bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunoblastic Lymphadenopathy-Like T Cell Lymphoma Evolving into a Massive Plasma Cell Proliferation with Biclonal Paraproteinemia
Authors: Higuchi Takakazu , Tada Jun-ichi , Mori Hiraku , Niikura Haruo , Omine Mitsuhiro , Kishimoto Koji , Tate Genshu , Mitsuya Toshiyuki
Published: April 2003

We present a case of immunoblastic lymphadenopathy-like T cell lymphoma (IBL-T) who subsequently developed a massive proliferation of plasma cells. At diagnosis of IBL-T, the patient had polyclonal hypergammaglobulinemia and subsequently, while on chemotherapy, developed paraproteinemia with biclonal peaks and the IBL-T lesion was replaced with a massive proliferation of CD38-positive plasma cells. The evolution was not likely to be attributed to a new neoplastic proliferation of B cells. It appeared that two B cell clones possibly had a growth advantage among the polyclonal B cells due to a depletion of suppressor T cells or to a disturbance in the immune system.
Storage of Iron in Bone Marrow Plasma Cells
Authors: Wulfhekel U. , Düllmann J.
Published: April 2003

The physiological site of iron storage in the human bone marrow is the macrophage (orthotopic iron store). Iron-storing plasma cells, as bone marrow indicators of iron overload, and/or chronic alcoholism represent a pathological (heterotopic) iron store. They were demonstrated by light and electron microscopy in 23 iron-overloaded patients: transfusional siderosis (n = 8), genetic haemochromatosis (GH; n = 11), iron-loading anaemias (n = 4) and in patients with bone marow impairment due to chronic alcoholism (n = 6). The pattern of iron storage in bone marrow plasma cells was monitored during iron loading in patients receiving continuous transfusional therapy (n = 7) and also upon reversal of iron overload by repeated phlebotomies in GH (n = 9) and in iron-loading anaemias (n = 4). The first ultrastructural evidence of iron storage in plasma cells was the appearance of free ferritin molecules in the cytosol, thus indicating endogenous ferritin synthesis. Accumulation of iron proceeded with the additional formation of ferritin- and haemosiderin-containing lysosomes (siderosomes) in these cells. Lysosomal ferritin partially showed a paracrystalline arrray. The siderosomes originated from autophagocytosis of cytoplasmic areas containing free ferritin molecules. In addition, the formation of ferritin-containing vesicles in the proximity of the Golgi apparatus was observed. The heterotopic iron store of bone marrow plasma cells was less readily mobilizable by blood-letting than the orthotopic store of macrophages.
Hypercoagulability in a Patient with Hypodysfibrinogenemia:Implic ations for Clinical Management
Authors: Wulf G.G. , Unterhalt M. , Buchwald A. , Zenker D. , Kreuzer H. , Hiddemann W.
Published: April 2003

Dysfibrinogenemia accounts for approximately 0.7% of thrombophilia in patients with venous thromboembolic disease. In 20% of these patients, plasma thrombophilic dysfibrinogen is below 1.0 mg/ml, defining hypodysfibrinogenemia. We describe a young female patient, in whom hypodysfibrinogenemia was the cause of several severe thromboembolic events which occurred even under oral anticoagulation monitored by a standard prothrombin time (PT) test. In this patient, the standard PT test according to Quick underestimated the plasma coagulability in vivo, presumably due to the low levels of dysfunctional fibrinogen as the substrate of the thromboplastin reagent. A PT test supplemented with bovine plasma fibrinogen (Thrombotest) revealed lower fibrinogen-independent international normalized ratio (INR) values in the proposita on oral anticoagulation compared to a control group with eufibrinogenemia. Monitoring therapy with the fibrinogen-independent Thrombotest secured safe anticoagulation in this patient. We suggest to consider PT tests with exogenous fibrinogen (e.g. Thrombotest) to monitor oral anticoagulation in the rare thrombophilic patients with hypodysfibrinogenemia.
A Case of ALK-Positive Large T-Cell Lymphoma Expressing Epithelial Membrane Antigen with Favorable Prognosis
Authors: Sawatsubashi Motohiro , Fukushima Noriyasu , Satoh Toshimi , Tsuda Kuniyoshi , Shin Takemoto , Tokunaga Osamu
Published: April 2003

We describe the case of a 59-year-old woman with Ki-1-negative, T cell-type, anaplastic lymphoma kinase (ALK)-positive large cell lymphoma that was positive for epithelial membrane antigen. She was histopathologically diagnosed as having a metastatic undifferentiated carcinoma from a cervical lymph node biopsy. Clinical and radiographic studies revealed no other primary tumor. The patient underwent a left radical neck dissection. Surgically resected lymph nodes revealed an ALK1-positive large cell lymphoma. Thereafter the patient has had an unusually favorable prognosis.
Flow-Cytometric Analysis of Leukocyte Alkaline Phosphatase in Myelodysplastic Syndromes
Authors: Okamoto Takahiro , Okada Masaya , Yamada Shu , Fujimori Yoshihiro , Takemoto Yoshinobu , Masuhara Kensaku , Kakishita Eizo
Published: April 2003

The expression of leukocyte alkaline phosphatase (LAP) in neutrophils is reduced in some patients with myelodysplastic syndrome (MDS). We quantitatively assayed for LAP in MDS leukocytes by a flow cytometry based method using a monoclonal antibody raised against human bone alkaline phosphatase. The LAP expression was assayed in blood samples from a group of 46 MDS patients, consisting of 39 patients with refractory anemia (RA), 3 with RA with excess blasts (RAEB), and 4 patients with RAEB in transformation. The percentage of LAP-positive cells was significantly higher in the MDS patients than in the normal subjects and also higher in RA than in RAEB and RAEB in transformation. To investigate the cause of the elevated LAP expression, we measured the serum concentrations of several cytokines. The granulocyte colony-stimulating factor (G-CSF) level was significantly elevated in MDS patients, and the serum G-CSF concentration clearly correlated with the percentage of LAP-positive cells. Thus, the LAP activity in RA is higher than in normal subjects, and G-CSF is thought to be one of the causes stimulating LAP expression in MDS neutrophils.
Rituximab (Anti-CD20 Monoclonal Antibody) Administration in a Young Patient with Resistant B-Prolymphocytic Leukemia
Authors: Vartholomatos G. , Tsiara St. , Christou L. , Panteli A. , Kaiafas P. , Bourantas K.L.
Published: April 2003

Following the administration of the human anti-CD20 monoclonal antibody IDEC-C2B8 (rituximab), a 31-year-old woman with B-prolymphocytic leukemia, who had been resistant to CHOP, fludarabine, pentostatin and 2-CdA, achieved complete remission. Rituximab was administered intravenously once a week for 4 weeks. The patient only had mild but tolerable side effects during the first cycle of therapy. She remains in complete remission 8 months following the discontinuation of treatment.
Apoptosis, bcl-2 Expression and p53 Accumulation in Myelodysplastic Syndrome, Myelodysplastic-Syndrome-Derived Acute Myelogenous Leukemia and de novo Acute Myelogenous Leukemia
Authors: Kurotaki Hidekachi , Tsushima Yaeko , Nagai Kazunori , Yagihashi Soroku
Published: April 2003

Apoptosis and its dysregulation have been implicated in dysplastic and ineffective hematopoiesis and the neoplastic transformation of bone marrow in myelodysplastic syndrome (MDS). To explore the role of apoptosis in hematological disorders, we examined the frequency of apoptotic cells by the in situ end labeling method in bone marrow specimens from 37 patients with MDS [refractory anemia (RA) 10 cases, RA with excess of blasts (RAEB) 27 cases including 12 cases with leukemic transformation], 12 patients with MDS-derived acute myelogenous leukemia (AML) and 13 patients with de novo AML. In addition, we investigated the relationship of apoptosis to the immunohistochemical expression of bcl-2 and p53 in these cases, and the association of apoptosis, bcl-2, and p53 with the leukemic evolution of MDS by examining sequential bone marrow samples of the same patient from the time of initial diagnosis to the time of overt leukemia. The percentage frequency of apoptotic cells was significantly greater in MDS (RA: 9.46 ± 2.99%, m ± SD; RAEB: 5.60 ± 3.09) as compared with those in MDS-derived AML (0.62 ± 0.37), de novo AML (0.28 ± 0.11) and controls (1.00 ± 0.59). On the other hand, the cases of RAEB with leukemic transformation exhibited a lower frequency of apoptotic cells and a higher frequency of bcl-2- and p53-positive cells than those without transformation. When the RAEB cases transformed to AML, the frequency of apoptotic cells was significantly reduced (2.96 ± 1.54 → 0.62 ± 0.37), while the frequencies of bcl-2-positive cells and p53-positive cells were greater (10.88 ± 3.66 → 30.54 ± 7.14, and 20.21 ± 6.21 → 32.34 ± 14.71, respectively). In contrast to MDS-derived AML, over a half of de novo AML cases showed few p53-positive cells. These findings corroborate the earlier notion that apoptosis may play a substantial role in dysplastic and ineffective hematopoiesis in MDS. It is also suggested that the suppression of apoptosis associated with enhanced bcl-2 expression and p53 accumulation increases the probability of developing leukemia in MDS, and that oncogenetic development might be different between MDS-derived AML and de novo AML.
GM-CSF in Sickle Cell Anemia Patients with Elevated Hb F
Authors: Haider M.Z. , Raghupathy R. , Azizieh F. , Abdelsalam R. , D’Souza T.M. , Adekile A.D.
Published: April 2003

We estimated plasma GM-CSF levels in a group of 28 steady-state sickle cell anemia (SS) patients in Kuwait, using an ELISA technique. There were 24 age-matched Hb AA controls, 14 of whom were healthy while 10 were acutely ill at the time of the study. Five SS patients were also studied during 6 episodes of painful crisis. Among the SS patients, 82.1% were homozygous for the Saudi Arabia/India (SAI) haplotype with Hb F ranging from 15 to 35% and total Hb from 8.5 to 11 g/dl. Three patients (siblings) were SAI/Benin compound heterozygotes with Hb F of 9–23% and total Hb >10 g/dl. One patient each was homozygous for the Benin or the Bantu haplotype; they had Hb F <2% and total Hb of 6.6 and 7.2 g/dl, respectively. Four (14.3%) steady-state SS patients had detectable plasma GM-CSF ranging from 75 to 1,817.6 pg/ml. These included the 2 patients with Hb F <2.0% and 2 with the SAI/Benin compound heterozygotes with Hb F of 11 and 9%, respectively. Four (66.7%) SS patients in crisis, 6 (42.9%) healthy controls and 6 (60%) acutely ill controls had detectable plasma GM-CSF. A clearcut association of GM-CSF with Hb F level or degree of anemia in steady-state SS patients could not be established. The appearance of GM-CSF in the plasma of patients in crisis and also among control subjects raises the possibility that other factors are involved in the production of this cytokine in the subjects studied.
Efficacy of Further Attempts to Mobilize CD34+ Peripheral Stem Cells with Alternative Procedures after Primary Failure
Authors: Kröger N. , Rauhöft C. , Zeller W. , Renges H. , Hassan H.T. , Krüger W. , Schuch G. , Wacker-Backhaus G. , Colberg H. , Kuse R. , Gutensohn K. , Löliger C. , Zander A.R.
Published: April 2003

19 patients who failed the target collection of at least 2.5 × 106 CD34+ cells/kg underwent further mobilization procedures either with granulocyte-colony-stimulating factor (G-CSF) alone after failure to chemotherapy plus G-CSF (group 1), or with chemotherapy plus G-CSF (group 2), or with high-dose G-CSF (24 μg/kg) alone (group 3) after failure to respond to standard dose of G-CSF (10 μg/kg) alone. In all groups, an increase in median CD34+ cell yield could be observed following alternative procedures (1.1- to 1.9 × 106 kg; p = 0.02). The highest increase in CD34+ cell harvest was achieved in group 1 (0.85 to 2.2 × 106 kg), followed by group 2 (1.2 to 1.7) and group 3 (1.0 to 1.4), but without statistically significant difference between the mobilization technologies. All patients with more than 1.0 × 106 CD34+ cells/kg in the first apheresis procedure reached the overall target of 2.5 × 106 CD34+ cells/kg after a second or subsequent mobilization procedure. In contrast, only 3 of 8 patients (37%) with less than 1.0 × 106 CD34+ cells in the first harvest could reach the target of 2.5 × 106 CD34+ cells after further mobilization attempts.
Are Haemochromatosis Mutations Related to the Severity of Liver Disease in Hepatitis C Virus Infection?
Authors: Martinelli Ana L.C. , Franco Rendrik F. , Villanova Marcia G. , Figueiredo José F.C. , Secaf Marie , Tavella Marli H. , Ramalho Leandra N.Z. , Zucoloto Sérgio , Zago Marco A.
Published: April 2003

It has been proposed that iron overload may adversely affect liver disease outcome. The recent identification of 2 mutations in the HFE gene related to hereditary haemochromatosis (Cys282Tyr and His63Asp) provided an opportunity to test whether they are associated with hepatic iron accumulation and the activity and severity of liver disease in hepatitis C virus (HCV) infection. We investigated the prevalence of HFE mutations in 135 male patients with chronic HCV hepatitis, and correlated genotype distribution with different parameters of iron status and the activity and severity of liver disease. Of these 135 patients, 6 (4.4%) carried Cys282Tyr and 32 (23.7%) carried His63Asp, frequencies which were similar to those observed in healthy controls. Serum iron levels and transferrin saturation (but not ferritin levels or liver iron content) were significantly higher in carriers than in non-carriers of HFE mutations. No difference was observed in serum ALT, AST and GGT levels between carriers and non-carriers. Finally, scores for necroinflammatory activity and fibrosis in the liver were significantly higher in HFE carriers than in non-carriers. Patients with chronic HCV infection carrying HFE mutations tend to present more evident body iron accumulation and a higher degree of necroinflammatory activity and fibrosis in the liver. HFE gene mutations might be an additional factor to be considered among those implicated in the determination of a worse prognosis of the liver disease in chronic HCV infection.
Cure from Severe Aplastic Anemia in vivo and Late Effects
Authors: Socié Gérard , Gluckman Eliane
Published: April 2003

Recent progress in the treatment of aplastic anemia has dramatically changed the previously grim prognosis for these patients. Improvements in bone marrow transplantation and immunosuppression have increased the number of long-term survivors so that immediate survival is no longer the sole concern. Here, were review the major clinical studies and summarize recent analyses of late malignant and nonmalignant complications following treatment of aplastic anemia.
Effect of Training on the Phagocytic Capacity of Peritoneal Macrophages from Rats Exposed to Swim Stress
Authors: Salman Hertzel , Bergman Michael , Bessler Hanna , Weiss Jonathan , Punsky Igor , Djaldetti Meir
Published: April 2003

Since strenuous effort may affect the immune system, a study was designed to examine the impact of the progressive training of rats exposed to swim stress. Rats (trained swimmers) were forced to swim daily in a water bath for progressively longer periods. At the end of the study, which continued for a total of 6 weeks, the superoxide anion generation and phagocytic capacity of peritoneal macrophages, the mitogen response of splenic cells (splenocytes) and the serum corticosterone level were examined. The results, compared to those of animals taken in and out of their cages (nonswimmers), showed an increase in superoxide anion generation, as well as a decrease in both the percentage of phagocytosing cells and the number of particles internalized by each individual cell. In trained swimmers, the mitogen response to phytohemagglutinin and concanavalin A (Con A), as well as the corticosterone level, did not change significantly from those of nonswimmers. A third group of animals were forced to swim once only for 30 min, until the appearance of signs of marked fatigue (acute swimmers). Their peritoneal macrophages showed an increased superoxide anion generation and a significantly decreased response to Con A compared to those of the nonswimmers. The serum corticosterone level in acute swimmers was found to be increased compared to that of an additional group of animals kept at complete rest. The findings indicate that the progressive training of rats exposed to swim stress does not prevent alterations in certain immune responses, a fact that should be considered by intensive exercisers.
Basic Fibroblast Growth Factor Modulates the Surface Expression of Effector Cell Molecules and Primes Respiratory Burst Activity in Human Neutrophils
Authors: Takagi Satoshi , Takahashi Kimiko , Katsura Yoshiya , Matsuoka Takeshi , Ohsaka Akimichi
Published: April 2003

Basic fibroblast growth factor (b-FGF) mediates a variety of biological responses such as angiogenesis and hematopoiesis. We examined the effect of b-FGF on human neutrophil functions in vitro. The surface expression of effector cell molecules on neutrophils was determined by flow cytometry and monoclonal antibodies. b-FGF increased the expression of CD11b leukocyte integrin and complement receptor type 1 on neutrophils and decreased the expression of L-selectin on neutrophils in a dose- and time-dependent manner. We also examined the effect of b-FGF on the respiratory burst activity in neutrophils. Although b-FGF alone did not induce intracellular oxidative product formation by neutrophils, it enhanced H2O2 production in neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine or phorbol myristate acetate. These findings suggest that b-FGF may participate in the inflammatory process via modulating the surface expression of effector cell molecules and enhancing respiratory burst activity in neutrophils.
Diagnosis of Granulocytic Sarcoma by Fine-Needle Aspiration Cytology
Authors: Bangerter Markus , Hildebrand Annette , Waidmann Oliver , Griesshammer Martin
Published: April 2003

Granulocytic sarcoma (GS) occurs in patients with chronic myeloproliferative disorders as well as in patients with acute myeloid leukemia (AML). These tumorous masses can occur anywhere in the body and have to be differentiated from lymphoma, carcinoma or infectious processes. We report the results of fine-needle aspiration cytology (FNAC) in 26 patients with GS. Seventeen patients suffered from AML and 9 from chronic myeloid leukemia (CML) blast crisis. In 5 patients with AML, GS was the initial presentation of hematological malignancy, in the remaining 21 patients, FNAC confirmed relapse of AML or extramedullary blast crisis of CML. In 8 patients, GS was located in the skin, in 17 in the lymph node and in another patient in the spinal canal. This study demonstrates the clinical utility and diagnostic accuracy of FNAC in the evaluation of GS from multiple sites.
Mycoplasma-pneumoniae-Induced Thrombotic Thrombocytopenic Purpura
Authors: Bar Meir E. , Amital H. , Levy Y. , Kneller A. , Bar-Dayan Y. , Shoenfeld Y.
Published: April 2003

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease characterized by widespread platelet aggregation, hemolytic anemia and fever with renal and neurological involvement. Different factors have been associated with the development of TTP, e.g. infections, pregnancy, chemotherapy, drug therapy and bone marrow transplantation. Recent data imply that all these different causes may induce the disease by decreasing the activity of the plasma von Willebrand factor-cleaving protease resulting in unusually large von Willbrand factor multimers that later on initiate the cascade of TTP. In this communication, we present a unique association between infection with Mycoplasma pneumoniae and TTP. We believe that the emergence of antibodies that cross-react with Mycoplasma and the protease might elucidate in this case the pathogenesis of TTP.
Secondary Cutaneous Infiltration in B Cell Chronic Lymphocytic Leukemia
Authors: Várkonyi Judit , Zalatnai Attila , Timár József , Matolcsi András , Falus András , Bencsáth Márta , László Valéria , Pócsik Éva , Kotlán Beáta , Császár Albert
Published: April 2003

We describe a patient presenting with B cell chronic lymphocytic leukemia (B-CLL) who subsequently developed cutaneous infiltrates. Specimens of the blood, bone marrow and cutaneous infiltrations all showed the same heavy-chain gene rearrangement. Following failure of conventional chemotherapy, and in view of the similarity of the disease to cutaneous T cell lymphoma, interferon-α therapy was employed with satisfactory results. Introduction of this cytokine to the therapeutic modalities for secondary cutaneous B-CLL would hopefully change the poor outcome of this entity, or at least could produce a better quality of life. Loss of histidine decarboxylase activity in the infiltrating cells – in contrast to circulating lymphocytes – may be associated with the transformation of B-CLL to a more aggressive infiltrative form, offering a possible explanation for tissue invasiveness. The changing character of the disease raises the possibility of a second mutational event in the course of B-CLL.
p53 Pathway in Apoptosis Induced by All-Trans-Retinoic Acid in Acute Myeloblastic Leukaemia Cells
Authors: Zheng A. , Mäntymaa P. , Säily M. , Savolainen E.-R. , Vähäkangas K. , Koistinen P.
Published: April 2003

The role of the p53 pathway in apoptosis induced by all-trans-retinoic acid (ATRA) was studied in 5 human acute myeloid leukaemia (AML) cell lines, OU-AML-3, -4, -5, -7 and -8, previously established and characterized by the authors. Although all the cell lines have a wild-type (wt) p53 gene, the protein is in a mutant conformation detectable by the anti-p53 antibody PAb 240. Exposure of the cell lines to 1.0 μM ATRA for 72 h caused induction of apoptosis detectable by morphology and the annexin V assay. The number of apoptotic cells according to the annexin V assay varied from 16 ± 8% (OU-AML-7) to 61 ± 4% (OU-AML-3) in ATRA-treated cells, while it was 7 ± 6% in control cells. Western blotting and flow cytometry showed down-regulation of the p53 protein by ATRA. The conformation of p53 remained unchanged, being detectable in flow cytometry by PAb 240, but not by PAb 1620 (an antibody which only detects p53 in wt conformation). At the same time bcl-2 was down-regulated as shown by Western blotting and flow cytometry, while no induction of bax was observed by ATRA. On the basis of these results, ATRA-induced apoptosis in these AML cell lines is independent of the p53 pathway, although it is associated with the down-regulation of bcl-2.
Th1 and Th2 Cytokine Profiles in Sickle Cell Disease
Authors: Raghupathy R. , Haider M.Z. , Azizieh F. , Abdelsalam R. , D’Souza T.M. , Adekile A.D.
Published: April 2003

We have investigated the levels of Th1 (IL-2 and IFN-γ) and Th2 (IL-4) cytokines in the plasma and supernatants following peripheral blood mononuclear cell culture and mitogen stimulation in a group of 39 patients with sickle cell disease (SCD) made up of 29 SS, 8 Sβ-thal and 2 Hb SD in steady state. Five SS patients were studied during 7 episodes of vaso-occlusive crisis. Twenty-four control (3 Hb AS and 21 Hb AA) were also studied; 10 were acutely ill while 14 were healthy at the time of the study. The plasma levels of IL-2 and IFN-γ were similar in the patients and the controls. However, plasma IL-4 was significantly higher among the steady-state SS patients than in the controls. While there was no significant difference in cytokine levels following mitogen stimulation in the different groups, plasma IL-2 to IL-4 and IFN-γ to IL-4 ratios were significantly lower among the steady-state SS patients, indicating a possible Th2 bias in our sickle cell patients and suggesting a possible mechanism to explain the predisposition of SCD patients to bacterial infections. However, SS patients with good splenic function showed a relative Th1 bias, which may be an additional explanation for the protection against bacterial infections in such patients.
Granulocytic Sarcoma with Breast and Skin Presentation: A Report of a Case Successfully Treated by Local Radiation and Systemic Chemotherapy
Authors: Breccia Massimo , Petti Maria Concetta , Fraternali-Orcioni Giulio , Monarca Bruno , Latagliata Roberto , D’Elia Gianna Maria , Mandelli Franco , Pileri Stefano Aldo
Published: April 2003

Granulocytic sarcoma (GS) is a rare extramedullary tumor composed of immature myeloid cells. It is usually associated with leukemia or other myeloproliferative disorders, but can also occur without overt hematologic disease, i.e. in patients with a normal bone marrow and no history of acute myelogenous leukemia. This primary extramedullary lesion may indeed represent a diagnostic and therapeutic dilemma for both the hematopathologist and oncologist. We describe a case of GS diagnosed in a nonleukemic patient and review the literature regarding the pathologic features and treatment of this condition.
IgD Multiple Myeloma Preceding the Development of Extensive Extramedullary Disease without Medullary Involvement
Authors: Iwasaki Tsuyoshi , Hamano Teruaki , Ogata Atsushi , Hashimoto Naoaki , Kakishita Eizo
Published: April 2003

We present a unique case of IgD multiple myeloma (MM) preceding the development of extensive extramedullary disease without medullary involvement. A 63-year-old man was diagnosed with IgD-λ MM when he developed anemia. After 3 months of chemotherapy, he was in complete remission as evidenced by the disappearence of bone marrow (BM) plasmacytosis, monoclonal IgD protein in his serum, and Bence Jones proteinuria. Six months after diagnosis, his disease took an unusual course with the development of plasmacytomas in the skin, without medullary involvement. He then received chemotherapy, resulting in the complete disappearance of the subcutaneous plasmacytomas. Two years after the initial diagnosis, his disease took an aggressive clinical course with retroperitoneal relapse, leading to the patient’s death within 1 month. The two separate episodes of extramedullary disease were associated with elevated serum lactic dehydrogenase levels and the absence of plasma cells in the BM. This case provides evidence of two separate transformations of the original malignant MM clone.
Sudden Bilateral Deafness from Hyperleukocytosis in Chronic Myeloid Leukemia
Authors: Resende L.S.R. , Coradazzi A.L. , Rocha-Júnior C. , Zanini J.M. , Niéro-Melo L.
Published: April 2003

Sudden-onset bilateral deafness as a clinical manifestation of hyperleukocytosis in chronic myeloid leukemia (CML) is a rare occurrence. We found only 27 clinical descriptions in 16 published papers. In this work, the authors present a review on deafness in CML and describe a new case with prominent hyperleukocytosis, where the neurological findings suggest slowing of the circulation through small blood vessels in the brainstem as the cause of deafness. The evolution was good after treatment. To our knowledge, this is the second case documented with electrical auditory brainstem-evoked potentials and the first with magnetic resonance imaging.
Renal Trauma and the Risk of Long-Term Complications in Shock Wave Lithotripsy
Authors: Evan Andrew P. , Willis Lynn R. , Lingeman James E. , McAteer James A.
Published: April 2003

Open surgery for removal of upper urinary tract stones has long been associated with a high morbidity and mortality. So when shock wave (SW) lithotripsy (SWL) was introduced in the early 1980s, the climate was right for acceptance of a noninvasive method for stone comminution. The growth in popularity of SWL was extremely rapid, based in part on the perception that it was entirely safe [1]. Now, after a decade of clinical SWL, experience tells us differently. SWL may be very effective at breaking kidney stones, but it can also cause severe renal trauma that can lead to irreversible long-term complications [2, 3].
More on Heparin-Associated Thrombocytopenia
Authors: Berlot Giorgio , Lucchese Francesca
Published: April 2003

Even if we appreciate Dr. Fisher’s remarks, we still do not feel that our approach has been inadequate. Our opinion is based on some evidence, although we could not perform any laboratory investigation to better define the type of heparin-associated thrombocytopenia (HAT) [1]. First, as is clearly demonstrated in figure 1 of our paper, the platelet count started to decrease on the day following the administration of heparin [2]. In our patient, we could exclude any previous exposure to heparin, which, according to the current literature, represents a prerequisite for the occurrence of HAT II immediately following the initiation of heparin therapy. In the absence of such an exposure, HAT II is reported to occur after some days of heparin treatment [3].
Correlation of Serum Magnesium and Serum Lipid Levels in Hemodialysis Patients
Authors: Robles N.R. , Escola J.M. , Albarran L. , Espada R.
Published: April 2003

Abnormalities in lipid and/or protein content of lipoprotein have been described in patients with chronic renal failure [1, 2]. Hypertriglyceridemia occurs in 50–75% of patients with chronic renal insufficiency. Although hypercholesterolemia is rare in uremic and dialyzed patients, decreased high-density-lipoprotein (HDL) cholesterol (HDL-C) concentration has been documented [3]. Magnesium retention is also a problem in patients on maintenance hemodialysis: the majority of dialysis patients present with hypermagnesemia [4]. Magnesium deficiency has a possible role in the perturbation of lipid metabolism in the non uremic population [5, 6]. Furthermore, it has been shown that in uremic rats magnesium deficiency worsens several serum lipid parameters [7]. We have studied the relation of serum magnesium and plasma lipid levels in uremic hemodialysis patients.
Peritonitis per Patient and Year: A Basic Index
Authors: Morey A. , Lima C. , Rapado C. , Losada G.P. , Marco J.E.
Published: April 2003

For the past 15 years, the appropriate treatment of end stage renal failure has included both continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis. In some circumstances CAPD has been indicated as a more adequate option. However, the main handicap for CAPD patients is peritoneal infection [1], ranking as the main cause of hospital admission and transfer to haemodialysis [2]. Peritonitis represents the third highest cause of death in CAPD patients [3]. It also produces a 15–19% deterioration of peritoneal membrane function.
Lipid Composition of Platelets in Patients with Uremia
Authors: Vecino A. , Navarro-Antolín J. , Teruel J. , Navarro J. , Cesar J.
Published: April 2003

Aims: The lipid composition of platelets and the function of these cells in patients with uremia were studied. Methods: Fourteen patients and 14 normal volunteers were studied. Platelet lipids including phospholipids and cholesterol, as well as the platelet aggregation response to agonists, were studied. Results: The amount of platelet phospholipids was decreased in patients compared to controls (338.0 ± 79 vs. 511.6 ± 125 nmol/109 cells; p < 0.001), while the percentage of the five main specimens of these compounds was normal. The content of platelet cholesterol in patients (97.8 ± 17.0 µg/109 cells) was similar to that in controls (91.7 ± 26.0 µg/109 cells). Consequently, the cholesterol:phospholipid ratio in uremic platelets was increased (0.75 ± 0.1 vs. 0.46 ± 0.1; p < 0.01). Although this feature is associated with hyperreactive platelets, the aggregation tests were defective for adenosin diphosphate (p < 0.01), arachidonic acid (p < 0.01), epinephrine (p < 0.01) and collagen (p < 0.001). This behavior is probably due to the multifactorial platelet defect described in uremia.
Sera of IgA Nephropathy Patients Contain a Heterogeneous Population of Relatively Cationic Alpha-Heavy Chains
Authors: Shuib A.S. , Chua C.T. , Hashim O.H.
Published: April 2003

Sera of IgA nephropathy (IgAN) patients and normal subjects were analysed by two-dimensional (2-D) gel electrophoresis. Densitometric analysis of the 2-D gels of IgAN patients and normal subjects revealed that their protein maps were comparable. There was no shift of pI values in the major α-heavy chain spots. However, the volume of the α-heavy chain bands were differently distributed. Distribution was significantly lower at the anionic region in IgAN patients (mean anionic:cationic ratio of 1.184 ± 0.311) as compared to normal healthy controls (mean anionic:cationic ratio of 2.139 ± 0.538). Our data are in support of the previously reported findings that IgA1 of IgAN patients were lacking in sialic acid residues.
Urinary Transforming Growth Factor-β (TGF-β) Excretion and Renal Production of TGF-β in Rats with Subtotal Renal Ablation: Effect of Enalapril and Nifedipine
Authors: Monteiro de Freitas Alexandre S. , Coimbra Terezila M. , Costa Roberto S. , Baroni Edmara A.
Published: April 2003

The aim of the present study was to investigate the effect of enalapril and nifedipine on renal transforming growth factor-β (TGF-β) production and on the rate of urinary TGF-β excretion in rats with subtotal renal ablation. After subtotal nephrectomy some animals were treated with enalapril or nifedipine. Renal cortical TGF-β mRNA levels were 68% higher in untreated nephrectomized rats (p < 0.05) and 39% higher in rats treated with nifedipine (p < 0.05) compared with controls. There was no difference in renal cortical TGF-β mRNA content between the nephrectomized rats treated with enalapril and sham animals, showing that enalapril treatment prevented the increase of TGF-β mRNA in nephrectomized rats. The rate of urinary TGF-β excretion was 2.2 ± 0.8 pg/min in sham animals, 61.5 ± 40.1 pg/min in untreated nephrectomized rats, 9.6 ± 4.2 pg/min in nephrectomized rats treated with enalapril, and 55.2 ± 24.46 pg/min in rats treated with nifedipine. The immunohistochemical reaction for TGF-β in the renal cortex was less intense in the nephrectomized rats treated with enalapril than in the other groups of rats with subtotal renal ablation. These data show that enalapril induces a decrease in renal TGF-β production and in urinary TGF-β excretion in rats with subtotal renal ablation, an effect associated with the protective action of this treatment on renal structure and function and suggest that the determination of the rate of urinary TGF-β could be a useful procedure for the evaluation of disease progression and therapeutic efficacy in the remnant kidney model.
Anti-CD8 Monoclonal Antibody Protects against Spontaneous IgA Nephropathy in ddY Mice
Authors: Shimamine Ryosuke , Shibata Ryujiro , Ozono Yoshiyuki , Harada Takashi , Taguchi Takashi , Hara Kohei , Kono Shigeru
Published: April 2003

We investigated the effects of anti-CD4 monoclonal antibody (mAb) and/or anti-CD8 mAb in ddY mice, an animal model of spontaneous IgA nephropathy. Female ddY mice were treated with 18 intravenous injections of anti-CD4 and/or anti-CD8 mAb at 2-week intervals. This was based on our observation that a single injection of anti-CD4 mAb or anti-CD8 mAb caused a selective depletion in CD4+ T cells for 2 weeks and CD8+ T cells for 4 weeks, respectively. The level of proteinuria, serum IgA, and changes in the histopathological features of renal tissue samples were assessed in treated mice between the age of 4 and 40 weeks. The level of proteinuria increased with age, but there was not significant difference among the groups. No animal developed microhematuria throughout the study. Treatment with anti-CD4 mAb produced a mild to moderate level of mesangial hypertrophy at 20 and 40 weeks, similar to the results in untreated mice. The lowest degree of mesangial hypertrophy occurred in mice treated with anti-CD8 mAb up to the age of 40 weeks. Treatment with a combination of anti-CD4 and anti-CD8 mAbs produced effects that were similar to those observed on treatment with anti-CD8 mAb alone. Our results suggest that CD8+ T cells mediate mesangial proliferation and the progression of nephropathy in ddY mice.
Asymptomatic Childhood Hypertension
Authors: Scheinman Jon I. , Crevi Diana L. , Narla Lakshmana D. , Chan James C.M.
Published: April 2003

A patient with asymptomatic hypertension is presented in stages (small type) to an expert clinician who responds to the information, sharing his/her reasoning with the reader (regular type). The authors’ commentary follows.
Secondary Hyperparathyroidism in Severe Chronic Renal Failure Is Corrected by Very-Low Dietary Phosphate Intake and Calcium Carbonate Supplementation
Authors: Barsotti Giuliano , Cupisti Adamasco , Morelli Ester , Meola Mario , Cozza Vincenzo , Barsotti Massimiliano , Giovannetti Sergio
Published: April 2003

The main purpose of our study was to verify the effect of a very-low-protein, low-phosphorus diet, supplemented with essential amino acids and keto analogues and with calcium carbonate, on circulating levels of intact parathyroid hormone (i-PTH) in severe chronic renal failure patients with secondary hyperparathyroidism, not treated with any vitamin D preparation. To this aim, we shifted 21 chronic uremics (12 males, 9 females; age 56 ± 13 years) with serum creatinine >6.5 mg/dl and i-PTH >150 pg/ml, from a standard low-protein diet (0.6 g/kg/day approximately) to a very-low-protein (0.3 g/kg/day), very-low-phosphorus (5 mg/kg/day) diet supplemented with a mixture of essential amino acids and calcium keto analogues (Ketodiet), calcium carbonate (2–4 g/day), iron, and vitamin B12 preparations. The energy supply of both diets was 30–35 kcal/kg/day. Exclusion criteria were a poor compliance with dietary or supplement prescriptions or signs of autonomic hyperparathyroidism. After 4 ± 2 months of Ketodiet, the i-PTH serum levels decreased by 49% as a mean (from 441 ± 233 to 225 ± 161 pg/ml, p < 0.001); serum phosphorus and alkaline phosphatase decreased, whereas serum calcium increased. The great reduction of serum and urinary urea demonstrated a good compliance with Ketodiet, and no sign of protein malnutrition was observed. These findings confirm that even in severe chronic uremic patients dietary phosphorus restriction and calcium carbonate supplementation lower i-PTH serum levels. This is one of the goals of the dietary treatment that can be safely achieved, provided good compliance both with the dietary prescriptions and with adequate energy and supplement intakes.
Direct Method for the Measurement of Low-Density Lipoprotein Cholesterol Levels in Patients with Chronic Renal Disease: A Comparative Assessment
Authors: Akanji Abayomi O.
Published: April 2003

Background/Aim: This study was performed to comparatively evaluate the results obtained for low-density lipoprotein (LDL) cholesterol concentrations by either a newly described direct method or the Friedewald equation in subjects with and without chronic renal disease. Methods: Fasting plasma was obtained from a total of 169 subjects, 105 with normal renal function (including 53 hyperlipidaemic) and 64 with chronic renal disease (nephrotic syndrome and/or chronic renal failure; including 40 hyperlipidaemic patients), and analyzed for LDL cholesterol using the Friedewald equation and a direct LDL assay method. Results: The Friedewald equation and the direct LDL cholesterol assay correlated well with each other (r = 0.79–0.90 in all subjects with plasma triglyceride, TG, levels greater than or less than 4.0 mmol/l and with and without chronic renal disease and/or hyperlipidaemia, all p < 0.0001). The values for LDL cholesterol, however, tended to be higher with the direct measurement. This mean difference was trivial in hyperlipidaemic subjects with (8.5%) and without (7.1%) normal renal function (both p < 0.05), but could be clinically significant in those with TG >4.0 mmol/l (mean difference 18%, p < 0.001). Indeed, bias plots confirmed this observation of wider negative bias for Friedewald estimation in these moderately hypertriglyceridaemic subjects. Conclusion: For most routine laboratories the options immediately available for assessment of lipid levels are the Friedewald equation or the direct measurement. The Friedewald equation and the direct assay method for LDL cholesterol are about equally good for assessment of the LDL status in patients with chronic renal disease and plasma TG <4.0 mmol/l. Where there are restraints on laboratory budgets, it would appear appropriate that the more expensive direct assay method be restricted to cases in whom plasma TG >4.0 mmol/l or to patients who, for whatever reason, are unable to produce fasting samples.
Acute Volume Expansion and Salt-Loading Studies in Rats
Authors: Reddy S. , Salipan-Moore N. , Mildenberger S. , Willis N. , Györy Á.Z.
Published: April 2003

Differences have been postulated for the mechanism of natriuresis due to atrial natriuretic peptide (ANP), salt loading with high salt diet (HS) and acute volume expansion (AcVE), in particular between AcVE and ANP based on the observed synergism between the two. Therefore the effects of and the interaction between the three were investigated in rats. ANP and AcVE produced the same natriuresis in HS as in normal salt (NS) rats and, in both, the actions of ANP and AcVe were significantly additive showing similarity in mechanisms. Synergism [(AcVE + ANP) – AcVE] was, however, present only in the NS rats. Proximal tubular sodium transport was the same with AcVE and ANP+AcVE suggesting that synergism is a property of more distal nephron segments. In conscious HS rats, plasma ANP was significantly less but natriuresis was higher than in NS rats. ANP therefore probably has some causative role in the natriuresis of AcVE but none in that of HS loading. Urinary dopamine was significantly increased by HS and further increased by AcVE in both NS and HS rats, the relationship between dopamine and natriuresis being significantly positive (r2 = 0.328) reaching equivalent levels in both NS and HS rats. Systemic benserazide prevented the increase in urinary dopamine but only attenuated the natriuresis of AcVE. We conclude that HS does not potentiate the natriuresis of AcVE or ANP, synergism between AcVE and ANP is not a proximal tubule event and dopamine accounts for significant natriuresis of VE in addition to other natriuretic factors.
Study of Renal Metabolic Disturbances Related to Renal Lithiasis at School Age in Very-Low-Birth-Weight Children
Authors: Monge Margarita , García-Nieto Victor M. , Domenech Eduardo , Barac-Nieto Mario , Muros Mercedes , Pérez-González Ernesto
Published: April 2003

We studied 34 asymptomatic children who were born with a very-low-birth-weight (VLBW) and had no perinatal history of acute renal failure nor treatment with furosemide. The study was done at preschool or school age, looking for echographic changes and renal tubular disturbances which are known to predispose to renal lithiasis. The results were compared with those of a control group of 18 children who had been born at term with a body weight >2,500 g. One or more renal tubular disturbances were found in 64.70% of the VLBW children. Most frequently found were decreased ammonium excretion in response to furosemide (38.23%), enhanced N-acetylglucosaminidase excretion (35.29%), hypercalciuria (26.47%), and hypocitraturia (23.53%). Echography revealed renal cortical hyperechogenicity (17.65%) and renal lithiasis (8.82%) in some of the VLBW children. We found a significant positive correlation (r = 0.7) between the perinatal level of plasma phosphate and the total amount of H+ excreted in response to furosemide at preschool or school age. Because these renal tubular anomalies may be precursors of future lithiasis, and the renal function and echography tests are not invasive, we suggest that renal tubular function be measured and followed up in every VLBW child, particularly when perinatal hypophosphatemia has occurred.
Circulating Ionized and Total Magnesium in End-Stage Kidney Disease
Authors: Pedrozzi Nicola E. , Truttmann Anita C. , Faraone Rita , Descoeudres Claude E. , Wermuth Bendicht , Lüthy Christa M. , Nuoffer Jean-Marc , Frey Felix J. , Bianchetti Mario G.
Published: April 2003

Background: Circulating magnesium exists in the ionized state and in the undissociated form, either bound to albumin, or complexed to various anions. Until recently, only the measurement of total plasma magnesium has been possible. Now circulating ionized magnesium can be assessed as well. Methods: Total and ionized plasma magnesium were determined in 43 patients on maintenance hemodialysis (dialysate composition: calcium 1.75 mmol/l, magnesium 0.75 mmol/l) before a dialysis session and in a group of 23 healthy subjects. Results: The total (1.16 [1.03–1.31] versus 0.81 [0.78–0.89] mmol/l; median and interquartile range) and the ionized (0.71 [0.66–0.78] versus 0.54 [0.53–0.59] mmol/l) plasma magnesium levels were significantly higher (p < 0.01) and the ionized plasma magnesium fraction lower (0.61 [0.58–0.65] versus 0.67 [0.64–0.70]; p < 0.02) in patients than in controls. Conclusion: The determination of circulating ionized magnesium using selective electrodes is an attractive method to evaluate extracellular magnesium in kidney disease.
Glomerular Nonmuscle-Type Myosin Heavy-Chain Isoform Gene Expression in Glomerulosclerosis
Authors: Ebihara Isao , Kimura Kenjiro , Nakamura Tsukasa , Tomino Yasuhiko , Yazaki Yoshio , Nagai Ryozo , Koide Hikaru
Published: April 2003

This study was designed to assess how the glomerular expression of the nonmuscle-type myosin heavy-chain isoform, SMemb, is regulated in rats with focal glomerulosclerosis induced by puromycin aminonucleoside. SMemb was barely detectable in control glomeruli. On day 48 of focal glomerulosclerosis, SMemb was expressed in mesangial area and glomerular epithelial cells. When glomerulosclerosis became prominent on day 80, SMemb stained immunohistochemically in a focal segmental pattern in the sclerotic glomeruli. SMemb-expressing cells did not always express α-smooth muscle actin. In Northern blot analysis, SMemb mRNA was not detected in control glomeruli, whereas it was transiently upregulated in glomeruli on day 48 in rats with focal glomerulosclerosis. The mRNA levels of SMemb were thereafter gradually downregulated by day 80; however, they remained higher than those of control glomeruli. These data suggest that glomerular embryonic nonmuscle-type myosin heavy chain is abnormally regulated in glomerulosclerosis and that glomerulosclerosis may be associated with dedifferentiation of not only the mesangial cells, but also the other resident glomerular cells.
Biocompatibility of a Glucose-Free, Acidic Lactated Solution for Peritoneal Dialysis Evaluated by Population Analysis of Mesothelium
Authors: Wajsbrot Valeri , Shostak Avshalom , Gotloib Lazaro , Kushnier Raisa
Published: April 2003

Glucose-enriched, racemic lactate buffered solutions for peritoneal dialysis induce a significant reduction of cell viability as well as a hypertrophic, senescent phenotype of the exposed monolayer. The present study was designed to verify whether the aforementioned changes resulted form the buffer, from the osmotic agent, or from a combined effect of both. Mice were acutely (2 h) and long-term (15 and 30 days) exposed to daily intraperitoneal injections of a racemic lactate, heat-sterilized, low-pH (5.2), glucose-free solution. Imprints of the monolayer were taken at the end of each time interval. The glucose-free lactated buffer used in the present study did not induce significant changes in density distribution, mean cell size, mean cytoplasmic surface area, prevalence of large cells, multinucleation, proportion of observed cells in mitosis, and cell viability. So far, the previously mentioned hypertrophic phenotype appears to derive from substantial alterations in the cell cycle of mesothelium exposed to high concentrations of glucose and/or advanced glycosylation end products and unrelated to lactate.