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D Rafanelli

Publications and source records attributed to D Rafanelli.

43 records · Page 3Linked to original sources

Inadequate erythropoietin production in allogeneic bone marrow transplant patients.

BACKGROUND: There is some evidence that the erythropoietin (Epo) feedback mechanism in response to anemia can be altered in the period immediately following allogeneic bone marrow transplantation (BMT). METHODS: By using a RIA, serum erythropoietin (sEpo) levels were serially measured in 10 BMT patients, from day -10 up to day +30, and the results correlated with the concurrent hemoglobin (Hb) value. Thirty healthy subjects and 15 iron-deficiency anemic patients were used in order to construct our own reference sEpo vs Hb curve. A sEpo value recorded in BMT patients was considered to be inappropriate for any given Hb value when falling below the lower 95% confidence limit of the control curve. RESULTS: Basal sEpo levels were significantly higher than in healthy subjects, and increased further during the BMT procedure, being still higher than controls on day +30. However, Epo production resulted inappropriate for each given Hb value, when compared with the control curve, in 60 out of 67 sEpo determinations performed following graft infusion. The inadequate Epo production was not associated with the development of clinically manifest signs of kidney toxicity. CONCLUSION: These data indicate that Epo production is impaired in the period immediately following BMT and suggest a role for the administration of recombinant human Epo in the short-term management of the anemia associated with BMT.

Anemia↗

Binding of recombinant human 125I-erythropoietin to CFU-E from the spleen of anemic mice.

Erythroid precursors were obtained from the spleen of mice made anemic with phenylhydrazine and used to study the binding of bioactive 125I-rEp to membrane receptors. Kinetic analysis, using splenic cells obtained at different times following the induction of anemia, showed that the maximum binding was reached at day 3, and decreased thereafter; minimal amounts of 125I-rEp were bound to the splenic cells of normal mice. Splenic cells of day 3 anemic mice were fractionated using continuous Percoll density gradients, resulting in a fraction enriched in CFU-E (delta = 1.065-1072 g/ml) which showed the highest 125I-Ep binding on a per cell basis. The amount of 125I-rEp bound was greatly reduced in the densest fractions, which were comprised of maturing erythroblasts. The binding was time- and temperature-dependent, and a significant correlation was found with cell concentration up to 12 X 10(6). The amount of radioactivity specifically bound rose with increasing concentrations of 125I-rEp until a plateau was reached (2.5 nM), whereas non specific binding increased slightly and linearly. The binding of 125I-rEp was susceptible to competitive inhibition by unlabeled rEp, while other hematopoietic growth factors were ineffective. The calculated receptor density on these purified immature erythroid progenitors was 570 molecules with a Kd = 0.5 nM. Overall, these results suggest that the expression of the Ep receptor is reduced with increasing maturation.

Anemia↗

In vivo administration of stem cell factor enhances both proliferation and maturation of murine megakaryocytes.

BACKGROUND: Stem cell factor (SCF) has already been shown to participate in the regulation of erythro- and granulopoiesis. The aim of this study was to define the possible role of SCF in the regulation of megakaryocytopoiesis. METHODS: Stem cell factor activity has been assessed in an in vivo murine model, in which different doses of the factor were either given alone or in association with recombinant human erythropoietin (rhEpo). Mice were sacrificed after a six-day treatment to evaluate the effect of SCF on the number of bone marrow and spleen colony-forming units-megakaryocyte (CFU-Mk), and after a two-day treatment for evaluation of thrombopoietin-like activity. RESULTS: We found that SCF induces a dose-related increase in the number of CFU-Mk in both the bone marrow and spleen of the treated mice, and that in the range of the doses used (from 25 to 200 mg/kg/day) the greatest activity was observed when a dose of 200 mg/kg/day was injected. The effect was enhanced by adding rhEpo to optimal SCF concentrations. SCF also stimulated megakaryocyte maturation as assessed by the megakaryocyte number, the size of acetylcholinesterase-positive cells, 35Sulphur (35S) incorporation into the newly formed platelets. All these parameters were only minimally affected by the addition of rhEpo. CONCLUSIONS: These data suggest that SCF participates in the regulation of megakaryocytopoiesis and that its administration might have a role in the treatment of disorders of platelet production.

Animals↗

Early hemostatic alterations following bone marrow transplantation: a prospective study.

BACKGROUND: The occurrence of coagulation system alterations after bone marrow transplantation (BMT) and their possible role in the pathogenesis of thrombotic complications such as veno-occlusive disease of the liver (VOD) are still a matter of debate. The aim of this study was to evaluate prospectively the alterations in hemostatic balance developing during the early period after BMT (up to day +21) and their relationships (if any) with VOD. PATIENTS AND RESULTS: Twenty-nine patients (15 autologous and 14 allogeneic BMT) entered the study. No patient suffered from thrombotic and/or major hemorrhagic events. Since there were no differences between the two groups of patients with regard to modifications of coagulation parameters, they were considered together for the purposes of the study. We observed a progressive increase from baseline levels of fibrinogen, factor VIII activity (fVIII:C) and von Willebrand factor antigen (vWf), while factor VII antigen (fVIIAg), protein C and plasminogen significantly decreased. The alterations in these test values were maximal on day +14, with a trend towards normal levels one week later. There was no modification of PT, PTT, prothrombin fragment 1 + 2 (F 1 + 2), fXIIC, tPA, PAI-1, D dimer or protein S levels; serum levels of tumor necrosis factor-alpha were also unchanged. CONCLUSIONS: These results suggest that some alterations of the hemostatic system, probably a consequence of endothelial damage, can be detected early after BMT, but their clinical significance remains uncertain due to the lack of a correlation between hemostatic test alterations and the occurrence of thrombotic complications.

Adolescent↗

Oral lesions among HIV-infected hemophiliacs. A study of 54 patients.

BACKGROUND: HIV-infected individuals develop a large variety of oral manifestations. This study was designed to assess the prevalence and types of oral lesions among HIV-positive hemophiliacs. MATERIALS AND METHODS: A study population of 54 hemophiliacs was evaluated from February, 1987 to March, 1992 in order to analyze types, prevalence and relationships to clinical stages of HIV-related oral lesions. Thirty-six (67%) of the group of patients were HIV seropositive. The remaining 18 tested negative to HIV during the observation period. RESULTS: The majority of patients suffered from hemophilia A. One patient was also bisexual and two were also intravenous drug abusers. Analysis of patient stage revealed that half had a CD4+ T-lymphocyte count over 0.5 x 10(9)/L cells, 10 between 0.2 and 0.499 x 10(9)/L and 8 showed a count lower than 200 x 10(9)/L. Oral lesions were recorded in 18 (50%) HIV-seropositive hemophiliacs. No oral lesions were observed among the HIV-seronegative hemophiliacs. Advanced stage of immunosuppression and presence of oral lesions were significantly associated (p = 0.040). Candidiasis was the most common disturbance, followed by hairy leukoplakia. Oral herpes simplex infection, necrotizing gingivitis and facial herpes zoster were found in a small number of patients. Those with oral lesions showed a lower median CD4+ T lymphocyte count (0.209 x 10(9)/L cells; range 0.008 to 0.615) when compared to the ones without oral lesions (median CD4+ count was 0.539 x 10(9)/L cells; range 0.042 to 1.180; p = 0.002). CONCLUSIONS: HIV-seropositive hemophiliacs may develop oral lesions during the course of their disease. Candidiasis and hairy leukoplakia are among the most common manifestations. A careful oral examination should be included in the clinical evaluation of all HIV-infected hemophiliacs.

HIV Seropositivity↗