bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractIn 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

AbstractA 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

AbstractContinuous 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

AbstractThree 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

AbstractTwenty‐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

AbstractSerologic 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

AbstractIncreased 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

AbstractThe 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

AbstractA 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

AbstractLeg 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

AbstractThe 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

AbstractThe 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

AbstractA 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

AbstractSkin 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

AbstractThe 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

AbstractOver‐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

AbstractA 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

AbstractAnticardiolipin 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

AbstractA 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.