bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated soluble CD4 levels in the cerebrospinal fluid in patients with adult T‐cell leukemia
Authors: Uozumi Kimiharu , Hanada Shuichi , Ishitsuka Kenji , Ohno Nobuhito , Otsuka Maki , Shimotakahara Shigemi , Nakahara Katsushi , Takeshita Taketsugu , Chyuman Yoshiko , Kuwazuru Yasuo , Makino Torahiko , Saito Takeshi , Ishibashi Kazuaki , Iwahashi Masahito , Utsunomiya Atae , Arima Terukatsu
Published: February 2007

Levels of the soluble form of the leukocyte surface antigen CD4 (sCD4) were measured by enzyme linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of patients with adult T‐cell leukemia (ATL) and other malignant and non‐malignant diseases. All patients with ATL and meningeal infiltration had markedly elevated levels of sCD4 in the CSF (53.7 ± 34.9 U/ml). ATL patients without CSF pleocytosis often had elevated levels of sCD4 (15.1 ± 9.2 U/ml). Non‐ATL patients with CSF pleocytosis had elevated levels of sCD4 (23.3 ± 12.2 U/ml) and those without CSF pleocytosis also showed elevation of sCD4 levels (16.8 ± 9.3 U/ml). However, the mean levels of sCD4 in CSF from these patients were significantly lower than ATL patients with meningeal infiltration. Soluble CD4 in the CSF from healthy volunteers were below the detectable limit. We conclude that meningeal infiltration of CD4(+) ATL cells is strongly associated with elevated sCD4 levels in CSF, and some part of sCD4 in CSF may be originated from the native cells in the CNS as a response of inflammatory stimulations. Therefore, measurement of sCD4 may be useful in the diagnosis of meningeal infiltration and/or meningeal irritation in patients with ATL. © 1994 Wiley‐Liss, Inc.
Fetal hemoglobin synthesis in sickle cell anemia: Some molecular considerations
Authors: Bhaumik Kabita
Published: February 2007

An ability to maintain high levels of fetal hemoglobin (Hb F) has been associated with the amelioration of the clinical severity of the sickle cell disease (SS). Clinical efforts to increase the Hb F level of the patients have, however, yielded variable therapeutic response. In an attempt to further elucidate the underlying molecular basis, in vitro Hb F synthesis was studied in erythroid progenitor (BFU‐E) cells obtained from SS patients and their heterozygous (AS) relatives with varying genetic backgrounds. This allows us to study the Hb F biosynthesis pattern uncomplicated by the influence of the preferential survival of “F cells” In vivo. The Hb F levels and the relative concentrations of its constituent gamma globin chains, Gγ and Aγ, were assayed using the reversed phase HPLC method. A percentage increase in the fetal hemoglobin content was observed in the lysates of the erythroid progenitor cells relative to the circulating peripheral blood erythrocyte values in SS patients and their AS relatives with different βs haplotypes reflecting the intrinsic capacity of fetal hemoglobin synthesis in these subjects. No such increase was observed in the patient with the Mor haplotype. Furthermore, the Hb F synthesized in the BFU‐E colonies was more of the adult type, as evidenced by the decrease in the percent Gγlevel relative to the corresponding peripheral blood values of the subjects in all the haplotype groups studied. The Mor haplotype was again an exception, synthesizing fetal hemoglobin more of the fetal type. © 1994 Wiley‐Liss, Inc.
Genetic linkage studies in antithrombin‐deficient kindreds using a highly polymorphic trinucleotide short tandem repeat (str) within the human antithrombin gene
Authors: Ni H. , Waye J. S. , Sheffield W. P. , Eng B. , Blajchman M. A.
Published: February 2007

PCR amplification and analysis of short tandem repeats (STR) have provided a useful tool for genetic linkage studies and for the diagnosis of genetic disorders. We have recently identified a novel trinucleotide STR, (ATT) (TAA), in the fifth intron of the human antithrombin gene (AT3) located on chromosome 1q23. PCR amplification, cloning, and sequence analysis revealed this AT3‐STR to be highly polymorphic with repeat units ranging in size from (ATT)5 to (ATT)18 Ten distinct alleles were found in 81 unrelated Caucasian individuals (162 alleles) with an observed heterozygosity of 81%. Genetic linkage studies using the AT3‐STR in two previously described antithrombin (AT)‐deficient kindreds, AT‐Hamilton (Ala 382 Thr) and AT‐Amiens (Arg 47 Cys), demonstrate, in a given kindred, that a specific AT3‐STR polymorphism is strongly associated with a particular AT mutation. Thus, this highly polymorphic AT3‐STR should be very useful in performing linkage studies in AT‐deficient kindreds as well as in investigating other chromosome 1‐related genetic disorders. © 1994 Wiley‐Liss, Inc.
Increased binding of SP1 to the γ‐globin gene promoter upon site‐specific cytosine methylation
Authors: Sengupta Pritam K. , Lavelle Donald , Desimone Joseph
Published: February 2007

We have studied the effect of site‐specific cytosine methylation on the binding of nuclear proteins to the γ‐globin promoter region from −71 to −34. This sequence was recently shown to contain a stage selector element responsible for increased transcription from the γ compared to the β promoter when both are linked to Locus Control Region enhancer sequences. We observed that Sp1 binding to this sequence is increased upon site‐specific cytosine methylation, such that only methylation of the cytosine in the −50 CpG dinucleotide effects Sp1 binding. Methylation of the distal C of the Hpall site has no effect. The possible functional role of Sp1 as a repressor of γ‐globin synthesis is discussed. © 1994 Wiley‐Liss, Inc.
Reversal of nephrotic syndrome due to reactive amyloidosis (AA‐type) after excision of localized Castleman's disease
Authors: Perfetti Vittorio , Bellotti Vittorio , Maggi Anna , Arbustini Eloisa , De Benedetti Fabrizio , Paulli Marco , Marinone Maria Gabriella , Merlini Giampaolo
Published: February 2007

The patient (TAL), a chronic asymptomatic HBV carrier with HBsAg‐anti‐HBsAg circulating immune complexes, was admitted to our hospital because of a nephrotic syndrome due to renal amyloidosis. There was no family history of hereditary amyloidosis. Recurrent arthralgias, asthenia, and weight loss were the prominent clinical features. Laboratory test results showing that severe chronic inflammatory activity had been present for 6 years. Interleukin‐6 (IL‐6) serum concentration was 10 times normal and C‐reactive protein was 1.9 mg/ml. A complex immunological picture was also present (immune complex formation, exuberant B‐cell reactivity, and decrease in the number of CD4 T cells). A localized form of Castleman's disease (CD) (plasma‐cell type) was diagnosed by surgical excision of a giant axillary lymph node. AA amyloid was present in the blood vessels. Within 60 days after excision of the mass, the systemic symptoms subsided, laboratory signs of inflammatory activity disappeared and IL‐6 serum concentration returned to normal, thus establishing a causal relationship between the localized Castleman's disease, elevated IL‐6 concentration and the chronic inflammation responsible for AA amyloidosis. At 10 months of follow‐up, the nephrotic syndrome has reversed, kidney function has slowly ameliorated, and the patient has gained 12 kg. Abdominal fat aspirates drawn to search for amyloid, positive before surgery, were subsequently negative. The latter finding, and the remission of the nephrotic syndrome, provided strong evidence for regression of the amyloid deposits. However, the HBsAg‐anti‐HBsAg immune complexes and depression of T‐helper cell activity persist. This immunological derangement is therefore not a consequence of CD. Chronic stimulation of the immune system due to the patient's inability to eliminate HBV, in the contest of perturbed immunity, may have favored the genesis of the lymphadenopathy. © 1994 Wiley‐Liss, Inc.
Moderate hemophilia B leyden: Identification by polymerase chain reaction, sequencing, and oligomer restriction
Authors: Coyle Thomas E. , Spicer Timothy , Michalovic Doris , Poiesz Bernard J.
Published: February 2007

Hemophilia B Leyden is a rare form of congenital factor IX deficiency which is characterized by severe factor IX deficiency at birth, which ameliorates after puberty. It is caused by mutations in the factor IX gene promoter region and the postpubertal amelioration is thought to be mediated by the action of testosterone on an androgen response element located in the promoter region. Three kindreds have been previously reported with a milder form of hemophilia B Leyden, associated with a guanine to adenine transition at nucleotide position −6 of the promoter region. We now report a fourth kindred with this mutation. The proband was a newborn with a factor IX level of 2.5%, his 12‐year‐old half‐brother had a level of 28%, and his mother's 56‐year‐old maternal cousin had a level of 60%. A G to A transition at nucleotide −6 of the promoter region was demonstrated by cloning and sequencing polymerase chain reaction products from the half brother, and the mother was demonstrated to be a carrier. The mutation eliminates a Taql. restriction endonuclease site normally present in the wild type promoter, and the mother's cousin was demonstrated to carry the mutation by the absence of digestion with Taql. The identification of hemophilia B Leyden with this specific mutation has practical importance to the clinical management because of its unique natural history and significantly better prognosis than classical hemophilia B. © 1994 Wiley‐Liss, Inc.
Plasma protein c activity is enhanced by arsenic but inhibited by fluorescent humic acid associated with blackfoot disease
Authors: Yang Hsin‐Ling , Tu Shu‐Chin , Lu Fung‐Jou , Chiu Hui‐Chong
Published: February 2007

Blackfoot disease is a peripheral vascular disease causally related to the fluorescent humic acid found in the drinking water of endemic areas in Taiwan. We compared the effects of humic acid (HA) purified from the well water of Blackfoot disease endemic areas with the effects of commercial humic acid (Aldrich) as well as trivalent arsenic (As2O3) on protein C activity, which plays an important role in regulation of blood coagulation and fibrinolysis. Humic acid, either purified from drinking water or obtained commercially, dose‐dependently inhibited both activated protein C activity and the activation of protein C induced by Protac, a snake venom‐derived protein C activator. In contrast to humic acid, arsenic oxide dose‐dependently enhanced both activated protein C activity and the Protac‐stimulated activation of protein C. In the presence of humic acid the enhancement effect of arsenic oxide was completely abolished, resulting in concentration‐dependent inhibition of protein C activity. Therefore, the results of this study indicate that humic acid is a potent protein C inhibitor even in the presence of arsenic, which enhances the protein C activity. Since protein C is a potent anticoagulant and profibrinolytic agent, acquired defects of protein C induced by humic acid might cause a thrombophilic or hypercoagulable state. Whether this is one of the possible mechanisms of humic acid‐induced thrombotic disorders in Blackfoot disease needs to be further characterized. © 1994 Wiley‐Liss, Inc.
Soluble fibrin: A predictor for the development and outcome of multiple organ failure
Authors: Bredbacka Sixten , Blombäck Margareta , Wiman Björn
Published: February 2007

According to our hypothesis ICU patients with signs of early hypercoagulation should develop more organ system failures that result in higher mortality rates and longer treatment periods. Routine coagulation tests are unreliable for measuring early hypercoagulation. Methods: Soluble fibrin (SF), reflecting hypercoagulation, was assessed at an early stage in 101 ICU patients. A spectrophotometric method using chromogenic peptide substrates was employed. The patients were divided into four groups, depending on the patient's highest level of SF within the first week after admission: Group I (21 patients), SF < 15 nmol/L (reference level); Group II (27 patients), SF 15–29 nmol/L; Group III (26 patients), SF 30–50 nmol/L and Group IV (27 patients), SF > 50 nmol/L. The number of secondary failing organ systems and the ventilator time, ICU time and mortality rates were recorded. Results: There was a significant increase in the number of secondary failing organ systems (P < 0.0001) and a significantly increased mortality for the groups with higher SF (P − 0.01). There was a mean of 0.6, 1.3, 2.4, and 3.4 failing organs and a mortality of 14%, 22%, 30%, and 46% in the respective groups. The ventilator time and the ICU time were longest in Group III, but again shorter for Group IV (with the highest mortality). The mean ventilator times were 2.7, 6.4, 8.4, and 5.9 days and the mean ICU times were 4.1, 8.6, 10.3, and 7.3 days in the respective groups. Thirteen patients with SF > 100 nmol/L had a mean of 4.2 failing organ systems and an 85% mortality. Conclusion: Soluble fibrin, a marker of hypercoagulation, seems to predict organ system failure and outcome in ICU patients. © 1994 Wiley‐Liss, Inc.
Prognostic factors for therapeutic outcome of diffuse small non‐cleaved cell lymphoma in adults
Authors: Morrison Vicki A. , Frizzera Glauco , Arthur Diane C. , Ogle Kathleen M. , Hurd David D. , Bloomfield Clara D. , Peterson Bruce A.
Published: February 2007

Most reports of prognosis and therapy in diffuse small non‐cleaved cell lymphoma (DSNCL), an aggressive high‐grade non‐Hodgkin's lymphoma (NHL) which appears to be of two histopathologic subtypes, have included predominantly a pediatric population and very few adults. We studied 20 newly diagnosed, previously untreated adults with DSNCL. Three patients had Ann Arbor Stage I disease, five Stage II, and 12 Stage IV. Bone marrow involvement was present in seven of 20 (35%) patients; no patient had central nervous system involvement at diagnosis. Clonal chromosomal abnormalities were found on cytogenetic analysis of all 12 cases studied. Ten patients had specific recurring translocations, including t(8;14) (q23;q32) (five patients), t(14;18) (q32;q21) (four patients), and t(2;8) (p12;q24) (one patient). Induction chemotherapy with the COMP regimen (cyclophosphamide, vincristine, methotrexate, and prednisone) or a variant schedule of the same drugs resulted in complete remission for 13 patients (65%), and partial remission for 5 patients (25%). Clinical characteristics predictive of a favorable response to induction therapy included Stage I or II disease, a normal lactic dehydrogenase (LDH), and performance status (PS) of 0 or 1. Remission duration ranged from two to 125+ (median 37+) months. Survival ranged from one to 126+ (median 23) months; ten patients (50%) remain alive, nine with no active disease. Factors predictive of longer survival included achievement of a complete remission with induction therapy, a normal LDH, and PS 0 or 1. As in children with DSNCL, long‐term disease‐free survival may be achieved in adults with combination chemotherapy. © 1994 Wiley‐Liss, Inc.
Recombinant activated factor VII (rFVIIa) therapy for intracranial hemorrhage in hemophilia a patients with inhibitors
Authors: Schmidt M. L. , Gamerman S. , Smith H. E. , Scott J. P. , DiMichele D. M.
Published: February 2007

We report the use of recombinant VIIa (rFVIIa) in the treatment of five ICHs in two factor VIII‐deficient patients with inhibitors. In four of five ICHs, rFVIIa was the only factor replacement used at doses of 60–135μ/kg every 2–4 hr for 12–14 days. Hemostasis at the primary site of bleeding was achieved in all cases, and all patients survived with no permanent neurologic deficits. However, the patient who received the highest dose of rFVIIa during the first 4 days of therapy developed clinical symptoms consistent with a cerebral vascular accident of the brainstem characterized by acute onset of truncal ataxia and upward‐gaze nystagmus on day 8 of rFVIIa therapy. While receiving rFVIIa therapy for treatment of these five ICHs, four treatment courses were complicated by bleeding at sites other than the primary site, including two episodes of localized oozing at central line insertion sites, two episodes of hemarthrosis, and two episodes of epistaxis. Antifibrinolytic therapy with tranexamic acid was effective in two of these episodes. Laboratory evaluation revealed shortening of the PT, variable shortening without normalization of the APTT, peak factor VII activity levels 7–30‐fold higher than normal baseline values, and normal antithrombin III (ATIII) and β‐antiplasmin levels. In four of five ICHs, there was a 20–40% decrease in fibrinogen levels from baseline. The decrease in fibrinogen was accompanied by an increase in fibrin degradation products in 3/5 episodes and a 15–35% decrease in plasminogen activity levels in 2/5 episodes. Tissue factor pathway inhibitor (TFPI) levels remained stable and in the normal range. Although rFVIIa is an effective new therapy for the treatment of ICH in hemophilia patients with inhibitors, its optimal use with respect to safety and efficacy requires further clinical study. © 1994 Wiley‐Liss, Inc.
Transplantation of allogeneic peripheral blood stem cells after myeloablative treatment of a patient in blastic crisis of chronic myelocytic leukemia
Authors: Sasaki Atsuko , Tsukaguchi Machiko , Hirai Manabu , Ohira Hidehiro , Nakao Yoshitaka , Yamane Takahisa , Park Keunsik , Im Taesung , Tatsumi Noriyuki
Published: February 2007

A 48‐year‐old man in blastic crisis of chronic myelocytic leukemia received a transplant of allogeneic peripheral blood stem cells. The donor was his HLA‐identical sister, who refused to donate bone marrow cells, but agreed to donate peripheral blood stem cells. The patient received standard transplant conditioning with cyclophosphamide (120 mg/ kg) and busulfan (16 mg/kg). Peripheral blood stem cells were mobilized with granulocyte colony stimulating factor and collected by apheresis. After transplantation, the white blood cell count and the result of microscopic analysis of the bone marrow became normal, and the leukocyte karyotype became 46XX. DNA fingerprinting showed complete chimerism. Graft‐versus‐host disease was suppressed with cyclosporine and methyl‐prednisolone. The patient died of recurrence of leukemia on day 102+. © 1994 Wiley‐Liss, Inc.
Comparison of initial lymphoma staging using computed tomography (CT) and magnetic resonance (MR) imaging
Authors: Hoane B. Richard , Shields Anthony F. , Porter Bruce A. , Borrow James W.
Published: February 2007

While MR is known to be superior to other imaging methods for detecting marrow involvement by lymphoma, MR is also capable of detecting abnormal lymph nodes. Our objective was to determine whether MR employing short Tl inversion recovery (STIR) was comparable to CT in the initial staging of 23 patients with Hodgkin's disease (12 patients) and non‐Hodgkin's lymphoma (11 patients). MR images of chest, abdomen, pelvis, and femoral marrow were obtained using the STIR and T1‐weighted spin‐echo (T1‐SE) techniques, employing a protocol initially designed for marrow assessment. In all cases, CT‐detected adenopathy was also found by MR. Four patients had marrow involvement by MR, undetected by CT. We conclude that MR and CT may be equivalent imaging modalities in the detection of nodal involvement, and that MR has an advantage in its ability to diagnose marrow involvement. Given the high frequency of focal marrow abnormalities detected by MR in patients with Hodgkin's disease and high‐grade non‐Hodgkin's lymphoma, MR may be the preferred staging modality for these patients. © 1994 Wiley‐Liss, Inc.
Rearrangement and expression of MDM2 oncogene in chronic lymphocytic leukemia
Authors: Huang Yao Qi , Raphael Bruce , Buchbinder Aby , Li Jian Jun , Zhang Wei Gue , Friedman‐Kien Alvin E.
Published: February 2007

Since trisomy 12 is the most common chromosome abnormality found in CLL and MDM2 has been mapped to this chromosome, we examined the possible association of MDM2 in the pathogenesis of CLL. A rearrangement of the MDM2 gene was observed in 4 of 11 peripheral blood mononuclear cells (PBMC) from patients with CLL by Southern biot hybridization. Expression of MDM2 was detected in all of the CLL samples examined by Northern blot. However, neither gross amplification nor overexpression of the MDM2 gene was found in CLL. The data suggest that MDM2 may play a role in the pathogenesis of CLL and may help to explain how abnormalities of chromosome 12 are related to CLL. © 1994 Wiley‐Liss, Inc.
Antithrombotic effects of recombinant human soluble thrombomodulin (rhs‐TM) on arteriovenous shunt thrombosis in rats
Authors: Aoki Yoshikazu , Takei Ryoichi , Mohri Mitsunobu , Gonda Yasunori , Gomi Komakazu , Sugihara Taisuke , Kiyota Takao , Yamamoto Shuji , Ishida Torao , Maruyama Ikuro
Published: February 2007

We examined the antithrombotic effect of recombinant human soluble thrombomodulin (rhs‐TM) using an arteriovenous shunt thrombosis model and its influence on hemostasis in rats. Intravenous administration of rhs‐TM (0.5–4 mg/kg) significantly inhibited thrombus formation and prolonged ex vivo activated partial thromboplastin time (APTT) in a dose‐dependent manner. Thrombus formation was inhibited to the same extent in animals treated with heparin (25–200 U/kg) and in those treated with rhs‐TM (0.5–4 mg/kg), but heparin had a much stronger effect on prolonging APTT. In the hemorrhagic study using the rat template bleeding time method, rhs‐TM exhibited the prolongation of the bleeding time only at the highest effective dose (rhs‐TM; 4 mg/kg) of the thrombosis experiments. Thus, rhs‐TM exhibits the inhibitory effect on thrombus formation with less APTT prolongation in comparison with heparin and without significant pertubation of hemostasis. © 1994 Wiley‐Liss, Inc.
Serum vitamin B12 and transcobalamin levels in early HIV disease
Authors: Rule S. A. J. , Hooker M. , Costello C. , Luck W. , Hoffbrand A. V.
Published: February 2007

A cohort of asymptomatic human immunodeficiency virus (HIV) seropositive patients was followed over a 2 1/2‐year period, to establish changes in serum vitamin B12 (B12) concentrations. Serum B12, CD4 count, and clinical progression to acquired immunodeficiency syndrome (AIDS) or AIDS‐related complex (ARC) were measured. The unsaturated B12 binding capacities of the transcobalamins were also determined at the start of the study and compared to those from a homosexual HIV seronegative control group.

The geometric mean of serum B12 in 218 asymptomatic HIV seropositive patients was significantly lower than of a homosexual HIV seronegative control group (P = 0.02) and the unsaturated B12 binding capacities of transcobalamins I and II were significantly higher in the asymptomatic patients compared with the same control group (P < 0.03, P < 0.0001, respectively).

Fifty‐nine of the asymptomatic HIV seropositive patients were followed over a 2 1/2‐year period during which most had falling serum B12 levels (64%). Twelve patients progressed clinically to ARC or AIDS, of which nine had repeat serum B12 estimation prior to progression. All nine patients had or developed falling serum B12 levels without any evidence of an HIV‐related bowel disorder. All patients progressing had falling CD4 counts.

Subnormal serum B12 levels are common in HIV disease and occur at an early stage. B12 levels fall in most patients with time and may help predict those patients whose disease will progress the most rapidly. © 1994 Wiley‐Liss, Inc.
Gastrointestinal histoplasmosis presenting as hematochezia in human immunodeficiency virus‐infected hemophilic patients
Authors: Becherer Paul R. , Sokol‐Anderson Marcia , Joist J. Heinrich , Milligan Thomas
Published: February 2007

Two hemophiliacs infected with human immunodeficiency virus (HIV) presented with hematochezia secondary to gastrointestinal involvement with Histoplasmosis capsulatum. In one patient who was already receiving fluconazole, the diagnosis was obscured. Both patients responded to amphotericin B followed by intraconazole, with no recurrence of bleeding. © 1994 Wiley‐Liss, Inc.
Ultrastructure of fibrillar granules in human neutrophils
Authors: Takemori Nobuo , Hirai Katsuyuki , Onodera Ryuichi , Saito Nagahito , Miyokawa Naoyuki
Published: February 2007

Fibrillar granules (FGs) represent neutrophilic primary granules containing clustered filaments. We investigated neutrophils in the bone marrow obtained from 17 patients with chronic myeloproliferative disorders (CMPD) by electron microscopy. FG‐positive neutrophils were seen in 15 of the 17 CMPDs with varying frequencies. The diameter of FG‐filaments was 7–8 nm, showing that they corresponded to neither intermediate filaments nor actin filaments. © 1994 Wiley‐Liss, Inc.
HCG contamination of alglucerase: Clinical implications in low‐dose regimen
Authors: Cohen Yael , Elstein Deborah , Abrahamov Ayalah , Hirsch Harry , Zimran Ari
Published: February 2007

Alglucerase (Ceredase) is currently the treatment of choice for patients with symptomatic Gaucher disease. The contamination of this placental enzyme with human chorionic gonadotropin (hCG) has raised concern regarding possible endocrinological complications. We examined 32 patients treated with low‐dose alglucerase and 27 untreated patients as controls, and found no significant clinical differences between the two groups: no prepubertal children were affected, no menstrual irregularities were reported, and all hCG levels were well within normal range. Conversely, our finding of a statistically significant difference between the groups underscores the importance of initiating parallel studies of hCG contamination in patients receiving high‐dose protocol. © 1994 Wiley‐Liss, Inc.
Acute bone marrow toxicity and pancytopenia following exposure to lead chromate, xylene, and ethylbenzene in a degloving injury
Authors: Erickson Timothy , Amed Vasia , Leibach Steven J. , Bushnik Philip , Saxon Allen , Hryhorczuk Daniel O. , Knopse William H.
Published: February 2007

A case of unique acute bone marrow toxicity and pancytopenia following subcutaneous exposure to lead chromate, xylene, and ethylbenzene in a previously healthy patient is reported. The patient sustained an extensive degloving injury to his lower extremity. The wound was contaminated with traffic paint containing lead chromate pigment along with a large volume of xylene and ethylbenzene solvent. Consequences of the patient's clinical course and management of degloving injuries are discussed. © 1994 Wiley‐Liss, Inc.
Fibrinolytic pattern in recurrent spontaneous abortions: No relationship between hypofibrinolysis and anti‐phospholipid antibodies
Authors: Patrassi G. M. , Sartori M. T. , Ruffatti A. , Viero M. , Di Lenardo L. , Cazzanello D. , Ghirardello A. , Boeri G. , Saggiorato G. , Girolami A.
Published: February 2007

Patients with antiphospholipid antibodies may suffer from thrombotic events and recurrent spontaneous abortions. A defective fibrinolytic potential has been described in women with recurrent fetal losses. We investigated the prevalence of anticardiolipin antibodies and of various fibrinolytic abnormalities in 64 females with a history of at least two abortions of unknown origin. Anticardiolipin antibodies were present in the serum of 31 patients (48.4%). The overall prevalence of fibrinolytic disorders was 67.2% (43 cases) and resulted significantly higher than that of aCL positivity (P = 0.03). In most of cases the impaired fibrinolytic potential after venous occlusion test was due to increased PAI‐1 levels; only in a few instances a defective fibrinolytic response was due to reduced t‐PA release, a combined defect or an intrinsic fibrinolytic deficiency. After division of patients in two groups on the basis of the aCL presence, the distribution of different fibrinolytic defects was similar in aCL positive and negative women, suggesting the lack of correlation between hypofibrinolysis and aCL antibodies. Plasminogen abnormalities resulted compatible with congenital hypoplasminogenemia in two aCL negative women, whereas in four aCL positive patients they were suggestive for acquired dysplasminogenemia.

Our results indicate that patents with recurrent spontaneous abortions may present fibrinolytic disorders, which occur independently and more often than aCL positivity. An accurate investigation of the fibrinolytic potential, and, namely, of PAI‐1 levels, should be included in the study of females suffering from repeated fetal losses. © 1994 Wiley‐Liss, Inc.
PA‐IgG on platelet subpopulations of different buoyant densities: High levels on the low density population is an artifact
Authors: Rososhansky Sarah , Szymanski Irma O.
Published: February 2007

We isolated subpopulations of normal blood platelets from platelet rich plasma (PRP) and, in parallel, from platelet rich saline (PRS) on the basis of their buoyant densities. The MPV, being smallest in the lightest subpopulation, correlated significantly with platelet buoyant density (P < 0.002). In agreement with previous reports, we showed that the least dense platelet subpopulation, separated from PRP, had a high level of PA‐IgG (3,486 mol/plt). This value was significantly greater (P < 0.02) than PA‐IgG in the lightest subpopulation separated from PRS (693 mol/plt). We believe that the procedure of separating platelets from PRP artificially increased PA‐IgG in the least dense subpopulation. Our data showed that when Subpopulations were prepared from PRS, PA‐IgG correlated with platelet buoyant density (P < 0.002), and that the subpopulation with the highest density had the highest level of PA‐IgG. © 1994 Wiley‐Liss, Inc.
Copper deficiency‐induced anemia and neutropenia secondary to intestinal malabsorption
Authors: Hayton Bruce A. , Broome H. Elizabeth , Lilenbaum Rogerio C.
Published: February 2007

A patient with a history of partial gastrectomy presented with severe anemla, neutropenia, intestinal malabsorption, and was found to be severely copper‐deficient. The anemia and neutropenia corrected promptly with the administration of intravenous cupric chloride. This case suggests that partial gastrectomy with or without intestinal malabsorption can result in copper deficiency and should be considered in differential diagnosis of severe anemia and neutropenia. ©1995 Wiley‐Liss, Inc.
Significant and persistent improvement of thrombocytopenia after splenectomy in an adult with the wiskott‐aldrich syndrome and intra‐cerebral bleeding
Authors: Gaspoz Jean‐Michel , Waldvogel Francis , Cornu Pierre , Gugler Edouard , Dayer Jean‐Michel
Published: February 2007

The Wiskott‐Aldrich syndrome is an X‐linked inherited immunodeficiency disorder characterized by thrombocytopenia, recurrent infections and eczema. Its best management option is HLA‐ldentical bone marrow transplantation; when this is not feasible, splenectomy, followed by continuous prophylactic antibiotics, represents the alternative of choice.

The present case report relates the excellent outcome of an adult with the Wiskott‐Aldrich syndrome who suffered his first major complication of the disease at age 33 years, an intracerebral hemorrhage. Since an uneventfull splenectomy, thrombocytopenia has significantly improved, and he has remained free of infections for a follow‐up period of 3 years while being treated with prophylactic antibiotics. ©1995 Wiley‐Liss, Inc.
Design and validation of a bedside decision instrument to elicit a patient's preference concerning allogenic bone marrow transplantation in chronic myeloid leukemia
Authors: Sebban C. , Browman G. , Gafni A. , Norman G. , Levine M. , Assouline D. , Fiere D.
Published: February 2007

The objective of this study was to design and validate a bedside decision instrument to be used by patients with chronic myeloid leukemia and their physicians in deciding between the therapeutic alternatives of bone marrow transplantation and conservative management during the early phase of disease.

A decision board was constructed containing detailed scenarios associated with the treatment alternatives, together with estimates of survival probabilities at various periods of followup. The instrument was tested on 42 healthy hospital personnel and validated by measuring the extent to which systematic alterations in the scenarios with respect to toxicities and survival probabilities produced predicted shifts in treatment preferences. A subgroup of respondents was randomized to receive information through the decision board alone or a shorter and less informative version of the instrument, followed by the decision board. The direction and strength of stated preferences were compared, together with satisfaction for these preferences.

The direction and strength of preferences between bone marrow transplantation or conservative chemotherapy were influenced in a predictable way by changes in the toxicity and survival descriptions in the scenarios. Using the test‐retest method in 16 subjects, the stated preferences were found to be highly reliable (intraclass correlation coefficient, 0.87). The mean level of satisfaction with the stated preference, on a scale from not at all satisfied = 1 to very satisfied = 5, was higher for those exposed to the decision board (3.7, SD 1.06) compared with those presented with the short version (2.95, SD 0.67) (p < 0.01).

The results demonstrate the feasibility and acceptability of the instrument in healthy individuals. The preferences elicited by the instrument appear to be reliable and valid according to prespecified constructs of the relation between the information provided and the preferences predicted. These results support further testing of this approach in actual patients. © 1995 Wiley‐Liss, Inc.
Myelodysplastic syndrome treatment with danazol and cis‐retinoic acid
Authors: Letendre Louis , Levitt Ralph , Pierre Robert V. , Schroeder Georgene , Krook James A. , Mailliard James E. , Morton Roscoe F. , Tschetter Loren K.
Published: February 2007

We prospectively treated 46 patients with favorable myelodysplastic syndrome classified as refractory anemia (RA), refractory cytopenia (RC), or refractory anemia with ringed sideroblasts (RARS). These patients received one of two schedules of 13‐Cis‐Retinoic Acid (low dose 80 mg daily for 6 months vs. high dose 200 mg po daily for 3 months), or Danazol (800 mg po daily for 3 months), and were crossed over to the alternative drug in the absence of response or at progression.

Using strict criteria of response we found little objective evidence of activity for either compound. Only two minor responses were seen among 22 patients treated with low dose 13‐CRA, 1 response among 20 cases that received high dose 13‐CRA, and 1 partial response and 1 minor response to Danazol among 34 cases.

Neither 13‐Cis‐Retinoic Acid nor Danazol appear active enough in patients with favorable myelodysplastic syndrome to justify their use. © 1995 Wiley‐Liss, Inc.
Discrimination of Hb D Los Angeles (B121 Glu‐Gln) and Hb Beograd (B121 Glu‐Val) by Dual Restriction Enzyme Analysis
Authors: Akar N. , Özden A. , Akar E. , Cin S. , Arcasoy A.
Published: February 2007

Hb D Los Angeles (B121 Glu‐Gln) and Hb Beograd (B121 Glu‐Val) can be identified by different techniques. Here we describe a dual restriction enzyme digestion protocol (EcoR I G AATTC) and Tsp509 I (AATT) for the discrimination of these variants.
Expression pattern of CD45 RA/RO isoformic antigens in T‐lineage neoplasms
Authors: Kawano Seiji , Tatsumi Eiji , Yoneda Noriko , Tani Akemi , Nakamura Fumihiko
Published: February 2007

The expression of CD45 RA/RO antigen was investigated in neoplasms including cases expressing CD7 antigen as the sole pan‐T antigen (n = 8), T‐lineage acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL) at various stages of differentiation (n = 32), peripheral stage T‐lineage leukemia (n = 10) and adult T‐cell leukemia (ATL) (n = 14). The p56Ick gene expression was also investigated in selected cases.

The expression pattern of CD45 RA/RO antigen was defined as of RA, mixed, or RO type. All but one CD7+ CD5− CD2− case were of the RA type. The CD7+ CD5+ CD2− prothy‐mic stage included seven RA and one mixed type cases. One CD7+ CD5− CD2+ case was of the RA type, but the other was of the RO type. The CD7+ CD5+ CD2+ prothymic stage included three RA and four mixed type cases. All seven CD3− CD4+ CD8+ (double‐positive) thymic cases were of the RO type. The CD3+ CD4+ CD8+ (triple‐positive) stage included two RO and three mixed‐type cases. One CD3+ CD4+ CD8− late thymic case was of the mixed type. The peripheral stage cases included five RA, three RO, and two mixed type cases. All ATL cases were of the RO type. The expression of p56Ick gene in the prothymic stage was less marked than that in the thymic stage.

On the basis of these results, the following sequence of pattern of the CD45 RA/RO antigen expression along with T‐lineage differentiation was reconstructed: prothymic stage [RA and mixed type] → double‐positive thymic stage [RO type] → triple‐positive thymic stage [RO and mixed type] → peripheral stage [RA, mixed, and RO type]. While one RO‐type CD7+ CD5− CD2− and one RO‐type CD7+ CD5− CD2+ cases were not in accord with this sequence, the pattern of CD45 RA/RO antigen expression in most of T‐lineage neoplasms could be determined by the respective stage of differentiation. The poor expression of the p56Ick gene by the prothymic blasts compared with the thymic blasts may be related to the expression pattern of the CD45 RA/RO molecules, which exhibits phosphatase activity. The consistent RO‐type expression in the ATL cases may reflect the activated status of the neoplastic T cells due to the presence of the HTLV‐I gene. Alternatively, the target cells for HTLV‐I‐induced neoplastic transformation may possibly be of the RO type. © 1995 Willey‐Liss, Inc.
Application of interphase cytogenetics to monitor bone marrow transplants
Authors: Vrazas Vickie , Ooms Lisa M. , Rudduck Christina , Szer Jeffrey , Campbell Lynda J. , Garson O. Margaret
Published: February 2007

Chromosomal in situ hybridization (ISH) has extended the scope of cytogenetic analysis to nondividing cells by the use of chromosome‐specific probes detected by nonisotopic techniques. This provides a rapid and sensitive method for identifying chromosomes in interphase cells, and is useful in gauging engraftment following bone marrow transplantation, particularly when the number of cells obtained is minimal. We have performed ISH using a Y‐heterochromatin‐specific probe to monitor patients with malignant hematological disease who have received a sex‐mismatched transplant. The results have been compared with those obtained from concurrently performed standard cytogenetic analysis. Host cells were detected by interphase cytogenetics in all patients posttransplant, at times varying from 28‐1,825 days, whereas routine analysis detected host cells in only 4 patients, 3 of whom were found to be in relapse. The significance of the persistence of host cells is unknown, but it does not appear to indicate impending relapse. © 1995 Wiley‐Liss, Inc.
Essential thrombocythemia: A retrospective analysis of 39 cases
Authors: Kwong Y. L. , Liang R. H. S. , Chiu E. K. W. , Lie A. K. W. , Chan L. C. , Todd D. , Chan T. K.
Published: February 2007

Thirty‐nine Chinese patients presenting as essential thrombocythemia (ET) were analyzed retrospectively. The median age at presentation was 69 years and the M:F ratio was 1.35:1. At diagnosis, 33 cases (84%) were asymptomatic and the diagnosis was made incidentally, while 3 cases (8%) presented with small vessel, and 2 cases (5%) with large vessel, thrombosis. One patient (3%) presented with minor bleeding. The platelet count ranged from 0.9‐34 × 1012/1. Of 12 karyotypes done, 2 cases were abnormal, both showing the Philadelphia (Ph) chromosome. First‐line therapy was radiophosphorus (32P) in 3 cases, melphaian in 20 cases, and hydroxyurea in 12 cases; 4 cases did not receive specific therapy. During the follow‐up (mean = 4 years), no thrombotic or bleeding episodes were observed. One patient with the Ph chromosome underwent blastic transformation. These results indicate that bleeding and thrombosis occur significantly less in Chinese patients than in Western patients. The Ph chromosome appears to be a bad prognostic indicator. Because of the very low incidence of complications and good prognosis, the authors believe that cytoreductive therapy is best achieved by the use of hydroxyurea instead of alkylating agents or radiophorphours, as the latter agents are potentially leukemogenic. © 1995 Wiley‐Liss, Inc.
Myocardial infarction and thalassemia trait: An example of heterozygote advantage
Authors: Wang Cheng‐Hsu , Schilling Robert F.
Published: February 2007

This study was designed to test the hypothesis that thalassemia trait diminishes the likelihood of myocardial infarction. If the hypothesis is true the prevalence of thalassemia trait should be less in myocardial infarct patients than in a control population. Blood counts and blood chemistry data from 500 men in Taiwan with a discharge diagnosis of myocardial infarction were recorded, and similar data were gathered on 500 men admitted to the same hospital for a routine check‐up. Thalassemia trait was diagnosed via a discriminant function applied to the red blood cell count and indices. The study was done in a large modern hospital in Taipei; 14 of the 500 infarct patients and 33 of the 500 non‐infarct subjects had thalassemia trait as defined here. The prevalence of thalassemia trait in myocardial infarct patients is significantly less than in the control subjects. This case control study supports the hypothesis that thalassemia trait lessens the risk of myocardial infarction. © 193s Wiley‐Liss, Inc.
Inhibitory activity of anti‐β2‐glycoprotein I antibody on factor va degradation by activated‐protein C and its cofactor protein S
Authors: Matsuda Juzo , Gohchi Kengo , Kawasugi Kazuo , Gotoh Moritaka , Saitoh Noriko , Tsukamoto Miyo
Published: February 2007

We investigated the influence of anti‐β2‐glycoprotein I (aGPI), which recently has come to be regarded as anti‐cardiolipin antibody (aCL) itself, on factor Va (FVa) degradation by activated protein C/protein S system. We found that aGPI had an inhibitory effect on FVa degradation with β2‐glycoprotein I‐dependency, thus suggesting aGPI/aCL is a highly possible factor as the pathogenesis of thrombosis observed in aGPI/aCL‐positive patients. © 1995 Wiley‐Liss, Inc.
Treatment of aggressive Non‐Hodgkin's lymphoma in the elderly
Authors: Novitzky Nicolas , King Helen S. , Johnson Carol , Jacobs Peter
Published: February 2007

A nonanthracycline‐containing chemotherapeutic combination for the treatment of intermediate and high‐grade non‐Hodgkin's lymphoma was evaluated. Thirty‐four consecutive and previously untreated patients, with a median age of 75 (range 54‐86) years, with aggressive lymphoma, received daily etoposide (60 mg/m2 intravenous infusion [IVI]), cytosine arabinoside (50 mg/m2 subcutaneously), and methylprednisolone (60 mg/m2 IVI) on each of 5 consecutive days. Individuals with limited disease (stages I and II) (n = 9) received six, 3‐day cycles of the same therapy and involved field radiation (36 Gy in 20 fractions) between the third and fourth courses. Patients with disseminated lymphoma (n = 25) received 10 cycles over 8 months of the same combination, with the addition of methotrexate (200 mg/m2 on days 8 and 15), followed by leucovorin rescue (10 mg/m2 orally every 6 hr for 8 doses).

Of the 34 patients, 44% entered complete remission (CR), and 7 died before completing the first cycle of chemotherapy. Fifty‐six percent of the patients with limited disease and 40% with disseminated lymphoma (P > 0.05) achieved CR. For all patients, median survival was 14 months (range 3 days‐>54 months), this being 12 and 15 months, respectively. For the entire population of responding patients, median survival has not been reached at a median follow‐up of 39 months, while the median CR duration is 21 months. Ten of the 15 responders are alive in unmaintained CR at a median of 41 (range 30‐54) months. Myelotoxicity was the major side effect, leading to adjustments in dose and schedule in two‐thirds of the patients, although treatment changes did not affect outcome. Of the 15 deaths that occurred in this trial, in 53.3% it was unrelated to lymphoma or its therapy. Four patients that had achieved CR died of cardiovascular events (n = 2) or of progressive second malignancies (n = 2).

It is concluded that cytosine arabinoside in combination regimens is effective in selected patients; this is particularly relevant in the elderly. © 1995 Wiley‐Liss, Inc.
Large molecule fraction of plasma separated with polyethylene glycol in treatment of chronic relapsing thrombotic thrombocytopenic purpura
Authors: Fujita Masahiro , Ito Kazuhiko , Koyama Tetsuji , Shino Kazuko , Norioka Mihoko , Kashii Saburo , Kawamoto Hiroshi , Monden Sumie , Kakishita Eizo , Okuma Minoru
Published: February 2007

Plasma exchange and plasma infusion are effective in the treatment of patients with thrombotic thrombocytopenic purpura (TTP). It has been proposed that some component in normal plasma may be deficient in TTP patients. In this experiment normal plasma was fractionated and an effective fraction for the treatment of TTP was sought. Plasma was fractionated with 5% polyethylene glycol and a large molecule fraction was obtained which was composed mainly of proteins and lipoproteins with molecules larger than that of IgG. The fraction was dissolved in physiological saline and infused in two patients with chronic relapsing TTP who had been successfully treated periodically with plasma infusion. Peripheral platelet counts and serum LDH levels were measured, and the efficacy of the treatment was assessed. Infusion of the large molecule fraction elevated platelet counts and lowered the LDH level. However, the efficacy of the large molecule fraction was 25 to 50% that of plasma. Components in the fraction may have been inactivated partially during preparation. We propose that the large molecule fraction contains factors which are effective in some patients with TTP. © 1995 Wiley‐Liss, inc.
Familial myelodysplastic syndrome with onset late in life
Authors: Marsden Katherine , Challis David , Kimber Roger
Published: February 2007

A family is described in which three, and possibly four members, namely, the propositus, two paternal uncles, and possibly his paternal grandfather, developed a myelodysplastic syndrome (MDS) after the age of 60 years. This late onset resembles sporadic cases which are commoner in older age, rather than the previously reported familial cases most of whom have been children or young adults. The three affected members had megaloblastoid bone marrows with an increased proportion of bone marrow blasts and developed progressive bone marrow failure without leukemic transformation. The propositus showed a dramatic but temporary response to GM‐CSF therapy but eventually became unresponsive with a marked increase in bone marrow reticulin and reduction in hemopoietic elements. Affected members had no recognisable bone marrow cytogenetic abnormality but the pattern of inheritance and similarity in clinical features suggest an inherited genetic defect which predisposes to the development of MDS. © 1995 Wiley‐Liss, Inc.