bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality in immune thrombocytopenic purpura: Report of seven cases and consideration of prognostic indicators
Authors: Schattner Elaine , Bussel James 
Published: February 2007

AbstractITP (Immune thrombocytopenic purpura) is generally considered a benign disease. Despite what may be severe thrombocytopenia, most patients with ITP do not suffer significant bleeding episodes. Mortality is rare, and the majority of cases are managed successfully with conventional treatments. For patients who maintain a platelet count of > 20,000/μl, aggressive immunosuppressive therapy is usually unwarranted.There are some patients with ITP who are at increased risk of serious morbidity and mortality from their disease. Fatal cases of ITP are rarely mentioned in published reports. In this study we review the incidence of mortality and describe the deaths of seven patients with ITP, with the aim of identifying and improving management of high‐risk cases.Based on our review of the literature and analysis of cases at our institution, fatal cases of ITP fall into three groups: death from intracranial hemorrhage with severe thrombocytopenia, death after splenectomy, and death due to infection after cytotoxic treatments. Patients who appear to carry increased risk include: 1) older patients; 2) chronic, refractory patients with a history of hemorrhage; and 3) patients with concomitant bleeding diatheses such as uremia and hemophilia. © 1994 Wiley‐Liss, Inc.
Systematic use of automated fluorescence‐based sequence analysis of amplified genomic DNA for rapid detection of point mutations
Authors: Tamary H. , Surrey S. , Kirschmann H. , Shalmon L. , Zaizov R. , Schwartz E. , Rappaport E. F. 
Published: February 2007

AbstractSeveral approaches are now available for screening populations for known mutations in a given gene. However, for detection of multiple mutations in a population that has not been characterized or for detection of new mutations, the value and efficiency of these screening procedures decreases. Although more than 100 different β‐thalassemia mutations have so far been described, the spectrum of mutations in the Eastern Mediterranean and Israel has not been defined in detail. We have used automated fluorescence‐based DNA sequence analysis of PCR‐amplified genomic DNA employing a cycle‐sequencing strategy coupled with advanced analysis software to rapidly detect β‐thalassemia mutations in Israeli patients. This method enabled rapid identification of eight different mutations in 10 patients, including two rare mutations, one of which has never been described in this geographic region. Our results show that automated fluorescence‐based DNA sequence analysis of amplified genomic DNA is a rapid and reliable method for detection of point mutations and small deletions or insertions in both heterozygous and homozygous states. This approach is particularly effective for a relatively small gene such as β‐globin, but it can also be used for rapid detection of mutations in large genes by first sequencing clusters of exons and intron/exon borders. © 1994 Wiley‐Liss, Inc.
Rapid improvement of coagulopathy by all‐trans retinoic acid in acute promyelocytic leukemia
Authors: Kawai Yohko , Watanabe Kiyoaki , Kizaki Masahiro , Murata Mitsuru , Kamata Tetsuji , Uchida Hideo , Moriki Takanori , Yokoyama Kenji , Tokuhira Michihide , Nakajima Hideaki , Handa Makoto , Ikeda Yasuo 
Published: February 2007

AbstractTreatment of acute promyelocytic leukemia (APL) patients with all‐trans retinoic acid (ATRA) was associated with rapid improvement in hemostatic markers. We made serial analyses of various hemostatic parameters in seven newly diagnosed APL patients. In all patients at diagnosis, plasma fibrinogen/fibrin degradation product (fragment‐E), cross‐linked fibrin degradation product (D‐dimer fragment), thrombin‐antithrombin III complex and plasmin‐α2‐plasmin inhibitor complex were elevated, indicating the presence of disseminated intravascular coagulation (DIC). Antithrombin III (A TIII) levels were normal in all patients except for the patient with congenital ATIII deficiency. In four patients subsequently treated with ATRA without anticoagulant therapy, these hemostatic markers returned to near‐normal levels by day 7 of treatment, indicating that DIC was essentially resolved. By contrast, in three patients who received conventional chemotherapy with a continuous low‐dose heparin, improvement of coagulopathy was slower than in patients treated with ATRA. These results suggest that ATRA therapy exerts the rapid improvement in abnormal hemostatic markers in APL patients without any anticoagulant therapies, by inducing differentiation of leukemic cells and, in turns no massive release of procoagulant or fibrinolytic substances from these cells. © 1994 Wiley‐Liss, Inc.
Congenital coagulopathies and pregnancy: Report of four pregnancies in a factor X‐deficient woman
Authors: Kumar Manjusha , Mehta Paulette 
Published: February 2007

AbstractPregnancy in women with congenital coagulation factor deficiencies has been associated with adverse fetal outcomes. Recurrent spontaneous abortions, placental abruptions, and premature births are reported, the exact reasons for which are not clear, and management of such patients continues to be a challenge. We reviewed the outcome of four pregnancies in a patient with factor X deficiency, and looked at the effect of factor replacement therapy on pregnancy. Her first two pregnancies resulted in the birth of extremely premature babies at 21 and 25 weeks of gestation, both of which died in the neonatal period. The patient was treated with fresh frozen plasma for acute bleeding episodes during these pregnancies. In addition during her second conception she was given factor IX complex [Konyne] prophylactically, but only in the latter half of her pregnancy. During her next two pregnancies she was treated early on during pregnancy, with prophylactic replacement of factor X. She delivered healthy babies at 34 and 32 weeks of gestation, and they are both doing well. We therefore suggest possible mechanisms by which aggressive prophylactic factor support in a female with severe congenital coagulopathy, may improve on fetal outcome. © 1994 Wiley‐Liss, Inc.
Analysis of p53 gene mutations in acute myeloid leukemia
Authors: Trecca Dino , Longo Letizia , Biondi Andrea , Cro Lilla , Calori Rossella , Grignani Fausto , Maiolo Anna Teresa , Pelicci Pier Giuseppe , Neri Antonino 
Published: February 2007

AbstractWe have previously reported the absence of mutations within exons 5–9 of the p53 gene in a panel of 30 cases of acute promyelocytic leukemia (APL), which represent the M3 FAB type of acute myeloid leukemia (AML). In the present report, we extend our analysis of p53 gene mutations to 70 cases of AML representative of the other FAB types of the disease, including M1 (16 cases), M2 (20 cases), M4 (17 cases), M5 (12 cases), and M6 (5 cases). DNAs were analyzed for p53 gene mutations in exons 5 to 9 by polymerase chain reaction (PCR), single‐strand conformation polymorphism (SSCP), and direct sequencing of PCR‐ amplified products. Mutant p53 alleles were detected in 5 of 70 cases; 1 case in exon 5, 2 cases in exon 6, and 2 cases in exon 7. The alterations of the p53 gene were represented by point mutation leading to an amino acid substitution in four cases, and deletion in the remaining case. In four of the five cases, direct sequencing indicated the loss of the normal p53 allele; in the remaining case, two mutations were detected, presumably involving both p53 alleles. Three cases showed mutations at diagnosis; in the remaining two, the mutations were observed in clinical relapse but not at diagnosis. Our results confirm the relatively low incidence of p53 mutations in AML and further support the evidence that p53 plays a role in leukemogenesis through a recessive mechanism (two‐hit model) of inactivation of tumor suppressor activity. © 1994 Wiley‐Liss, Inc.
Cefotetan‐induced hemolytic anemia causing severe hypophosphatemia
Authors: Mohammed Suneel , Knoll Sandra , Van Amburg Albert , Mennes Paul A. 
Published: February 2007

AbstractPhosphorus is a major component of proteins, phospholipids, and nucleotides. The increased uptake of phosphorus by cells during erythropoiesis can result in severe hypophosphatemia. A case of severe hypophosphatemia due to accelerated erythropoiesis in response to Cefotetan‐induced hemolytic anemia is described. The hypophosphatemia seen during hemolysis may be the result, rather than the cause, of the hemolysis. © 1994 Wiley‐Liss, Inc.
Concurrent RhGM‐CSF does not offset myelosuppression from intensive chemotherapy: Randomized placebo‐controlled study in childhood acute lymphoblastic leukemia
Authors: Calderwood Stan , Romeyer Françoise , Blanchette Victor , Chan Helen , Doyle John , Greenberg Mark , Lorenzana Adonis , Malkin David , Saunders Fred , Weitzman Sheila , Zipursky Alvin , Freedman Melvin H. 
Published: February 2007

AbstractTo determine whether recombinant human granulocyte‐macrophage colony‐stimulating factor (rhGM‐CSF) can offset the myelosuppressive effects of intensive chemotherapy, we carried out a double‐blind placebo‐controlled trial in which 40 patients with acute lympho‐blastic leukemia (ALL) were randomized into two groups of 20 each. One group received rhGM‐CSF (5.5 μg/kg SC) coadministered with chemotherapy and the other, placebo coadministered with chemotherapy from day 5 to day 11 and from day 19 to day 25 of the 28‐day intensification phase of our institutional high‐risk protocol for childhood ALL. The results indicate that, at the dose and schedule used, rhGM‐CSF did not prevent neutrope‐nia or shorten the number of days required to complete this phase of therapy. In addition, the treated and placebo groups showed no significant difference in absolute neutrophil counts, number of days with neutropenia, number of days with fever, number of days spent in hospital, or number of days on antibiotics during the 28‐day study period. There was also no difference between the two groups in the number, type, or severity of Infectious episodes. Two of 20 patients in the treatment group have relapsed, whereas none of the patients in the placebo group has yet relapsed (follow‐up: 3–37 months), but these events were not statistically significant We conclude that treatment with rhGM‐CSF at the dose and schedule employed is not clinically beneficial. © 1994 Wiley‐Liss, Inc.
Serum lactate dehydrogenase and platelet count predict survival in thrombotic thrombocytopenic purpura
Authors: Patton Jeffrey F. , Manning Kenneth R. , Case Douglas , Owen John 
Published: February 2007

AbstractA significant number (some 20%) of patients with thrombotic thrombocytopenic purpura do not respond to standard therapy and die. We reasoned that early identification of those who are likely to fail standard therapy would allow the rational introduction of other treatment modalities. To this end we prospectively evaluated 27 consecutive patients, examining serum LDH levels and platelet counts as markers of disease activity and as predictors of outcome. All patients were treated, according to a written protocol, with high volume plasma exchange (35 ml/kg), prednisone, aspirin, and persantine. Twenty‐one of the 27 patients (78%) are alive following therapy. Initial LDH and platelet values did not distinguish between the survivors and nonsurvivors. However, by day 3 of therapy both LDH levels and platelet counts differed significantly between the two groups. Mean day 3 LDH level for survivors was 364 units/L, and for nonsurvivors, 891 units/L (P < 0.005). Mean day 3 platelet count for survivors was 119,000/μL, and for nonsurvivors, 46,000/μL (P < 0.005). Receiver Operator Characteristic curves were constructed and assessed by calculating the area under the curve. This analysis showed that LDH is able to discriminate survivorship one day earlier than platelet count. Both LDH level and platelet count are excellent predictors of survival, under standard therapy, after 3 days of treatment. Early identification of those at greatest risk will facilitate the early institution and evaluation of alternative methods of treatment, such as splenectomy, intravenous Ig, or Vincristine. © 1994 Wiley‐Liss, Inc.
Results of secondary prophylaxis in children with severe hemophilia
Authors: Manco‐Johnson Marilyn J. , Nuss Rachelle , Geraghty Susan , Funk Sharon , Kilcoyne Ray 
Published: February 2007

AbstractIn this study, 13 children with severe hemophilia were given routine replacement infusions of factor VIII or IX to treat arthropathy. The children who had a mean age of 6.9 years (range 2.0–12.5) at initiation of prophylaxis had experienced an average of 43 acute hemorrhages (range 8–127) in the year prior to prophylaxis, of which a mean of 24 (range 5–46) were into joints. Therapy was begun in five children, using factor VIII concentrate at 20 U/kg three times a week, and one boy received factor IX concentrate 40 U/kg twice a week. This dose schedule was inadequate for three factor VIII‐deficient boys and for the one factor IX‐deficient boy. Two of three factor VIII‐deficient boys responded to an increase to 30 U/kg prior to the 3‐day interval. The dose frequency was increased to three times a week for the factor IX‐deficient boy, but he continued to bleed and was taken to synovectomy. One of the original five factor VIII‐deficient boys plus seven other factor VIII‐deficient boys were begun on factor VIII 20 U/kg every other day; 3 boys ceased bleeding. Trough factor VIII levels were measured 24 hr after an infusion in the five boys who continued to bleed. Factor VIII dosage was adjusted to achieve a trough level of >1%; 4 responded to an increase in the dose of factor VIII; 1 had an adequate trough but, due to compliance issues, was taken to synovectomy. Serial clinical and radiographic assessments determined stabilization of joint disease in more than one‐half of the boys. No child showed reversal of abnormal radiographic findings. Institution of aggressive factor VIII and IX concentrate in children with established hemophilic arthropathy does not reverse joint disease but may alter the clinical course of hemophilia. Future studies to compare this intervention with primary prophylaxis instituted prior to the onset of recurrent joint hemorrhage are warranted. © 1994 Wiley‐Liss, Inc.
Characterization of apocytochrome C binding to human erythrocytes
Authors: Krishnan Gomathi , MacGregor Roderick D. , Shohet Stephen B. , Hunt C. Anthony 
Published: February 2007

AbstractThe binding of 125I‐labeled apocytochrome c to human erythrocytes was determined for free apocytochrome c concentrations at 10−10‐10−6 M. At about 2 × 10−9 M, maximum cell 22°C have three classes of apocytochrome c binding sites: one high‐affinity noncooperative site (n1 = 728 per cell, Kd1 = 1.5 × 10−9 M) and two positively cooperative sites (n2 = 3.7 × 104 per cell, Kd2 = 1.2 × 10−7 M, α2 = 2.0, and n3 = 2.5 × 105 per cell, Kd3 = 7.1 × 10−7 M, α3 = 12). Erythrocytes at 37°C, and erythrocyte ghosts at 22°C, also have three classes of apocytochrome c binding sites, and most sites are positively cooperative. © 1994 Wiley‐Liss, Inc.
Optimal blood stem cell mobilization using 10 μg/kg granulocyte colony‐stimulating factor (G‐CSF) alone for high‐dose melphalan intensification in multiple myeloma: An intrapatient controlled study
Authors: Feremans W. , Le Moine F. , Ravoet C. , Lambermont M. , Bastin G. , Delville J. P. , Pradier O. , Dupont E. , Capel P. 
Published: February 2007

AbstractA recent randomized multicentric French study has shown that intensification with stem cell rescue improves the response rate and progression‐free survival in multiple myeloma. Transplantation with primed peripheral blood stem cells (PBSC) displays a faster hematological recovery, especially for platelets, as compared with a bone marrow stem cell graft. In multiple myeloma, the optimal mobilization method for PBSC is unknown. The present study compares mobilization with cyclophosphamide 4 g/m2 + G‐CSF 5 μg/kg versus G‐CSF 5 μg/kg alone versus G‐CSF 10 μg/kg alone in two cases of multiple myeloma, using an intrapatient controlled evaluation of the amount of CD34‐positive cells obtained during each leukapheresis. In both cases, the highest CD34‐positive cells yield was obtained with G‐CSF at 10 μg/kg. Despite the low number of cases, this method, devoid of life‐threatening toxicity, might be of greatest interest in multiple myeloma. © 1994 Wiley‐Liss, Inc.
Anthracycline‐based therapy of de novo acute myeloid leukemia in adults: Failure of first‐cyde cytoreduction to predict second‐cycle outcome
Authors: Hammerschmidt Dale E. , Crea Mary T. Wild 
Published: February 2007

AbstractDuring 1971–1988, 194 adults with de novo acute myeloid leukemia (AML) received initial therapy at the University of Minnesota with an anthracycline‐based regimen. Seventy‐two of the 194 required further chemotherapy and received a second cycle of the same or similar therapy; 63 of these 72 were evaluable.For each marrow, a tumor burden index (TBI) was calculated, as the product of the marrow cellularity and the proportion of malignant cells. For each patient, the decrement in TBI between the initial and day ≈14 marrows was recorded. Patients who achieved second‐cycle CR were comparable to those who did not in general descriptors; there was no difference between second‐cycle CR achievers and nonachievers in the cytoreduction efleeted by the Initial cycle of therapy (74.9% ± 4.5% [σ] versus 71.9% = 5.9%).We then stratified patients according to the first‐cycle cytoreduction, asking if we could find a level that was reliably predictive of increased or decreased likelihood of achieving CR with cycle 2. We could not, despite testing at many centite cuts. Patients achieving a very “poor” degree of cytoreduction In cycle 1 were as likely to achieve CR with cycle 2 as were patients having a very “good” initial cytoreduction.We conclude that (1) first‐cycle response is not a useful predictor of second‐cycle outcome in anthracycline‐based therapy of de novo adult AML; and (2) a “poor” response to cycle 1 does not therefore a priori indicate a change to a different regimen for cycle 2. © 1994 Wiley‐Liss, Inc.
Effect of desferrioxamine and hydroxypyridones on hemopoietic progenitors and neuroectodermal tumor cells
Authors: Timeus Fabio , Valle Paola , Crescenzio Nicoletta , Ruggieri Luciano , Rosso Paolo , Pagliardi Giovanni Luca , di Montezemolo Luca Cordero , Gabutti Vilma , Ramenghi Ugo 
Published: February 2007

AbstractThe iron chelator desferrioxamine (DFO) has been shown to inhibit the proliferation of hemopoietic progenitors and several tumor cell lines. We have compared the in viro hemopoietic inhibitory effect of desferrioxamine (DFO) and hydroxypyridones (HPOs) on hemopoietic progenitors and two human neuroectodermal (NE) tumor cell lines, NB 100 and SKNMC. Both DFO and HPOs showed a direct dose‐related inhibitory effect on BFU‐E and CFU‐GM obtained from purified human non‐T MNAC (T‐Iymphocyte‐depleted nonadherent mononuclear cells) and CD34+ cells. DFO and HPOs displayed both an inhibitory and a cytotoxic effect on NE cell lines. We calculated the ratio between NE cell and hemopoietic cell growth inhibition for a range of concentrations of chelators. DFO showed the most satisfactory ratio. This suggests that DFO is still the most preferable chelating agent for the treatment of neuroblastoma, since it combines the highest antineuroblastoma effect with the lowest hematopoietic toxicity. © 1994 Wiley‐Liss, Inc.
Capacity of the store‐regulator in maintaining iron balance
Authors: Sayers Merlyn H. , English Genia , Finch Clement 
Published: February 2007

AbstractThere is evidence that iron stores alter iron absorption to meet body iron needs. In this study, quantitative aspects of this regulation of iron balance are examined. Two male subjects, one with low and one with average iron stores, were given additional dietary iron over 500 days. Changes in iron stores were monitored by plasma ferritin measurements, and the ferritin estimate of stores was validated at the end of the study by bleeding to the point of iron deficiency. The subject with low iron stores increased his ferritin by 39 μg/L or 0.8 mg/day, whereas the subject with average iron stores had no significant change. It is concluded that the mechanism by which stores regulate food iron absorption has a capacity of about 1 mg/day, sufficient to meet usual physiological needs, with the exception of pregnancy, as well as the ability to resist increase in stores above normal despite an iron rich diet. © 1994 Wiley‐Liss, Inc.
Compound heterozygosity for two α‐globin gene defects, Hb taybe (α1; 38 or 39 minus thr) and a poly a mutation (α2; AATAAA → AATAAG), results in a severe hemolytic anemia
Authors: Pobedimskaya D. D. , Molchanova T. P. , Streichman S. , Huisman T. H. J. 
Published: February 2007

AbstractWe have identified two α‐globin gene variations in an Arabian male with severe hemolytic disease through sequencing of amplified DNA of his α2‐ and α1‐globin genes. One of the abnormalities involves a CAC (ACC or CCA) deletion between codons 36 and 41 of the α1‐globin gene. This leads to the synthesis of an abnormal α chain with one instead of two threonine residues at positions 38–39 and to the formation of the unstable Hb Taybe. The second variation is a mutation located in the poly A site of the α2‐globin gene (AATAAA → AATAAG) which is common among Arabian people. Family studies have shown that the two variations are located on opposite chromosomes. The hemolytic disease in this man, resembling Hb H disease, is likely the result of a severe downregulation of both α‐globin genes on the chromosome with the α2 poly A mutation, and the instability of the α‐Taybe chain being the product of an α 1‐globin gene; this leaves only one α2‐globin gene normally active. © 1994 Wiley‐Liss, Inc.
Molecular characterisation of red cell glucose‐6‐phosphate dehydrogenase deficiency in Singapore Chinese
Authors: Saha S. , Saha N. , Tay J. S. H. , Jeyaseelan K. , Basair J. B. , Chew S. E. 
Published: February 2007

AbstractSixty‐two G6PD deficient Chinese males have been investigated for the presence of seven mutations of the coding region of the G6PD gene by natural and artifically created amplified restriction sites. The results show that the G to T substitution at nucleotide (nt) 1376 and G to A substitution at nt 1388 represent 24% and 21% of G6PD deficiency, respectively, in the Singapore Chinese; 37% of the sample could not be characterised. The remaining samples were identified as follows: 10% C→T at nt 563, 5% A→G at nt 95, and 3% C→T at nt 1024. The G to A substitution (nt 487) and the substitution A→G (nt 493) were not present in this sample. None of the subjects with the Mediterranean mutation (563 C→T) had the silent mutation at 1311 (C→T). This study confirms the extreme molecular heterogeneity of the G6PD gene in the Chinese. © 1994 Wiley‐Liss, Inc.