Short lingual frenulum: From diagnosis to laser and speech-language therapy.

AIM: To evaluate the effects of tongue frenulectomy performed with two therapeutic approaches: Laser frenulectomy and combined laser and speech-language therapy. MATERIALS AND METHODS: The study involved 180 patients (90 males and 90 females) aged between 6 and 12 years. After examination and data collection, the patients were stratified according to three degrees of severity: mild, moderate and severe. After treatment, the test group (laser frenulectomy and combined laser and speech-language therapy) was compared with the control group (laser frenulectomy) in the pre-surgical phase, at one week, 1 month, 3 months, 6 months and 12 months after surgery. RESULTS: Statistical analysis showed statistically significant differences between the pre-surgical and post-surgical values at 3 months, 6 months and 12 months after surgery (p<0,05). CONCLUSIONS: It is essential to establish diagnosis criteria to which the clinician should refer in order to decide the treatment plan. This study shows that combined laser and speech-language therapy leads to better results than the resection treatment of the frenulum with laser technique alone.

Diagnostic role and prognostic significance of a simplified immunophenotypic classification of mature B cell chronic lymphoid leukemias.

We verified the diagnostic and prognostic role of a simplified immunophenotypic classification (IC) in a series of 258 patients (M/F: 1.4; median age: 64 years; median follow-up: 64 months; 75 deaths) with mature B cell lymphoid leukemias (MBC-LL) for whom no histopathological diagnosis was available because of minimal or no lymph node involvement. The IC was based on the reactivity of three pivotal immunophenotypic markers: CD5, CD23 and SIg intensity. On the basis of different expression patterns, we identified four diagnostic clusters (C) characterized by distinct clinico-biological features and different prognoses: C1 (149 patients) identified most classical B cell chronic lymphocytic leukemias (CLL-type cluster; SIg(dim)/CD5+/CD23+); C2, 38 patients whose clinico-hematological characteristics were intermediate between C1 and C3 (CLL-variant cluster; SIg(bright)/CD5+/CD23+/-or SIg(dim)/CD5-/-/CD23 indifferent); C3 (16 patients) most situations consistent with mantle cell lymphoma in leukemic phase (MCL-type cluster; SIg(bright)/CD5+/CD23-); and C4, 55 cases, most of whom were consistent with leukemic phase lymphoplasmacytic/splenic marginal zone lymphomas (LP/S-type cluster; SIg(bright)/CD5-/+/CD23 indifferent). At univariate survival analysis, prognosis worsened from C1 to C4, C2 and C3 (P = 0.0001), and this was maintained at multivariate analysis (P = 0.006), together with CD11c expression (P = 0.0043), age at diagnosis (cut-off 70 years; P = 0.0008) and platelet count (cut-off 140 x 10(9)/l; P = 0.0034). Besides recognising the two well-known situations of classic B-CLL and MCL, our IC identified situations with distinct prognostic and/or clinical behaviors.

Analysis of FGFR3 gene mutations in multiple myeloma patients with t(4;14).

The t(4;14)(p16.3;q32) in multiple myeloma (MM) leads to an apparent deregulation of the FGFR3 and WHSC1/MMSET genes. FGFR3 mutations, known to be associated with genetic skeletal disorders, have also been identified in a few cases of MM (mainly cell lines) with t(4;14). We investigated FGFR3 mutations in a series of 53 MM cases; 11 cases with t(4;14) and FGFR3 overexpression were analysed using reverse transcription polymerase chain reaction, while the remaining cases were studied at DNA level. The Arg248Cys mutation, which is associated with some lethal forms of skeletal disorders, was found in one case with t(4;14). Our results indicate that FGFR3 mutations occur in only a small fraction of MM cases with t(4;14).

Reduction of the homocysteine plasma concentration by intravenously administered folinic acid and vitamin B(12) in uraemic patients on maintenance haemodialysis.

BACKGROUND: Hyperhomocysteinaemia is an independent cardiovascular risk factor which can induce vascular lesions, thus contributing to the early development of atherosclerosis. Low-dose folic acid supplementation reduces the pretreatment homocysteine plasma levels by 25-35%. Recent studies report that higher intravenous or oral administration of the active form of folic acid reduces the homocysteine plasma concentration by nearly 70%. The reduction could also be influenced by the thermolabile variant of methylenetetrahydrofolate reductase (tMTHFR) and by the dialysis modality. METHODS: A cross-sectional clinical study was performed to evaluate the effect of a drug containing folinic acid and vitamin B(12) on the plasma homocysteine concentration and whether this variable could also be influenced by the presence of a genetic variant of the methionine pathway and the use of different dialysis modalities. The plasma homocysteine concentration was measured in 55 patients undergoing haemodialysis, 27 of whom have been treated intravenously for megaloblastic anaemia using a drug containing low concentrations of folinic acid and vitamin B(12) at the end of each dialysis session for 6 months. The presence of tMTHFR was sought by molecular analysis, and the role of the dialysis modality was also investigated. RESULTS: The patients given the folic acid treatment had lower homocysteine plasma levels than those not so treated. The plasma homocysteine concentration was significantly higher in the tMRHFR homozygotes than in the patients with a normal genotype, significantly lower in the treated than in the untreated homozygotes, and significantly higher in the untreated homozygotes than in the untreated subgroup with a normal genotype. The homocysteine level was also significantly lower in the patients who underwent convective haemodialysis than in those who received standard bicarbonate dialysis. CONCLUSIONS: A drug containing low concentrations of folinic acid combined with vitamin B(12) using an intermittent intravenous regimen is effective in reducing the homocysteine plasma concentration in uraemic patients. The homocysteine levels seem also to depend on genotype and dialysis modality.

Hyperhomocysteinemia in myelodysplastic syndromes: specific association with autoimmunity and cardiovascular disease.

Hyperhomocysteinemia (HH) has been associated with cardiovascular and autoimmune diseases and oxidative cell damage. Myelodysplastic syndromes (MDS) are associated with autoimmunity (AI) and increased oxidative stress. We tested the association of HH and oxidative stress in 33 MDS patients, by measuring plasma homocysteine and malondialdehyde (MDA). HH was found in 42% of cases, (4/5) cases with associated cardiovascular events (CVE)(80%), and 9/15 cases with associated AI (60%). Thus in MDS, HH was significantly associated with AI/CVE (chi(2) : p=0.0011), and this association seems to be specific, as demonstrated by the comparison of MDS presenting AI/CVE with the ischemic cardiopathy/rheumatoid arthritis control group (13/20, 65% vs 19/69, 27%; chi(2) : p=0.0021). The levels of MDA indicated increased oxidative stress. Our data may suggest that in a subset of MDS, HH may simultaneously contribute to bone marrow myelodysplasia, CVE and AI pathogenesis, possibly through oxidative cell damage.

Homocysteine, vitamin B12, serum and erythrocyte folate in peritoneal dialysis patients.

Plasma homocysteine (tHcy) is an important risk factor for atherosclerosis in dialysis patients. Few data were reported on the prevalence and severity of hyperhomocysteinemia in peritoneal dialysis (PD) patients. In addition, little attention was paid to the search of factors possibly involved in the pathogenesis of hyperhomocysteinemia in these patients. A cross-sectional study was performed in 107 stable PD patients. None of them was given folate or vitamin B12 supplementation before or during the study. Plasma tHcy, serum vitamin B12, serum and erythrocyte folate were measured by immunoenzymatic methods. Genetic analysis of the methylentetrahydrofolate-reductase thermolabile mutation (tMTHFR) was performed in 61 patients. 97% of patients had tHcy levels higher than normal. tHcy was not different between men and women, patients with or without malnutrition, with or without clinically evident atherosclerotic vasculopathy, with or without anemia. tHcy levels were significantly higher in homozygotes for the tMTHFR mutation than in patients carrying the wild type form. Significant univariate correlation was found between hyperhomocysteinemia and time since the start of dialysis, serum and erythrocyte folate and vitamin B12. The best fitted model equation was log tHcy = 108.53 + 0.1606 (duration of dialysis) -1.1053 (s-F) -0.7980 (age) 0.0215 (vitamin B12). Our results agree with those reported by other authors in hemodialysis patients. Despite the large number of PD patients with normal serum vitamin B12 and folate status, the relation between tHcy and vitamin B12 or folate suggests that the supplementation of these vitamins could be useful irrespective of their serum levels, especially in younger patients or in those treated for a long period of time with peritoneal dialysis.

Factors predicting response to splenectomy in adult patients with idiopathic thrombocytopenic purpura.

BACKGROUND AND OBJECTIVES: Splenectomy is the treatment of choice in the majority of patients affected by idiopathic thrombocytopenic purpura refractory to corticosteroid therapy, but it is not free from early and late complications. As the available literature does not seem to contain any precise indications concerning possible factors predicting the response to splenectomy, the aim of this retrospective study of 65 splenectomized patients was to attempt to identify potentially predictive clinical or laboratory parameters. DESIGN AND METHODS: For the purposes of statistical analysis, the patients were divided into two groups: the first included those with a complete (platelets > 100x10(9)/L) or partial response (platelets 50-100 x10(9)/L) to splenectomy; the second, the non-responders (platelets < 50x10(9)/L). The non-parametric tests were based on the Kruskal-Wallis method for independent samples, and the independent samples were compared using the Chi-square test according to Pearson. RESULTS: Univariate analysis did not reveal any significant correlation between successful splenectomy and age, sex, platelet count at diagnosis, anti-platelets antibody positivity, the site of platelet sequestration, the time between diagnosis and surgery, or the response to high intravenous immunoglobulin doses. However, the probability of success was greater in the patients with a complete or partial pre-operative response to steroid therapy (p<0.05). INTERPRETATION AND CONCLUSIONS: The factor most frequently associated with the success of splenectomy is the site of autologous platelet sequestration. Our study did not identify any clinical or laboratory parameter clearly predictive of post-splenectomy cure other than a transient response to steroid treatment. This finding needs further confirmation in larger patient populations.

Cytokines and hemostasis.

BACKGROUND AND OBJECTIVES: Cytokines are low molecular weight polypeptides that act as pleiotropic mediators of inflammation and may contribute significantly to regulation of hemostatic balance in both physiologic and pathologic conditions. The purpose of this review is to underline the most significant progresses recently achieved in this rapidly growing area. DESIGN AND METHODS: The authors have been involved both at home and abroad in experimental and clinical research in this field for years and have contributed original papers in peer-reviewed journals. In addition, the material examined in the present review includes articles published in journals covered by the Science Citation Index and Medline. RESULTS: Tissue factor, a transmembrane glycoprotein that serves as a surface receptor for coagulation factor VIIa, plays a key role in the initiation of coagulation processes. Very little, if any, tissue factor activity is detectable in normal conditions on the cell surface of monocytes and endothelial cells. However, upon proper stimulation by a number of agents such activity may be expressed in these cells, which can then contribute significantly to clotting activation. Pro-inflammatory cytokines (IL-1, IL-6 and TNF) are effective inducers of tissue factor upregulation and may trigger endothelial cells to change their antithrombotic properties into a procoagulant, clot-promoting state. Indeed, much experimental and clinical evidence has been accumulated to suggest that cytokines play a key role in the pathophysiology of hemostatic abnormalities in different disease states. These include, inter alia, the coagulopathy observed during septicemia, the veno-occlusive disease of the liver after bone marrow transplantation, the prothrombotic state associated with atherosclerotic vessels, the occurrence of deep venous thrombosis after major abdominal surgery and the thrombotic tendency of patients with cancer. Several new antithrombotic strategies based on these new concepts have been attempted in experimental models of thrombosis and also in man. Examples of new possible antithrombotic agents are the tissue factor pathway inhibitor, Fab fragments of monoclonal antibodies directed against factor VII or factor VIIa, mutant forms of biologically inactive tissue factor and inhibition of cytokines involved in the regulation of tissue factor expression. Many of these studies have produced positive or interesting results, although more must be learned before the appropriate drug and the adequate dose are defined in the different clinical situations. CONCLUSIONS: Pro-inflammatory cytokines (IL-1, IL-6 and TNF) play a key role in tissue factor expression on monocytes and on endothelial cells and contribute significantly to regulation of hemostatic balance in physiologic and pathologic conditions. This effect is of great interest from both speculative and practical viewpoints.

Detection of t(4;14)(p16.3;q32) chromosomal translocation in multiple myeloma by reverse transcription-polymerase chain reaction analysis of IGH-MMSET fusion transcripts.

We and others have recently identified a novel recurring t(4;14)(p16.3; q32) translocation in multiple myeloma (MM) that leads to an apparent deregulation of the FGFR3 and WHSC1/MMSET genes. Because the presence of IGH-MMSET hybrid transcripts has been found in MM cell lines with t(4;14), they may represent a specific tumor-associated marker in MM. In this study, we developed a reverse transcription-PCR (RTPCR) assay for detecting chimeric transcripts from all of the 4p16.3 breakpoints identified thus far, and we used it to investigate a representative panel of 53 MM patients and 16 patients with monoclonal gammopathy of uncertain significance; in addition, t(4;14) was investigated in all of the MM patients by means of two-color fluorescence in situ hybridization. IGH-MMSET transcripts were found in 11 of the 53 (20%) MM cases and 1 of 16 (6%) cases of monoclonal gammopathy of uncertain significance. There was complete concordance between the RT-PCR and fluorescence in situ hybridization analyses of the MM cases. The results of this study indicate that RT-PCR is a sensitive and reliable method of detecting t(4;14) and suggest that it may be useful for monitoring the disease in a significant proportion of patients.

Amifostine, a reactive oxigen species scavenger with radiation- and chemo-protective properties, inhibits in vitro platelet activation induced by ADP, collagen or PAF.

BACKGROUND AND OBJECTIVES: Reactive oxygen species (ROS) generation has been suggested to represent an important regulatory mechanism of platelet reactivity in both physiologic and pathologic conditions; consistent with this hypothesis is the observation that free-radical scavengers may inhibit platelet activation, thus contributing to the regulation of their reactivity. The purpose of the present study is to study the in vitro effects of amifostine (WR-2721, ethyol ), a selective cytoprotective agent for normal tissues against the toxicities of chemotherapy and radiation, on platelet activation induced by the physiologic agonists ADP, collagen and PAF. DESIGN AND METHODS: The effect of amifostine, added to the experimental system at final concentrations ranging from 10(-7) M to 10(-5) M, was studied on platelet aggregation induced by the following physiologic agonists at the given concentrations: ADP (1 microM), collagen (2 microg/mL), and PAF (0.1 microg/mL). Platelet aggregation was investigated using a platelet ionized calcium aggregometer and was expressed as the percentage change in light transmission. Furthermore, thromboxane B((2)) (TxB((2))) levels and nitric oxide (NO) production were determined by radioimmunoassay and by evaluating the total nitrite/nitrate concentration using a commercially available colorimetric kit, respectively, both in the control system and after the addition of amifostine. RESULTS: Amifostine inhibited both platelet aggregation and TxB((2)) production induced by ADP, collagen and PAF, in a dose-dependent manner. Amifostine proved to be an effective inhibitor of platelet function and the effect was more pronounced if platelets were stimulated with ADP, intermediate when collagen was the chosen agonist, and less evident, though present, when PAF was used. Platelets stimulated with ADP, collagen or PAF produced significant amounts of NO over the baseline. When amifostine was added at a final concentration of 5 microM, it significantly increased ADP, collagen and PAF-induced NO production, which suggests that NO release by activated platelets was involved in the inhibitory effect of amifostine. INTERPRETATION AND CONCLUSIONS: Amifostine proved to be an effective inhibitor of platelet activation induced in vitro by physiologic inducers. This previously unrecognized effect was more evident with the weak agonist ADP and was related to reduced NO consumption by free radicals generated during platelet activation. Amifostine proved to be not only a powerful cytoprotectant, but, more generally, a therapeutic agent endowed with several relevant, though largely unknown, biological effects. Finally, our data once again support the concept that oxidative balance is of crucial importance in regulating platelet reactivity in both health and disease.

Immunohistochemical analysis of cyclin D1 shows deregulated expression in multiple myeloma with the t(11;14).

The t(11;14)(q13;q32) chromosomal translocation, the hallmark of mantle cell lymphoma (MCL), is recurrently found in multiple myelomas (MM) by means of conventional cytogenetics. Unlike MCL, recent molecular studies of MM-derived cell lines with t(11;14) have indicated that the breakpoints are highly dispersed over the 11q13 region; however, the fact that cyclin D1 is generally overexpressed in these cell lines suggests that this gene is the target of the translocation. To evaluate further the involvement of cyclin D1 in MM, we used immunohistochemistry and fluorescence in situ hybridization to investigate cyclin D1 expression and the presence of chromosome 11 abnormalities in a representative panel of 48 MM patients (40 at diagnosis and 8 at relapse). Cyclin D1 overexpression occurred in 12/48 (25%) of cases; combined immunohistochemistry and fluorescence in situ hybridization analyses in 39 patients showed cyclin D1 positivity in all of the cases (7/7) bearing the t(11;14), in two of the 13 cases with trisomy 11, and in one of the 19 cases with no apparent abnormalities of chromosome 11. Our data indicate that the t(11;14) translocation in MM leads to cyclin D1 overexpression and that immunohistochemical analysis may represent a reliable means of identifying this lesion in MM.

Homocysteine, vitamin B12, and serum and erythrocyte folate in peritoneal dialysis and hemodialysis patients.

BACKGROUND: Plasma homocysteine (Hcy) is an independent risk factor for cardiovascular disease. High levels of plasma Hcy have been observed in end-stage renal disease patients. Few studies have compared peritoneal dialysis (PD) and hemodialysis (HD) patients and few data are available on erythrocyte folate (ery-F) levels in dialysis patients. OBJECTIVES: To evaluate plasma Hcy concentrations, vitamin B12 (B12), and folate status in dialysis patients; to analyze the possible causes of high Hcy levels; to follow up changes in folate and B12 concentrations after 6 months. DESIGN: A cross-sectional observational study. SETTING: Nephrology division and laboratory of hematology in a university and clinical research hospital. PATIENTS: The study included 82 patients treated with PD for 37 + 37 months and 70 patients treated with HD for 136 + 95 months. LABORATORY METHODS: Plasma Hcy was measured by the immunoenzymatic IMx Hcy FPIA method (Abbott Laboratories, Diagnostic Division, Abbott Park, IL, U.S.A.), serum folate (s-F) and ery-F by the Stratus folate fluorometric enzyme-linked assay, and B12 by the Stratus vitamin B12 fluorometric enzyme-linked assay (DADE-Behring, Newark, DE, U.S.A.). RESULTS: Ninety-six percent of PD and 97% of HD patients had Hcy levels above the cutoff (13.5 micromol/L). Homocysteine level was higher in HD than in PD patients, while the prevalence of hyperhomocysteinemia was similar with the two techniques. Erythrocyte folate was significantly higher in PD (1333 +/- 519 pmol/L) than in HD (1049 +/-511 pmol/L, p < 0.01). Statistically significant correlations were observed between Hcy and B12, s-F, ery-F, and dialysis duration. Multivariate analysis showed a strong correlation between s-F and Hcy. After 6 months there were no differences in Hcy, B12, s-F, and ery-F levels. CONCLUSIONS: Plasma Hcy levels were high in more than 95% of our dialysis patients, with no relation to the type of dialysis. Vitamin B12 and folate were normal in the majority of our patients. However, serum folate was the major determinant of Hcy levels. Such a relation between Hcy and folate suggests that levels of folate within the reference interval are inadequate for dialysis patients.

BCL10 gene mutations rarely occur in lymphoid malignancies.

BCL10, a gene involved in apoptosis signalling, has recently been identified through the cloning of chromosomal breakpoints in extranodal (MALT-type) marginal zone lymphomas carrying the t(1;14)(p22;q32) translocation. BCL10 was also found mutated in these cases as well as in other types of lymphoid and solid tumors, suggesting that its inactivation may play an important pathogenetic role; however, this has been questioned by recent studies showing a lack of somatic mutations in human cancers. We report the mutation analysis of exons 1-3 of the BCL10 gene in DNAs from 228 cases of lymphoid malignancies (30 B cell chronic lymphocytic leukemias, 123 B and 45 T non-Hodgkin's lymphomas and 30 multiple myelomas). Somatic mutations were detected in four cases (approximately 2%): one small lymphocytic, one follicular and two diffuse large cell lymphomas. The mutations were all within exon 3 and have not been previously reported. Our data suggest that BCL10 mutations may play only a limited role in the pathogenesis of lymphoid neoplasms.

Efficacy of N-acetylcysteine and all-trans retinoic acid in restoring in vitro effective hemopoiesis in myelodysplastic syndromes.

We evaluated the in vitro effect on clonogenic potential (CFU-GM) and apoptosis in myelodysplastic syndromes (MDS) progenitors of an anti-oxidant (N-acetylcysteine, NAC) and/or a differentiating (all-trans retinoic acid, ATRA) agent. NAC significantly reduced apoptosis, both NAC and ATRA induced an increase in CFU-GM, but NAC seemed to be particularly effective in the high risk (HR) MDS. NAC + ATRA conferred a significant advantage in terms of CFU-GM with respect to NAC and ATRA alone. Tumor Necrosis Factor-alpha (TNF-alpha) levels decreased after incubation with NAC in the MDS samples. This study shows that ineffective hemopoiesis in MDS could benefit from both NAC and ATRA, suggesting that anti-oxidant treatment may play a role in guaranteeing MDS cell survival, predisposing them towards differentiation.

OPP-EBV-CAD regimen as salvage treatment in advanced refractory or resistant multiple myeloma.

With the aim of developing an effective therapy for heavily pretreated refractory MM outpatients, we evaluated the OPPEBVCAD regimen, a Hodgkin's disease-derived protocol that includes many drugs effective in MM administered in a sequential schedule. Twenty-two pts aged 42-72 years, with symptomatic highly-pretreated refractory (18 cases), or primary resistant MM (four cases. including two pts with plasma cell leukemia-PCL) received this therapy every 28 days (2-4 cycles, followed by a maintenance program). Therapeutic response (Chronic Leukemia-Myeloma Task Force criteria) and performance status (PS) and pain (W.H.O.) were evaluated. All of the pts were evaluable for response. There were 9 (40%) objective responses (OR: stabilization of blood counts and bone lesions, serum calcium normalization, 50% or more reduction in the concentration of serum monoclonal component (MC), 90% reduction in Bence-Jones proteinuria), 8 (36%) partial responses (PR: 25-50% reduction in serum MC), 1 no response or stable disease (NR), and 4 (18%) cases of progressive disease (PD). OR plus PR were 77%. Of the 4 primary resistant tumors (2 PCL and 2 MM), 2 achieved PR, 1 OR (a PCL case) and 1 progressed. Median survival was 15 months for responding pts (OR plus PR) and 4.5 months for non-responders (NR plus PD). PS and pain improved in 15 pts and did not change in 9. The most frequent side effects were cytopenias, with one drug related infective death. The OPPEBVCAD regimen proved to be an effective therapy for refractory relapsing or primary resistant MM: in responders (two-thirds of the pts), survival was prolonged by about 10 months. Its efficacy in anthracycline-treated pts, as well as the feasibility of using it on an outpatient basis without any continuous drug infusions, make this regimen a promising third line salvage therapy.

Detection of t(4;14)(p16.3;q32) chromosomal translocation in multiple myeloma by double-color fluorescent in situ hybridization.

Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus at chromosome 14q32 represent a common mechanism of oncogene activation in lymphoid malignancies. In multiple myeloma (MM), variable chromosome partners have been identified by conventional cytogenetics, including the 11q13, 8q24, 18q21, and 6p21 loci. We and others have recently reported a novel, karyotypically undetectable chromosomal translocation t(4;14)(p16. 3;q32) in MM-derived cell lines, as well as in primary tumors. The 4p16.3 breakpoints are relatively scattered and located less than 100 kb centromeric of the fibroblast growth factor receptor 3 (FGFR3) gene or within the recently identified WHSC1 gene, both of which are apparently deregulated by the translocation. To assess the frequency of the t(4;14)(p16.3;q32) translocation in MM, we performed a double-color fluorescent in situ hybridization (FISH) analysis of interphase nuclei with differently labeled probes specific for the IGH locus (a pool of plasmid clones specific for the IGH constant regions) or 4p16.3 (yeast artificial chromosome (YAC) 764-H1 spanning the region involved in breakpoints). Thirty MM patients, the MM-derived cell lines KMS-11 and OPM2, and six normal controls were examined. The identification of a t(4;14) translocation, evaluated as the presence of a der(14) chromosome, was based on the colocalization of signals specific for the two probes; a cutoff value of 15% (mean + 3 standard deviation [SD]) derived from the interphase FISH of the normal controls (range, 5% to 11%; mean +/- SD, 8.16 +/- 2.2) was used for the quantification analysis. In interphase FISH, five patients (one in clinical stage I, two in stage II, one in stage III, and a plasma cell leukemia) were found to be positive (approximately 15%). FISH metaphases with split or colocalized signals were detected in only two of the translocated cases and confirmed the pattern found in the interphase nuclei. Furthermore, in three of the five cases with the translocation, FISH analysis with the IGH joining probe (JH) showed the presence of the reciprocal product of the translocation [der(4) chromosome]. Overall, our study indicates that the t(4;14)(p16. 3;q32) chromosomal translocation is a recurrent event in MM tumors and may contribute towards the detection of this lesion and our understanding of its pathogenetic and clinical implications in MM.

Hypophyseal non-Hodgkin's lymphoma presenting with diabetes insipidus: a case report.

We report the case of a 64 year old male patient with a history of ischemic heart disease who underwent surgery for an abdominal mass. The histological diagnosis was highly malignant non-Hodgkin's lymphoma. After surgery the patient was admitted to our Department and received 6 courses of chemotherapy according to the COP schedule, followed by radiotherapy to the left upper abdominal region and ipsilateral lung base. The patient achieved partial remission. One month later he began to complain of left axillary lymphadenomegaly, polydipsia and polyuria. A NMR brain scan showed a hypophyseal mass. The patient was treated with DDAVP and chemotherapy with the PRO-MACE protocol; the polyuria and lymphadenomegaly disappeared and the size of the hypophyseal mass reduced markedly. The clinical picture was, therefore, attributed to a hypophyseal localization of the non-Hodgkin's lymphoma, which is a very rare manifestation of lymphomatous spread to the central nervous system. Our case is also interesting because it shows that a favorable outcome can be obtained with chemotherapy, provided that the latter is sufficiently aggressive. This is not necessarily the case with radiotherapy which may also be followed by late and severe neurologic sequelae.

Folate measurements in patients on regular hemodialysis treatment.

Patients on regular hemodialysis treatment may develop megaloblastic anemia caused by folate deficiency, but whether folate supplementation is required is still controversial, particularly during erythropoietin administration. Erythrocyte folate concentration is a better indicator of folate status than serum folate, although the latter is the variable generally measured. We measured serum and erythrocyte folate in blood samples from 112 regular hemodialysis patients (57 men, 55 women, 50 treated with erythropoietin, and 62 not) by Stratus Folate immunoenzymatic assay (Dade). Patients with very low serum (<2.87 ng/mL) but normal erythrocyte folate were reinvestigated 4 months later without receiving folate supplementation meanwhile. Serum folate concentrations were 0.48 to 12.76 ng/mL (median, 3.40) and erythrocyte folate 0.19 to 1.85 microg/mL (median, 0.42). Only 37% serum folate values were in the relevant reference interval compared with 80.2% erythrocyte folate values (3.08 to 17.65 ng/mL and 0.24 to 0.64 microg/mL, respectively). A significant correlation was found between serum and erythrocyte folate concentrations, without clinical relevance caused by the wide scatter around the regression line. Serum and erythrocyte folate did not vary significantly between patients given erythropoietin and those not so treated. The folate status of the 24 patients with very low serum folate was almost unchanged 4 months later. According to the serum folate test, 63% of patients needed folate supplementation, whereas the erythrocyte folate test, a better indicator of folate status, suggested that only 1.8% of patients needed folate supplementation. Erythropoietin therapy appears not to be an indication for standard folate supplementation in hemodialysis patients.

Low plasma stem cell factor levels correlate with in vitro leukemic growth in myelodysplastic syndromes.

We evaluated the effect of SCF on myeloid differentiation by correlating clonogenic potential (as CFU-GM), bone marrow (BM) plasma SCF levels and CD34/c-kit expression in 57 MDS samples. There was a significant correlation between low SCF levels and 'leukemic' in vitro growth, the number of clusters and the colony/cluster ratio. No correlation was found between BM plasma SCF levels, the pattern of growth and CD34+ c-kit+ expression. These data seem to exclude any direct effect of SCF on leukemogenesis, but suggest that low plasma SCF levels may be at least partially responsible for leukemic growth in MDS.