Hb-M "Hyde Park": a de novo mutation, identified by mass spectrometry and DNA analysis.

BACKGROUND. Structural hemoglobinopathies usually are inherited as autosomic dominant traits; de novo mutations are uncommon. Analytical and preparative procedures for the characterization of an abnormal hemoglobin are complex and time-consuming. Mass spectrometer analysis allows a rapid identification of the amino acid substitution. METHODS AND RESULTS. A cyanotic 7-year-old girl was found to have 16% methemoglobin. Laboratory data showed the presence of an abnormal hemoglobin, which was isolated by collecting the abnormal peak from DEAE and globin chains from CM52. The amino acid substitution was rapidly identified by FAB mass spectroscopic analysis, leading to the recognition of HbM Hyde Park. These data were confirmed by molecular analysis (Southern blot and DNA sequencing). Neither the parents nor a sister showed any abnormality; non-paternity was excluded by blood group serology and HLA typing. CONCLUSIONS. This is a case of HbM Hyde-Park arising as a de novo mutation. FAB mass spectroscopic analysis is a rapid and useful analytical method for identifying aminoacid substitution.     

Rapid regression of psoriasis in a coeliac patient after gluten-free diet. A case report and review of the literature

BACKGROUND: Several skin disorders are present in patients affected by coeliac disease (CD) - among them, psoriasis has been described. However, at present the relationship between CD and psoriasis remains controversial since there are few and contrasting data on this topic. METHOD: Here we describe a case of psoriasis in a CD patient not responding to specific therapies for psoriasis. RESULT: The regression of skin lesions after gluten-free diet (GFD) was evident in a short time. CONCLUSION: The present case supports the association between CD and psoriasis and the concept that psoriasis in CD patients can be improved by GFD. Future studies are needed to clarify the possible mechanisms involved in this association.     

High prevalence of hepatitis G virus infection in Hodgkin's disease and B-cell lymphoproliferative disorders: absence of correlation with hepatitis C virus infection

BACKGROUND AND OBJECTIVES: During the last decade an epidemiological association between hepatitis C virus (HCV) and B-cell lymphoproliferative disorders (B-LPD) has been reported; the same association has not been observed for Hodgkin's disease (HD). Hepatitis G virus (HGV) shares genetic and biological features with HCV, thus it might also be involved in lymphomagenesis. DESIGN AND METHODS: The aim of this study was to compare the prevalence of HCV and HGV infection in patients at diagnosis of B-LPD or HD. RESULTS: We tested 227 consecutive untransfused patients (127 with B-LPD and 100 with HD) and 110 healthy controls. The prevalence of HCV infection was significantly higher in B-LPD patients than in controls (17.3% vs. 1.8%, p<0.002 ), whereas it was the same in HD patients as in controls. In contrast, the prevalence of HGV was significantly higher in patients, both those with B-LPD (7.8% vs. 0.9%, p<0.03) and those with HD (13% vs. 0.9%, p<0.002), than in controls. Among the various B-LPD tested, HGV infection was more frequent in B-NHL (11.5%). INTERPRETATION AND CONCLUSIONS: Our data support the hypothesis that HGV infection may play a role in lymphomagenesis and that this role is different and separate from that of HCV.     

Effects of cyclosporine on hematopoietic and immune functions in patients with hypoplastic myelodysplasia: in vitro and in vivo studies

BACKGROUND: Immunosuppression may benefit some patients with hypoplastic myelodysplasia (HMDS) and refractory anemia (RA), but its mechanism of action is still obscure. METHODS: Using flow cytometry, we studied Fas-receptor (Fas-R), Fas-ligand (Fas-L), and interferon-gamma (IFN-gamma) expression in CD34(+) cells and lymphocytes obtained from 11 HMDS and 20 RA patients. In colony assays and long-term cultures, the effects of Fas triggering, IFN-gamma blockade, or cyclosporine(CsA) on the growth of hematopoietic progenitors (colony-forming cells [CFC]) were determined. The effects of CsA at daily doses of 1-3 mg/kg for at least 3 months in HMDS patients were also studied. RESULTS: In basal conditions, committed and immature progenitor cells were found decreased in myelodysplastic (MDS) patients. No significant differences between HMDS and RA patients were detected. IFN-gamma-expressing CD4(+) cells were significantly increased in HMDS patients, whereas intracytoplasmic Fas-L expression was only borderline elevated in CD3(+) MDS cells. Increased numbers of CD34(+) cells expressing Fas-R were found in HMDS and RA patients. CFC and secondary CFC showed higher susceptibility to Fas-L-mediated inhibition and the blockade of IFN-gamma improved marrow primary, but not secondary, CFC growth. CsA added in vitro to patient's lymphocytes significantly decreased the number of IFN-gamma-expressing CD4(+) cells, but not Fas-L production. These effects were associated with increased colony formation. Similar to IFN-gammablockade, production of secondary CFC was not enhanced by CsA. Administration of CsA to patients resulted in prolonged partial hematologic improvement in 8 of 11 HMDS patients. CONCLUSIONS: Increased frequency of IFN-gamma producing CD4(+) cells supports the involvement of lymphocyte-mediated suppression of hematopoiesis in the development of cytopenia in MDS patients. The ability of CsA to decrease in vitro IFN-gamma production may improve hematopoietic function, explaining the beneficial effect of this agent in HMDS patients.     

Estrogen-progestogen induced hematocolpometra following allogeneic stem cell transplant

OBJECTIVES: Gynecological manifestation of chronic graft-versus-host disease (cGVHD) has been invariably described in association with its extensive form. We have also observed it in a patient with the limited cGVHD form. DESIGN: We here describe our experience of gynecological complications in a population of 30 women who were followed up in a single center 12-120 months after allogeneic stem cell transplant (allo-SCT) due to hematological malignancies. All of them manifested premature ovarian failure because of the received treatments. RESULTS: Three out of 14 women who were affected by cGVHD developed hematocolpometra after estrogen + progestogen therapy (EPT) introduction, due to uterine and vaginal dystrophy and synecchiae. Extensive cGVHD, including dermal and mucosal localization, was present in two women while the third had only liver involvement. None of our patients had received radiation therapy or had a posttransplant history of infection. Local application of estrogens consistently improved the gynecological complication. However, vaginal synecchiae tended to relapse when local treatment was interrupted, despite no other apparent evidence of active cGVHD. CONCLUSIONS: All women with cGVHD should undergo gynecological examination before introducing EPT, to avoid unpleasant complication as hematocolpometra. Vaginal and cervical synecchiae should be treated with prolonged local treatments, and temporary use of continuous EPT regimens may be preferable in these women. Moreover, close monitoring by pelvic exam and ultrasonography is advisable during the initial cycles to detect any complication caused by possible intrauterine adhesions undetected during the previous gynecological examination.     

Fine-needle cytology and flow cytometry immunophenotyping and subclassification of non-Hodgkin lymphoma: a critical review of 307 cases with technical suggestions

BACKGROUND: Flow cytometry (FC) is a useful adjunct to fine-needle aspiration cytology (FNC) in evaluating lymphoproliferative disorders. The authors present a critical review of 307 lymph nodal and extra lymph nodal lymphoproliferative disorders that were diagnosed with FNC and FC. METHODS: FC was performed over a 4-year period on 185 palpable and 122 impalpable lymph nodal and extra lymph nodal lymphoproliferative processes under ultrasound or computed tomography guidance. FC was performed using the following fluoresceinated antibodies: CD3, CD4/CD8, CD2/CD7/CD3, CD5/CD10/CD19, CD19/kappa/lambda, FMC7/CD23/CD19, CD38/CD56/CD19, and bcl-2. The series included 15 inadequate, 10 suspicious, and 135 benign reactive hyperplasias (BRHs); 70 primary non-Hodgkin lymphomas (NHLs), and 77 recurrent NHLs (rNHLs). FC/FNC diagnoses of suspicious, NHL, and rNHL were controlled either histologically or clinically or by the interphase fluorescence in situ hybridization demonstration of t(11;14)(q13;q32) in two cases of mantle cell lymphoma. BRHs were controlled by follow-up. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the FC/FNC diagnoses of NHL, rNHL, and BRH were calculated as well as the identification of specific subtypes among the small- and medium-sized cells. RESULTS: Statistical analysis showed 93% sensitivity, 100% specificity, 100% PPV, and 91% NPV in NHL, rNHL, and BRH discrimination. The subclassification of small cell and medium-sized NHLs showed 63% sensitivity, 88% specificity, 95% PPV, and 37% NPV. CONCLUSIONS: FC applied to FNC enhanced the precision of cytologic diagnosis in lymph nodal and extra lymph nodal lymphoproliferative disorders and allowed further subclassification in more than half of the cases, thus avoiding invasive surgical biopsies in many patients.