摘要:

AbstractFactor VIII (FVIII) replacement by continuous infusion has been advocated as a cost‐effective method for maintaining stable plasma levels of FVIII in the hemophilia A patient during surgery or life‐threatening hemorrhage. Continuous delivery of monoclonal or recombinant FVIII concentrates to our pediatric patients using a traditional delivery system (dilution in normal saline of 2–10 U/ml infused at a rate of 20 ml/hr) has frequently yielded higher than expected factor usage to achieve desired levels and unexpected variability in plasma levels under presumed steady‐state conditions. To determine if diminished in vitro FVIII recovery was responsible for these observations, a study of four ultrapure concentrates during 8 hr of in vitro continuous delivery was performed using four delivery systems. When reconstituted concentrate was added to normal saline in polyvinylchloride bags at a concentration of 10 U/ml (method IA), monoclonal products showed a stable recovery of 84–109% of time 0 levels. Recombinant product recovery dropped to 57–76% of time 0 levels before reapproximating the time 0 level at 2 hr. The addition of 10 mg/ml human albumin to the bags (method IB) did not improve recoveries. When reconstituted concentrate was delivered undiluted (method IIA), the early drop in recombinant recovery was eliminated; stable recovery of 78–117% of time 0 level was achieved with all products. In using method IA, a large discrepancy was seen between the actual time 0 recoveries and those expected based on vial assays, most striking for recombinant products (49–57% of expected). Method IIA allowed 75–90% recovery; addition of 20 mg/ml albumin of reconstituted but undiluted concentrate (method IIB) maximized recovery at 85–98% of expected. ©

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199602)51:2<99::AID-AJH1>3.0.CO;2-1

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractForty‐two cytomegalovirus (CMV)‐seropositive allogeneic marrow transplant patients or recipients of CMV‐seropositive marrow allografts were entered into a surveillance program to detect and treat CMV infection during the first 120 days posttransplant. CMV infection was detected at a mean time of day 50 in 21/37 (58%) patients who had surveillance cultures. Twelve of 42 (28%) received preemptive ganciclovir treatment for virus isolated from blood (9 patients) or from bronchoalveolar lavage fluid (3 patients), and all had no CMV‐associated sequelae. CMV disease was diagnosed in 5 patients (4 with pneumonia, 1 with gastroenteritis) who did not have positive cultures until the onset of their disease. CMV‐related mortality was 4/42 (10%). Patients who earlier manifested lung injury or diffuse alveolar hemorrhage (DAH) were significantly predisposed to subsequent CMV pneumonia (P= 0.0013, Fisher's exact test) at a median onset of day 42. Restricted prophylactic use of ganciclovir in such patients may be indicated. Fifty percent of all patients never required ganciclovir during the surveillance period. When compared to a universal prophylaxis program of ganciclovir for the prevention of CMV disease, the use of ganciclovir in a preemptive strategy could avoid unnecessary therapy for a substantial number of patients and earn significant cost‐savings. © 1996 Wil

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199602)51:2<104::AID-AJH2>3.0.CO;2-1

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractSevere pruritus is frequently associated with myeloproliferative and other systemic illnesses, and often fails to respond to conventional measures. We used danazol (Danocrine™), a synthetic attenuated androgen, in the treatment of severe pruritus refractory to conventional therapy. Eight patients had myeloproliferative disorders (MPD), seven had autoimmune disorders, and seven had skin diseases. Danazol at 400–800 mg/day was administered, and previous medications were tapered off. When itching was controlled with danazol alone, the dosage was reduced or discontinued, and resumed if itching recurred. Clinical responses were graded, and side effects were monitored. Overall, in 12 of 22 patients refractory to other measures, itching was controlled with danazol alone. In 10 patients itching returned when danazol was discontinued or dosage was reduced, and was relieved upon resumption or increase of dosage. Danazol therapy was continued for up to 5 years in responders. No serious side effects were observed. Our experience indicates that danazol is a good alternative for patients with severe pruritus associated with myeloproliferative and other systemic disorders. © 1996 Wiley‐Lis

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199602)51:2<112::AID-AJH3>3.0.CO;2-0

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

Abstract5‐azacytidine (5‐AZA) and carboplatin (CBDCA) are two agents which have demonstrated antileukemic activity in a number of phase I‐II trials. Their mechanisms of action and pharmacology related to cell resistance suggested suitability for combination therapy. The aim of this pilot study was to evaluate the effects of this combination in the treatment of patients with relapsed/refractory acute leukemia. A total of 21 patients was enrolled. 5‐azacytidine, at doses ranging from 50–150 mg/m2/day, was administered as a 2‐hr infusion for 5 consecutive days. On day 3, patients began a 5‐day course of CBDCA given as a 24‐hr continuous intravenous infusion of 250 mg/m2/day. There were no complete remissions with this regimen. Although there were three partial responses, these were generally of short duration. Nonhematologic toxicities were mild. No correlation was seen between response and serum platinum levels. These results demonstrate that the 5‐AZA/CBDCA combination is ineffective therapy for heavily pretreated patients with acute leukemia. © 19

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199602)51:2<117::AID-AJH4>3.0.CO;2-0

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractMolecular abnormalities of erythroenzymopathies associated with hereditary hemolytic anemia have been determined by means of molecular biology. Pyruvate kinase (PK) deficiency is the most common and well‐characterized enzyme deficiency in the glycolytic pathway, and it causes hereditary hemolytic anemia. To date, 47 gene mutations have been identified. We identified one base deletion, one splicing mutation, and six distinct missense mutations in 12 unrelated families with a homozygous PK deficiency. Mutations located near the substrate or fructose‐1,6‐diphosphate binding site may change the conformation of the active site, resulting in a drastic loss of activity and severe clinical symptoms. Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency is the most common metabolic disorder, and it is associated with chronic hemolytic anemia and/or drug‐or infection‐induced acute hemolytic attack. An estimated 400 million people are affected worldwide. The mutations responsible for about 78 variants have been determined. Some have polymorphic frequencies in different populations. Most variants are produced by one or two nucleotide substitutions. Molecular studies have disclosed that most of the class 1 G6PD variants associated with chronic hemolysis have the mutations surrounding either the substrate or the NADP binding site. Among rare enzymopathies, missense mutations have been determined in deficiencies of glucosephosphate isomerase, phosphofructokinase (PFK), aldolase, triosephosphate isomerase (TPI), phosphoglycerate kinase, and adenylate kinase. Compound heterozygosity with missense mutation and base deletion has been determined in deficiencies of hexokinase and diphosphoglyceromutase. Compound heterozygosity with missense and nonsense mutations has been identified in TPI deficiency. One base deletion resulting in a frameshift and the premature termination of translation and splice junction mutations resulting in abnormally spliced PFK‐M mRNA have been identified in homozygous PFK deficiency. An exception is hemolytic anemia due to increased adenosine deaminase activity. The basic abnormality appears to result from the overproduction of a structurally normal enzyme. © 1996

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199602)51:2<122::AID-AJH5>3.0.CO;2-#

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractWe report a case of severe priapism occurring in a patient with an unstable hemoglobin, Hb Olmsted (β141 Leu→Arg). This is a rare hemoglobin variant, which until now has been reported only once. The clinical course of the 12‐year‐old boy was characterized by severe hemolytic anemia leading to splenectomy and cholecystectomy at the age of 3.5 years. The priapism occurred 8 years after splenectomy, during a hemolytic febrile episode and required aspiration of the corpora cavernosa. This report raises the question of the benefit of splenectomy in patients suffering from a chronic hemolytic anemia such as that due to an unstable hemoglobin. This treatment lowers the frequency and the severity of acute hemolytic attacks, but several cases of vascular complications have been reported after splenectomy. © 1996 Wiley‐

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199602)51:2<133::AID-AJH6>3.0.CO;2-Z

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractEssential thrombocythemia (ET) is an uncommon myeloproliferative disorder, which is thought to develop from a multipotent stem cell. Like other myeloproliferative diseases, ET is associated with an increased risk of development of acute leukemia (AL). However, the large majority of cases of leukemic transformation in ET are thought to be related to prior therapy, usually radioactive phosphorous or alkylating chemotherapy, and the development of AL in ET is extremely rare in the untreated patient. In this report, two cases of ET which evolved into AL without prior exposure to radiation or alkylating agents, and which were treated with long‐term hydroxyurea therapy, are described. The first case had cytogenetic changes in the bone marrow suggestive of therapy‐associated leukemia, and the second developed myelodysplastic syndrome on therapy which was likely chemotherapy‐induced and led to acute leukemia. Prolonged used of hydroxyurea in patients with ET may lead to therapy‐associated acute leukemia. © 1996 Wiley

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199602)51:2<137::AID-AJH7>3.0.CO;2-Z

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractWe describe a patient who has a chronic polyclonal B lymphocyte proliferation with a hairy‐cell appearance. A 48‐year‐old Japanese woman with marked splenomegaly, systemic lymphadenopathy, and leukocytosis was referred to our hospital. Laboratory examination revealed marked polyclonal IgG hypergammaglobulinemia. Morphologic examination of the patient's peripheral blood, including May‐Glemsa staining and scanning electron microscopy, showed a monotonous proliferation of hairy‐appearing mature lymphocytes. An immunophenotypic study revealed an expansion of cells with mature B cell antigens positive for CD11c; however, light‐chain restriction was not seen. The lack of both immunoglobulin heavy‐chain and T cell receptor gene rearrangements by Southern blot analysis indicated the polyclonal nature of the proliferating B cells. This was confirmed further by a clonal analysis of the patient's lymphocytes using an X‐chromosome‐linked restriction fragment polymorphism within the X‐linked phosphoglycerate kinase (PGK) gene. Since chronic B cell lymphoproliferation with a hairy cell appearance has not been described previously, this case might be extremely rare, and has important implications for the pathogenesis of mature B cell lymphoproliferative diseases, including hairy cell leukemia. ©

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199602)51:2<141::AID-AJH8>3.0.CO;2-Y

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractThe French‐American‐British (FAB) classification of acute leukemias is based on the light microscopic detection of myeloperoxidase (MPO) activity in blast cells. Cells with MPO activity in>3% of cells are classified as acute myeloid leukemia (AML) and usually express myeloid cell surface antigens. We describe a case of acute leukemia in which the blast cells have lymphoid morphology, ultrastructure, immunophenotype, and molecular rearrangements, but express significant amounts of MPO. We discuss the incidence, features, and outcome of MPO‐positive acute lymphoblastic leukemia (ALL). © 1996 Wiley‐L

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199602)51:2<147::AID-AJH9>3.0.CO;2-Y

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY

摘要:

AbstractAlthough suramin has long been used to treat human trypanosomiasis, recent clinical trials have tested its efficacy against the acquired immunodeficiency syndrome (AIDS) and various malignancies. Thrombocytopenia was observed in early trials with suramin in AIDS, but has been uncommon in patients treated for solid tumors. Here we describe 5 patients out of a total of 67 (7%) who developed severe thrombocytopenia while receiving suramin as part of a phase II clinical trial for metastatic prostate carcinoma refractory to hormonal therapy. IgG purified from one patient's plasma caused suramin‐dependent platelet aggregation. There was also evidence of crossreactivity between suramin and heparin in this system. An immune mechanism, however, could not be documented in the other cases, suggesting that multiple mechanisms may be responsible for severe thrombocytopenia in this patient population. (This article is a US Government work and, as such, is in the public domain in the United States of America.) © 1996 Wiley‐Liss,

ISSN:0361-8609    

DOI:10.1002/(SICI)1096-8652(199602)51:2<152::AID-AJH10>3.0.CO;2-K

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1996

数据来源: WILEY