, anti‐thrombin III), and impaired fibrinolytic mechanisms. We studied the fibrinolytic mechanisms of 18 patients with systemic lupus erythematosus, selected carefully to avoid other possible causes of abnormalities in the fibrinolytic activity. Despite the fact that the euglobulin lysis time in steady state was normal in all instances, disturbances in the tissue plasminogen activator/plasminogen activator inhibitor (TPA/PAI) system were found in all SLE patients: TPA activity was undetectable in all cases, whereas it was above 0.4 IU/ml in a control group. In 72 percent of patients, the undetectable TPA activity was correlated with abnormally high PAI activity; PAI levels were normal in all members of the control group, their mean value being 0.74 versus 8.63 IU/ml for SLE patients (P < .01). Coagulation protein C deficiency was found in 3 patients (17%). Even though within normal range, fibrinogen levels were significantly higher in SLE than in normal controls (219 versus 192 mg/dl, P < .01) and plasminogen levels were significantly higher in SLE than in controls (117 versus 78.2%, P < .01). Cross‐linked fibrin derivatives (D‐D dimers) were negative in all patients with SLE. Sixty‐eight percent of SLE patients had high levels of antiphospholipid antibodies, but no correlation with the disturbances of the TPA/PAI system was found. It is concluded that most patients with SLE display severe abnormalities in the TPA/PAI anti‐thrombotic system and that these abnormalities may be related to the lupus thrombophilia, apparently multifactorial in its origin.
Non‐hodgkin lymphoma in common variable immunodeficiency
Authors: Cunningham‐Rundles C. , Lieberman P. , Hellman G. , Chaganti R. S. K.
Published: February 2007

The association between cancer and immunodeficiency is well established. In common variable immunodeficiency (CVI), a primary immunodeficiency disease characterized by low serum immunoglobulins and poor antibody production, we previously reported a total of 13 cancers in 11 individuals arising in continuously observed group of patients. Of the 13, 7 were NHL and 1 was a myeloma which progressed to lymphoma. We report here the histologic, immunologic, cytogenetic, and clinical features of these 8 NHL along with 3 new lymphomas which have appeared in this group (now 117 patients). From our studies, the lymphomas which have arisen in CVI share certain features with the lymphomas which appear in the childhood immunodeficient syndromes, Wiskott Aldrich Syndrome, Ataxia Telangiectasia, or severe combined immunodeficiency: they are similar in overall frequency (13%), are often B‐cell in origin, and extranodal in location. However, unlike the lymphomas of the immunodeficient child, lymphomas in CVI may be more differentiated and secrete immunoglobulin. For CVI patients with stage I or II disease, as for non‐Hodgkin lymphomas in general, the prognosis is good. In our group, NHL in CVI have appeared most often in females of the 5th to 7th decade and not in childhood. Cytogenetic studies in lymphomas show that cytogenic abnormalities, including chromosomal translocation, can be found in this group, but more studies will be needed to assess the frequency of these events.
Reversible bone marrow hypoplasia induced by alcohol
Authors: Nakao Shinji , Harada Mine , Kondo Kunio , Mizushima Noriaki , Matsuda Tamotsu
Published: February 2007

A 51‐year‐old man developed severe pancytopenia with bone marrow hypoplasia after consuming excessive amounts of alcohol for many years. After avoiding alcohol and eating normally for about 10 days, his blood cell counts promptly recovered to near‐normal levels. Hematologic remission had lasted for 7 months until he began to drink alcohol excessively again, leading to a relapse of pancytopenia with marrow hypoplasia. His blood cell counts attained near‐normal levels again after abstaining from alcohol for about a month. He developed thrombocytopenia following moderate ingestion of alcohol 7 months later, but he never developed severe pancytopenia after limiting alcohol ingestion. When bone marrow mononuclear cells from the patient and normal volunteers were cultured in the presence of ethanol, CFU‐GM‐derived colony formation of the patient was inhibited by much lower concentrations of ethanol than that of normal volunteers. The clinical course of the patient and the greater sensitivity of the patient's CFU‐GM to ethanol toxicities indicate that massive intake of alcohol was responsible for bone marrow hypoplasia observed in this patient.
Venous insufficiency is not the cause of leg ulcers in sickle cell disease
Authors: Billett H. H. , Patel Y. , Rivers S. P.
Published: February 2007

Leg ulcers are a well recognized complication of sickle cell disease that has been attributed to venous insufficiency. We studied 16 patients with sickle cell disease and active ulcers using venous pulse volume recordings and photoplethysmography (Doppler studies). Based on hemodynamic monitoring, all 16 patients exhibited rapid refilling times, findings that Imply venous Insufficiency but are also compatible with high‐output syndrome or arteriovenous shunting. Direct invasive venous pressure measurements of these patients demonstrated normal pressures in all of the four patients tested. A different set of four patients underwent venography, which also failed to demonstrate venous incompetence. We hypothesize that anemia results in an increase in peripheral arteriovenous shunting in the extremities and that this, together with the high‐output syndrome of sickle cell disease, produces plethysmography readings that may be confused with findings observed in venous insufficiency. We conclude that measurements of vascular stasis, as recorded by plethysmography, are usually misinterpreted in sickle cell disease. Normal manometric pressure readings and normal venographic studies suggest that venous insufficiency is not a primary factor in sickle cell leg ulcer formation.
Plasma level of tumor necrosis factor in disseminated intravascular coagulation
Authors: Wada Hideo , Ohiwa Michiaki , Kaneko Toshihiro , Tamaki Shigehisa , Tanigawa Motoaki , Takagi Mikio , Mori Yoshitaka , Shirakawa Shigeru
Published: February 2007

The plasma level of tumor necrosis factor (TNF) was determined in 20 normal individuals, 52 patients with disseminated intravascular coagulation (DIC), 22 pre‐DIC patients, and 39 non‐DIC patients. TNF was not detected in the normal subjects, and the level was very low in non‐DIC patients. However, the TNF level was significantly elevated in DIC patients, and it was moderately increased in pre‐DIC patients shortly before the onset of DIC. This increase in circulating TNF may be associated with DIC. TNF was higher in DIC associated with solid cancer than in DIC associated with leukemia or sepsis. The increase in plasma TNF level was mildly correlated with DIC score, and it was significantly increased in patients with poor prognosis. However, the plasma TNF level in DIC patients with organ failure was not significantly different from those without organ failure. We conclude that the increase in circulating TNF reflects the pathogenic factors in DIC rather than being a consequence of organ failure due to DIC.
Transient erythroblastopenia in the first year of life
Authors: Ware Russell E. , Kinney Thomas R.
Published: February 2007

The distinction between transient erythroblastopenia of childhood (TEC) and congenital red cell aplasia (Blackfan‐Diamond anemia) is usually possible at presentation using clinical and laboratory data. When hypoplastic anemia occurs in the first year of life, however, the distinction is more difficult. We describe 7 infants with hypoplastic anemia who illustrate this diagnostic dilemma.
Successful treatment of a patient with postpartum factor VIII inhibitor with recombinant human interferon α 2a
Authors: Schwerdtfeger R. , Hintz G. , Huhn D.
Published: February 2007

A patient who had developed a postpartum inhibitor to factor VIII and who did not respond to repeated therapy with steroid and high‐dose intravenous gammaglobulin G was treated with one short course of low‐dose recombinant interferon α 2a (rhlFN) s.c. Within 7 weeks from the start of rhlFN treatment, the inhibitor disappeared. It remains undetectable 8 months after therapy.
Warfarin skin necrosis: Recurrence in the absence of anticoagulant therapy
Authors: Humphries John E. , Gardner James H. , Connelly Julia E.
Published: February 2007

Skin necrosis is a well‐known yet rare complication of oral anticoagulant therapy. We report the unusual recurrence of lesions typical of warfarin skin necrosis in the absence of anticoagulant therapy. A 59‐year‐old woman developed skin necrosis while receiving prophylactic warfarin following the detection of a large left ventricular thrombus. The warfarin was discontinued and the lesions improved. One month later new areas of skin necrosis developed although the patient had received no further warfarin. Progressive congestive heart failure, poor nutrition, and prolonged oral antibiotic therapy preceded the recurrence. Vitamin K deficiency was present on admission. The potential role of vitamin K‐dependent coagulation factors in the pathogenesis of anticoagulant‐associated skin necrosis is discussed.
Preliminary report on the use of desferrioxamine in the treatment of Plasmodium falciparum malaria
Authors: Traore Ousmane , Carnevale Pierre , Kaptue‐Noche Lazar , M'Bede Joseph , Desfontaine Michel , Elion Jacques , Labie Dominique , Nagel Ronald L.
Published: February 2007

The administration of 0.5 g (IM) of desferrioxamine every 12 hr for 3 days with 25 mg/kg (total dose for three days) of chloroquine abated the parasitemia of Plasmodium falciparum infected individuals more rapidly than chloroquine alone. Two patients with in vitro evidence of total or partial resistance to chloroquine also were successfully treated with the combination of drugs, and were free of parasitized red cells by day 7. Further clinical trials and development of desferrioxamine in the treatment of P. falciparum are warranted.
Enhanced expression of poly(ADP‐ribose) synthetase gene in malignant lymphoma
Authors: Tomoda Takashi , Kurashige Takanobu , Moriki Toshiaki , Yamamoto Hiroshi , Fujimoto Shigeyoshi , Taniguchi Taketoshi
Published: February 2007

Over‐expression of cellular protooncogenes has been proposed to function in the initiation and maintenance of malignancies. In order to distinguish malignant lymphoma from reactive proliferative diseases, we surveyed the expression levels of three protooncogenes(c‐myc, c‐fos and c‐myb) in malignant lymphoma and reactive proliferative diseases. An increased level of c‐myc or c‐fos mRNA was observed in one case, respectively, out of three malignant lymphomata. The other cases exhibited no enhancement in protooncogenes. These oncogenes are critically regulated during differentiation, but the half‐life of c‐myc mRNA was very short, and the level of the mRNA decreased to the initial level very quickly. Thus, the high level of the expression of these oncogenes may not always be maintained in all malignant cells. We then examined the level of mRNA for poly(ADP‐ribose) synthetase in those cases. An enhanced expression for the synthetase gene was observed in all five malignant lymphomata tested, but no increase in the level of the mRNA was observed in any reactive proliferative cases or normal lymph nodes. These results suggest that enhanced expression of poly(ADP‐ribose) synthetase gene seems to be a common characteristic of protopathic malignant lymphoma. By using the characteristics of malignant lymphoma, the level of mRNA for the synthetase may be applicable for differential diagnosis of malignant lymphoma from several pathologically indistinguishable diseases.
Fibrinogen date: Congenital hypodysfibrinogenemia associated with decreased binding of tissue‐plasminogen activator
Authors: Ieko Masahiro , Sawada Ken‐Ichi , Sakurama Shoki , Yamagishi Ikuko , Isogawa Shin , Nakagawa Shoichi , Satoh Masahiro , Yasukouchi Taro , Matsuda Michio
Published: February 2007

A new case of congenital hypodysfibrinogenemia associated with a thrombotic tendency (thrombosis of the peroneal artery, the pulmonary artery and the deep veins of the lower extremities), is reported. Clotting time using Reptilase was significantly prolonged. The low levels of plasma fibrinogen were demonstrated using both thrombin time (Clauss) method (45.0 mg/ml) and radial immunodiffusion technique (106.1 mg/ml). The fibrinogen is also characterized by a defective polymerization of fibrin monomers. Furthermore, the important functional property of this fibrinogen is that the patient's fibrin adsorbs approximately 31–38% of added tissue‐plasminogen activator (t‐PA) at the time of fibrin formation, whereas control fibrin can adsorb about 79% of added t‐PA. This result could provide an explanation for the thrombotic tendency in this patient. This variant fibrinogen appears to have unique characteristics and has been designated as “Fibrinogen Date,” according to the city where the proband has lived.
Anticardiolipin antibodies (ACA) are most often not associated with lupus‐like anticoagulant (LLAC) in human immunodeficiency virus (HIV) infection
Authors: Capel P. , Janssens A. , Clumeck N. , Gerard M. , Feremans W. , Vandevelde D. , Fondu P.
Published: February 2007

Anticardiolipin antibodies (ACA) and lupus‐like anticoagulant (LLAC) have been studied in a group of 142 non‐hospitalized and a group of 72 hospitalized HIV infected patients. We observed a variable frequency of ACA positivity ranging from 7.7% to 30.3% according to the groups of patients and the isotype of immunoglobulin fraction containing ACA activity. None of the patients investigated presented a prolongation of the activated partial thromboplastin time (APTT) compatible with the presence of a LLAC. Some patients presented a weak anticoagulant activity only detected by the tissue thromboplastin inhibition (TTI) test. No positive correlation was found between this latter test and ACA. We conclude that, like in syphilitic patients, ACA present in HIV infected patients are most often not associated with LLAC.
Hepatocellular carcinoma in hemophilia
Authors: Colombo M. , Mannucci P. M. , Brettler Doreen B. , Girolami A. , Lian E. C. Y. , Rodeghiero F. , Scharrer Inge , Smith P. S. , White G. C.
Published: February 2007

A questionnaire‐based survey Involving 11,801 hemophiliacs from 54 hemophilia centers in the USA and Europe documented the occurrence of hepatocellular carcinoma(HCC) in 10 patients. The crude rate of HCC was 3.2/100,000 patients/year, at least 30 times higher than the background incidence of this tumor in the countries of origin of the patients. All patients were Caucasians with hemophilia A, 39 to 74 years of age, and had liver cirrhosis. All had one or more risk factor for cirrhosis and HCC: 5 were positive for serum hepatitis B surface antigen, 4 had the antibody to hepatitis C virus, and 4 had histories of alcohol abuse. Serum alpha‐fetoprotein, measured in 6 patients, was significantly elevated in 4 (range: 807‐1399 ng/ml), and only moderately elevated in 2 (25 and 171 ng/ml). The onset of HCC was asymptomatic in 5 patients, whereas it was accompanied by jaundice, abdominal pain, or ascites in the remaining patients. Thus, HCC seems to be a more important secondary disease for hemophiliacs than formerly recognized. Since HCC is often asymptomatic, screening hemophiliacs with chronic liver disease with periodic ultrasound scans might increase the chances of detecting HCC at a stage amenable to surgical treatment.
Therapeutic implications and sites of relapse predicted by elevated posttherapy erythrocyte sedimentation rate in early stage Hodgkin disease
Authors: Friedman Samuel , Henry‐Amar Michel , Cosset Jean‐Marc , Carde Patrice , Hayat Marcel , Dupouy Noelle , Tubiana Maurice
Published: February 2007

An analysis was performed of all 57 early relapses (ER) (within 18 months of therapy initiation) seen in a group of 301 patients treated on three successive European Organization for Research and Treatment of Cancer (EORTC) protocols from 1964 to 1981; to determine whether a posttherapy elevated erythrocyte sedimentation rate (ESR) (⩾30mm) could predict the type of relapse and the effect upon the relapse of different therapies received. Overall most ER occurred in extranodal (EN) (42%) or irradiated transdiaphragmatic nodal (TDN) (40%) sites. Compared to patients with normal posttherapy ESR (n = 12), patients with elevated posttherapy ESR (n = 45) had the same proportions of outfield and late relapses; more frequent multiple sites of ER (38% vs. 25%), increased proportions of early EN relapses (16% vs. 3%), TDN relapses (17% vs. 2%), and other ER (6% vs. 1%). ER were most frequently observed between 1964 and 1971, and “modern” radiotherapy (Rt) decreased ER overall from 27% to 13% and for elevated posttherapy ESR patients from 54% to 25%. When chemotherapy (Ct) was used as either adjuvant or initial therapy, ER were greatly reduced vs. Rt alone [overall (6% vs. 28%) and for patients with elevated posttherapy ESR (10% vs. 39%)]. Stepwise logistic regression showed Ct to be the most important factor “protecting” from EN relapse, but elevated posttherapy ESR was still significant. For early TDN relapse, elevated posttherapy ESR had the highest predictive value for relapse, greater than the types of radiation fields used and chemotherapy. An unexplained elevated posttherapy ESR, regardless of previous therapy, predicts for ER from aggressive HD, frequently in EN and irradiated areas, and warrants further early therapy.
Suppressed natural killer cell activity in patients with chronic autoimmune thrombocytopenic purpura
Authors: Semple John W. , Bruce Suzanne , Freedman John
Published: February 2007

Natural killer (NK) cell activity was studied in 17 patients with primary chronic idiopathic autoimmune thrombocytopenic purpura (ATP). Fifteen of 17 patients had a significantly reduced NK cytotoxicity against 51chromium labeled K562 target cells (mean LU20% = 18 ± 20 in patients versus 65 = 2 5 in controls, P < 0.001). NK activity was also significantly reduced in all of six patients with secondary ATP as compared with normal controls (LU20%28±15, respectively, P < 0.005). The NK activity in both patient groups correlated with the duration of therapy being received (r = 0.60, P < 0.001). Immunophenotypic analysis of peripheral blood mononuclear cells from patients with ATP revealed that CD8‐ cells bearing CD57 (HNK‐1, Leu 7) and CD3‐ cells bearing CD56 (Leu 19) were quantitatively within the normal range. These findings indicate that patients with ATP have a functional defect in NK cytolytic activity.
Granulocyte‐macrophage colony stimulating factor for the treatment of drug induced agranulocytosis
Authors: Nand Sucha , Bayer Robert , Prim Richard A. , Felten William , Godwin John E.
Published: February 2007

Drug induced agranulocytosis is an uncommon but potentially fatal complication. In some cases, it may be associated with hypoplasia and depletion of granulocytic precursors in the marrow, leading to prolonged neutropenia. We report on the use of granulocytic‐macrophage colony stimulating factor (GM‐CSF) in two such cases, at a dose of 10 μg per kilogram per day subcutaneously. The absolute neutrophil count rose above 500/mm3 in 3 days in both cases. We believe that GM‐CSF expedited the recovery of granulocyte counts in our patients and warrants further study in the management of drug induced neutropenia.