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Background and Objectives: Homozygous beta-thalassemia patients may develop iron overload even if untransfused, due to inappropriately high intestinal iron absorption. Reduction of hepcidin synthesis has been reported both in patients and in animal models. We have measured liver hepcidin and other iron gene transcripts in two different mouse models of beta-thalassemia at different ages., Design and Methods: Mice Hbb(th/th), characterized by spontaneous homozygous deletion of the major b1 globin gene were studied at 2 and 8 months. Mice Hbb(th/3+), characterized by the heterozygous deletion of b1 and b2 globin genes were studied at 4 and 10 months. Hematologic data were obtained and iron overload estimated by Perls' staining of the liver. Expression of liver hepcidin, Tfr2, Hjv, Fpn and Hfe RNA was assessed by real-time polymerase chain reaction. Levels of serum cytokines (interleukin-6, IL-1beta, IL-10, granulocyte-macrophage colony-stimulating factor) levels were assayed by enzyme-linked immunosorbent assay., Results: Hemoglobin, hematocrit and mean corpuscular volume were significantly reduced in both beta-thalassemia models, more significantly in Hbb(th/3+), which have the greater, age-dependent, iron overload. Hepcidin RNA was not increased despite iron overload in both strains. Fpn RNA was increased and Tfr2 was decreased in older animals. Inflammatory cytokine levels were striking variable and unrelated to hepcidin levels., Interpretation and Conclusions: Although anemia is reported to inhibit hepcidin expression, normal hepcidin synthesis was maintained in both thalassemic models studied. However, hepcidin levels were inappropriate for the body iron, especially in Hbb(th/3+) 10-month-old animals. As we previously reported in wild type mice after parenteral iron overload, Tfr2 is reduced and Fpn RNA increased in thalassemic mice. Inflammatory cytokines did not play a major role in increasing hepcidin levels or in modifying iron homeostasis in this study.

A flow cytometric approach to minimal residual disease (MRD) monitoring useful in childhood B-lineage acute lymphoblastic leukemia (ALL) is discussed here in the context of ALL in adults. Of 64 leukemia samples analyzed, 95.3% had at least one abnormal phenotype (57.3% had two or more) as compared to physiologic B-cell precursors in adult bone marrow. The method was sensitive enough to detect one leukemic cell among 10,000 normal cells in 16/19 experiments (84.2%). Blast phenotypes were stable in culture and at relapse, and were useful for MRD monitoring in patients. Marker combinations for childhood ALL are also applicable to adult cases.

The association of lymphoid neoplasms and antiphospolipid antibodies (APA), with or without thromboembolic complications, has been reported in several cases. We describe one case of B-cell non-Hodgkinís lymphoma (NHL) in which the combination of rituximab with standard chemotherapy led to the complete remission of a severe hypercoagulable state associated with APA.

Background and Objectives: Somatic hypermutation of the BCL6 gene and its expression in lymphoma represent specific markers for B-cell transit through the germinal center. Thus, analysis of BCL6 may aid in clarifying the relationship between primary mediastinal B-cell lymphoma (PMBL) and other non-thymic diffuse large cell lymphomas (DLCL)., Design and Methods: Twenty-four PMBL were analyzed for BCL6 status, including first intron mutations, by quantitative reverse transcription polymerase chain reaction (RT-PCR), and immunohistochemistry. We also performed a meta-analysis of reported BCL6 mutations in PMBL (n=141), DLCL (n=233), and follicular lymphoma (n=120)., Results: Thirteen PMBL (54%) showed hypermutation of BCL6. All cases showed bcl6 mRNA and immunohistochemical expression. Meta-analysis demonstrated that the preferentially altered sequence motifs of BCL6 in PMBL were TA (p=0.002) and AT (p=0.0008) dinucleotides and TAT trinucleotides (p=0.001). GC and RGYW/WRCY motifs were a target in DLCL and FL but not in PMBL. Moreover, the DNA stretch spanning nucleotides 150-270 was highly targeted only in PMBL., Interpretation and Conclusions: The consistent expression of bcl6 protein and occurrence of hypermutation indicate that PMBL should be considered of germinal center origin. The fact that the hypermutation sites and mutational spectrum of BCL6 in PMBL differ from those found in FL and DLCL might suggest that the maturation block of the transforming cells differs among these tumor types, and that the characteristic mutational pattern is present before neoplastic transformation. Thus, our findings strengthen the hypothesis that PMBL originate from an already defined sub-population of B-cells, which are different from those leading to either DLCL or FL.

Background and Objectives: There are data consistent with an association between idiopathic thrombocytopenic purpura (ITP) and Helicobacter pylori (HP) infection. In addition, a significant increase of platelet count following HP eradication has been reported in a proportion of ITP patients. We describe here our experience on the efficacy of anti-HP treatment in ITP patients., Design and Methods: Between December 1998 and May 2001 sixteen adult patients with ITP and documented HP infection were treated with standard antibiotic therapy for HP eradication (amoxicillin and clarithromycin plus pantoprazole combination). Of these patients, 7 had untreated ITP with mild/moderate thrombocytopenia (median platelet count 70x10(9)/L, range 41-91), 5 had relapsed following a previous steroid treatment (median platelet count 39x10(9)/L, range 30-90) and 4 were refractory to steroids (median platelet count 18.5x10(9)/L, range 9-30)., Results: An improvement of platelet count was observed in 11/15 patients (73.3%) who achieved HP eradication. The difference between the mean platelet count SD before and after HP eradication was statistically significant (51.6 28.2x10(9)/L vs. 143.3 131.1x10(9)/L; p=0.01). Complete or partial responses were obtained in 11/16 treated patients (68.7%). This result still persisted after a median follow-up of 11.7 months., Interpretation and Conclusions: Our data confirm the efficacy of Helicobacter pylori eradication in increasing platelet count in adult ITP patients.

Background and Objective: Cohen syndrome is a multiple congenital anomalies-mental retardation syndrome associated with granulocytopenia. To date, the mechanisms involved in causing the neutropenia are unknown. In order to get insight into the mechanisms of neutropenia, we studied both the bone marrow and the functional properties of neutrophils obtained from peripheral blood (PB) or skin window (SW) exudate of a patient affected by Cohen syndrome., Design and Methods: Assays of superoxide anion release (as reduction of cytochrome C) and cell adhesion (quantified by measuring membrane acid phosphatase) were carried out according to a microplate method whereby both parameters can be evaluated (Bellavite et al., 1992). Neutrophil surface integrins and CD62L (selectin) were evaluated by flow cytometry., Results: Bone marrow did not show relevant morphological abnormalities in either erythroid or myeloid precursors. Cohen neutrophils exhibited a greater adhesive capability than control leukocytes in all the conditions studied (PB or SW, unstimulated or agonist-stimulated leukocytes). Cytofluorometric evaluation of neutrophil beta 2 integrin (CD11b) and selectin (CD62L) showed a lower mean fluorescence intensity and a lower percentage of fluorescence conjugate monoclonal Ab-positive cells in the patient than in control subjects. Moreover, a double population of neutrophils, with different affinities to the specific monoclonal antibody anti-CD11b, was observed in the patient. Superoxide anion release, expression and distribution of fluorescence conjugate MoAb anti-human CD11a were normal., Interpretation and Conclusions: Neutrophil adhesive capability was greatly increased in a case of Cohen syndrome. Cytofluorimetric expression of CD11b and CD62L molecules was consistent with a generalized neutrophil activation in vivo.

Intestinal absorption of non-heme food iron may be inhibited by tea, which, on the contrary, does not exert any appreciable effect on heme iron assimilation. Therefore, while an iron-deficiency anemia cannot develop in non-vegetarian subjects as a consequence of tea consumption only, it is possible that tea could inhibit the therapeutic effect of oral iron drugs, which are usually non-hemic ferrous salts, in iron-deficient subjects. This view is supported by the case we describe here, a young woman affected by hypermenorrhea and iron-deficiency anemia, who did not respond to oral iron treatment until she stopped her long-established habit of consuming large quantities of tea. We also believe that oral iron drugs should never be taken together with a cup of tea; therefore we think it useful to advise our iron-deficient patients clearly not to combine tea with the oral consumption of non-hemic ferrous salts.

Folates are essential molecules for cell life and, not surprisingly, their transport in biological fluids and their transfer to cells are finely regulated. Folate binding proteins play a major role in this regulation. This paper will review our knowledge on these proteins and examine the most recent advances in this field.

An accurate determination of the total amount and distribution of body iron stores is essential for prognostic purposes and to evaluate the efficacy of chelation therapy. In the clinical setting, a rough estimate of the total body iron burden may be obtained in patients with transfusion-dependent anemias by calculating the amount of blood administered plus the amount absorbed by the gastrointestinal route, which is influenced by the level of Hb and by bone marrow activity. An increase in serum iron and a decrease in total iron binding capacity are early indicators of iron overload, but their sensitivity and specificity are not very high. In normal individuals, serum ferritin correlates well with iron stores, as measured by phlebotomy, and with directly measured liver iron. However, plasma ferritin, being an acute phase reactant, is increased in cases of chronic disease, disseminated malignancy, or inflammatory disorders. Non-transferrin bound iron, i.e. iron that circulates in plasma unbound to transferrin, is potentially toxic since it is capable of taking part in free radical-mediated reactions that result in irreversible tissue damage. This iron can be measured with a HPLC based assay. At present the most accurate way of estimating the iron burden is by direct measurement of iron concentration in tissues. The liver is the most accessible. The measurement is done by atomic absorption spectrometry on ashed or lyophilized samples obtained by needle biopsy, and correlates well with the total amount of blood transfused and with the extent of hepatic fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Peripheral neuropathy of the limbs has so far been observed in very few patients with localized Castleman's disease, generally of the plasma-cell type. In the present case report, of a plasmacellular type localized within the mesenterium, a 25-year-old woman exhibited a clinical picture of right trigeminal neuropathy (together with more common constitutional symptoms and laboratory findings), which promptly disappeared after surgical removal of the mesenteric mass. To our knowledge, a similar impairment of cranial nerves, and specifically of the trigeminal, has never been reported in patients with the localized form of Castleman's disease.