RESUMEN
The decay path of the Hoyle state in ^{12}C (E_{x}=7.654 MeV) has been studied with the ^{14}N(d,α_{2})^{12}C(7.654) reaction induced at 10.5 MeV. High resolution invariant mass spectroscopy techniques have allowed us to unambiguously disentangle direct and sequential decays of the state passing through the ground state of ^{8}Be. Thanks to the almost total absence of background and the attained resolution, a fully sequential decay contribution to the width of the state has been observed. The direct decay width is negligible, with an upper limit of 0.043% (95% C.L.). The precision of this result is about a factor 5 higher than previous studies. This has significant implications on nuclear structure, as it provides constraints to 3α cluster model calculations, where higher precision limits are needed.
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A detailed knowledge of the decay properties of the so called Hoyle state in the 12 C nucleus ( E x = 7.654 MeV, 0 + ) is required to calculate the rate at which carbon is forged in typical red-giant stars. This paper reports on a new almost background-free measurement of the radiative decay branching ratio of the Hoyle state using advanced charged particle coincidence techniques. The exploitation, for the first time in a similar experiment, of a bidimensional map of the coincidence efficiency allows to reach an unitary value and, consequently, to strongly reduce sources of systematic uncertainties. The present results suggest a value of the radiative branching ratio of Γ rad / Γ tot = 4.4 ( 6 ) · 10 - 4 . This finding helps to resolve the tension between recent data published in the literature.
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Distributions of the largest fragment charge, Zmax, in multifragmentation reactions around the Fermi energy can be decomposed into a sum of a Gaussian and a Gumbel distribution, whereas at much higher or lower energies one or the other distribution is asymptotically dominant. We demonstrate the same generic behavior for the largest cluster size in critical aggregation models for small systems, in or out of equilibrium, around the critical point. By analogy with the time-dependent irreversible aggregation model, we infer that Zmax distributions are characteristic of the multifragmentation time scale, which is largely determined by the onset of radial expansion in this energy range.
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Fragment partitions of fragmenting hot nuclei produced in central and semiperipheral collisions have been compared in the excitation energy region 4-10 MeV per nucleon where radial collective expansion takes place. It is shown that, for a given total excitation energy per nucleon, the amount of radial collective energy fixes the mean fragment multiplicity. It is also shown that, at a given total excitation energy per nucleon, the different properties of fragment partitions are completely determined by the reduced fragment multiplicity (i.e., normalized to the source size). Freeze-out volumes seem to play a role in the scalings observed.
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Lanthanum is a third-generation, non-calcium and non-aluminium-based phosphate binder indicated for the treatment of hyperphosphatemia in stage 5 chronic kidney disease. The drug is well tolerated, with gastrointestinal complications as its main side effect. Recently, some case reports have described the typical X-ray features of this compound. We report another case of the radiopaque appearance of lanthanum carbonate, which underlines that clinicians need to be aware that its ingestion may cause opacifications in the colon.
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Colon/diagnóstico por imagen , Lantano , Diálisis Renal , Humanos , Masculino , Persona de Mediana Edad , RadiografíaRESUMEN
An increased cytokine production, correlated with long term complications of uremic disease, has been described during hemodialysis. To identify possible differences in the cytokine release of differently sterilized membranes, we enrolled six uremic patients on chronic hemodialysis. The patients underwent dialysis with ETO-sterilized low-flux polysulphone membranes (F6, Fresenius AG) for at least three months (A1), they were then switched to steam-sterilized polysulphone membranes (F6-HPS Fresenius AG) and further evaluations after one (B1) and two months (B2) were carried out. A final evaluation (A2) was made one month after switching back to F6 dialyzers. At each time period, samples were drawn to measure IL-1beta released by cultured mononuclear cells (MN). Moreover, dialysate samples were collected to test endotoxin levels. C3a and C5a levels were assessed at 0, 5, 15 and 60 min from starting hemodialysis. Anti-ETO IgE levels were also assayed at A1, B1 and A2. The LAL test revealed a good quality dialysate. The mean pre-dialysis IL-1beta levels were 215 pg/million cells at A1; falling to 49 at B1, and 54 at B2 (p<0.01); there was then a sharp rebound at A2: 284, p<0.01. Post-dialysis levels followed the same pattern. No correlation between the dialysate endotoxin level and cytokine release was found. Complement activation did not change and in all the phases of the study no anti-ETO IgE was detected in any of the subjects. Our data suggest that the steam sterilized polysulphone membrane induces a lower cytokine release than the ETO sterilized membrane, although the mechanism by which it does so remains to be clarified.
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Materiales Biocompatibles , Interleucina-1/sangre , Leucocitos Mononucleares/metabolismo , Membranas Artificiales , Diálisis Renal/métodos , Adulto , Anciano , Activación de Complemento/efectos de los fármacos , Complemento C3a/análisis , Complemento C5a/análisis , Óxido de Etileno , Humanos , Persona de Mediana Edad , Polímeros , Diálisis Renal/instrumentación , Vapor , Esterilización , Sulfonas , Uremia/complicaciones , Uremia/terapiaRESUMEN
Ethylene oxide (ETO) is presently the most commonly used sterilization method for medical devices. Although alternative sterilization modes such as steam sterilization have been suggested, the effect of steam on dialysis-induced cytokine release is unknown. We enrolled 9 patients on chronic hemodialysis and evaluated at different intervals IL-1beta production while treated with ETO (NC 1785-Bellco) and steam sterilized NC 1785S-Bellco) Synthetically Modified Cellulose (SMC). A basal test during treatment with NC 1785 was performed (A); the same test was set up 4 weeks after treatment with NC 1785S (B) and, lastly, 4 weeks after returning to NC 1785 (C). Peripheral blood mononuclear cells (PBMC) were purified before and after the dialysis session, were isolated on a Ficoll/Hypaque gradient and incubated for 24 h. Spontaneous IL-1beta release was evaluated in the supernatant and in the lysate. In A, IL-1beta levels were (in pg/ml/10(6) cells, in supematant and lysate, respectively): 5.8 +/- 4.8 and 7.6+/-5.2 in pre-HD and 4.68 +/- 3.6 and 9.7 +/- 6.65 in post-HD. These levels showed a clear reduction in B: 2.5 +/- 2.2 and 4.4 +/- 3.1 in pre-HD, and 4.35+/- 6.6 and 7.52 +/- 7.22 in post-HD. In the C test, 4 weeks after the return to the ETO membrane, IL-1beta levels remained unchanged: 2.9 +/- 1.8 and 4.5 +/- 3.1 in pre-HD; and 2.6 +/- 3 and 5.7 +/- 6.6 in post-HD. Statistical analysis showed significant changes in the pre-HD levels both in supematant (p < 0.04) and in lysate (p < 0.04). Steam sterilization of SMC induced a lower spontaneous IL-1beta release, but this effect was not statistically significant due to the large inter-individual variation. Hence, contrary to claims of better biocompatibility, steam sterilization does not result in a reduced production of pro-inflammatory IL-1beta.
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Interleucina-1/análisis , Diálisis Renal , Vapor , Esterilización/métodos , Materiales Biocompatibles , Células Cultivadas , Celulosa/química , Desinfectantes/uso terapéutico , Escherichia coli/química , Óxido de Etileno/uso terapéutico , Humanos , Prueba de Limulus , Membranas Artificiales , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/análisisRESUMEN
BACKGROUND: It has been suggested that calcitriol (C) could improve anemia in chronic renal failure. However it remains debatable whether vitamin D has a specific effect on erythropoiesis, or it acts via suppression of hyperparathyroidism. METHODS: We enrolled 29 patients with chronic renal failure, free from malignancies, iron deficiency or other chronic or hematological diseases. Aluminium accumulation was also excluded by DFO test. 22 were on hemodialysis and 7 on conservative management, creatinine clearance ranging 22-48 ml/min. Their mean age was 62+/-28 years and duration of renal disease was 98+/-51 months. No patient under-went rHu-Epo or Vitamin D treatment. 4 subjects were enrolled as controls. Samples of peripheral blood were drawn for the Burst Forming Unit-Erythroid (BFU-E) assay. After isolation of mononuclear cells by density gradient centrifugation with Fycoll-Hypaque, a 15-day incubation was set up with four different conditions: a) adding standard dose, 3 U/ml, of r-HuEpo (Dompè Biotec), standard colture; b) combined doses of r-HuEpo, 3 U/ml, and C (Abbott), 30 pg; c) standard dose, 3 U/ml, of r-HuEpo and high dose, 300 pg, of C; and lastly d) combined high doses of r-HuEpo, 30 U/ml, and C, 300 pg. RESULTS: In the b colture (combined low doses) a higher BFU-E proliferation was found vs standard (a) colture (33.2+/-15.5 vs 17.1+/-9.2, p<0.02); interestingly, either in the c and d studies BFU-E showed an even higher proliferation (52.3+/-24 and 86.3+/-37.8 respectively, p<0.01 vs a). No difference was found when evaluating separately preterminal and hemodialysis patients. In control subjects only colture d showed an increased BFU-E proliferation. CONCLUSIONS: C has a direct effect on erythroid precursors proliferation in vitro, acting in a sinergystic manner with rHuEpo. C may be useful as adjuvant therapy for renal anemia.
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Calcitriol/farmacología , Agonistas de los Canales de Calcio/farmacología , Células Precursoras Eritroides/citología , Células Precursoras Eritroides/efectos de los fármacos , Eritropoyetina/farmacología , Fallo Renal Crónico/sangre , División Celular , Células Cultivadas , Enfermedad Crónica , Sinergismo Farmacológico , Humanos , Fallo Renal Crónico/complicaciones , Persona de Mediana Edad , Proteínas Recombinantes , Uremia/sangre , Uremia/etiologíaRESUMEN
BACKGROUND: To evaluate the efficacy and safety of intracervical prostaglandin E2 gel applications (PgE2) for cervical ripening and induction of labor in relation to parity and admission cervical score. MATERIALS AND METHODS: One hundred and thirty-nine hospitalized patients with an unfavorable cervix (Bishop score < or = 4) received a dose of commercially available endocervical dinoprostone gel 0.5 mg. On the basis of cervical scores, the gel was reapplied at a 12-hour interval for a maximum of two doses. If cervical ripening was successful (Bishop score > 4) but labor did not start within 12 hours from the last dose of gel, labor was induced with oxytocin infusion or with 1 or 2 doses of intravaginal dinoprostone. RESULTS: Intracervical gel was effective for preparing an unfavorable cervix in 87.1% of patients. In 53.1% of nulliparous with admission Bishop < or = 2 the interval between the first application of gel and delivery was higher than 24 hours whereas in all patients with parity > or = 1 and initial Bishop score between 3 and 4 delivery was achieved within 24 hours. The cesarean delivery rates in the two groups were 23.9% and 43% respectively. CONCLUSIONS: The interval from the first application of gel to delivery is strongly influenced by parity and initial cervical score. Vaginal delivery can be expected in four fifths of patients with an unfavorable cervix who undergo pre-induction cervical ripening with prostaglandin E2 gel.
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Cuello del Útero/efectos de los fármacos , Dinoprostona/administración & dosificación , Trabajo de Parto Inducido , Adolescente , Adulto , Femenino , Geles , Humanos , Paridad , EmbarazoRESUMEN
PURPOSE: Anemia in end-stage renal disease (ESRD) patients shows a lower proliferation of erythroid progenitor cells such as burst forming unit-erythroid (BFU-E) than in normal subjects. As on-line hemodiafiltration with endogenous reinfusion(HFR) is thought to have a better biocompatibility and a wide range of uremic toxin removal, we compared the effect of serum obtained pre- and post-standard hemodialysis (HD) and HFR dialysis performed in four ESRD patients with proliferation in normal subject) (controls) bone marrow BFU-E. METHODS: Mononuclear fraction was obtained by Ficoll-Hypaque density centrifugation and studies were performed in three different conditions: standard culture, adding serum from controls, adding serum from ESRD patients pre- and post HD and HFR dialysis. BFU-E were counted after 14 days with an inverted microscope and expressed as average scores from two dishes. Standardization between experiments was checked with a control culture for each experimental culture. RESULTS: The BFU-E proliferation rate was clearly reduced by adding serum from ESRD patients either pre-HD or pre-HFR. However, while this inhibition was exacerbated by post-HD serum, it showed a significant reduction with post-HFR serum. CONCLUSIONS: This effect could be due to the removal of uremic toxins or to a lower dialysis-induced cytokine release, both mechanisms involved in erythropoiesis inhibition in ESRD.
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Fenómenos Fisiológicos Sanguíneos , Células Precursoras Eritroides/fisiología , Hemodiafiltración/métodos , Soluciones para Hemodiálisis/administración & dosificación , Fallo Renal Crónico/terapia , Células Cultivadas , Humanos , Fallo Renal Crónico/complicaciones , Persona de Mediana Edad , Uremia/etiología , Uremia/terapiaRESUMEN
BACKGROUND: Calcitriol (C) improves anemia in chronic renal failure. This improvement may be related to the suppression of iPTH release, but also to a direct effect on erythropoiesis. MATERIALS AND METHODS: In order to verify this hypothesis, 33 patients with chronic renal failure were enrolled: 24 were undergoing hemodialysis, 9 managed conservatively. All patients were free from other chronic or hematological disease, had a negative DFO test and aluminum levels below 20 mcg/l. iPTH range was 250-480 pg/l. None had yet been treated with C. In vitro study- Samples were drawn for a basal erythroid precursors (Burst Forming Unit-Erythroid BFU-E) study. After mononuclear cells were isolated by centrifugation with Ficoll-Hypaque, they were incubated for 15 days with rHuEPO 3U/ml (A), rHuEPO 3U/l + C 30 pg (B), rHuEPO 3U/ml + C 300 pg (C), rHuEPO 30 U/ml + C 300 pg (D) was performed. Ex vivo study- After the basal evaluation, 10 pts on dialysis were treated with C (Calcijex-Abbott) 1 g three times a week. BFU-E studies were performed after 1,2 and 4 months. RESULTS: In vitro, culture B showed an increased BFU-E proliferation vs A (41+/- 23 vs 27+/-15, p less than 0.02); in C and D cultures proliferation was 61+/-31 and 78+/- 42 respectively, p less than 0.01 vs A. There was no difference among pts with renal failure and pts treated conservatively. During the in vivo study all cultures showed a progressive proliferation increase, without a plateau level (basal, after 1, 2, 4 months respectively): in A: 17+/-8, 22+/-13, 30.9+/-14.9, 41.4+/-20; in B: 27.3+/-15, 35.6+/-20, 45.5+/-21, 57+/-26; in C: 48.2+/-20.6, 63.7+/-32, 75.7+/-37, 83+/-40; in D: 72+/-24, 91+/-42, 106+/-42, 110+/-42.3 (always p less than 0.001). The hematocrit and hemoglobin increase was constant but not significant. The iPTH decrease was not related to BFU-E proliferation. CONCLUSIONS: In chronic uremia C has a direct effect on erythroid precursor proliferation, both in vitro and ex vivo, with a sinergystic effect with rHuEPO. This effect is not related to iPTH suppression. C may be a useful adjuvant therapy for rHuEPO treatment.
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Calcitriol/farmacología , Eritropoyesis/efectos de los fármacos , Eritropoyetina/farmacología , Fallo Renal Crónico/sangre , Adulto , Anciano , Anemia/tratamiento farmacológico , Anemia/etiología , División Celular/efectos de los fármacos , Células Cultivadas/efectos de los fármacos , Sinergismo Farmacológico , Células Precursoras Eritroides/efectos de los fármacos , Femenino , Humanos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hiperparatiroidismo Secundario/etiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Proteínas Recombinantes , Diálisis RenalRESUMEN
The charge distribution of the heaviest fragment detected in the decay of quasiprojectiles produced in intermediate energy heavy-ion collisions has been observed to be bimodal. This feature is expected as a generic signal of phase transition in nonextensive systems. In this Letter, we present new analyses of experimental data from Au on Au collisions at 60, 80, and 100 MeV/nucleon showing that bimodality is largely independent of the data selection procedure and of entrance channel effects. An estimate of the latent heat of the transition is extracted.
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Isotopic effects in the fragmentation of excited target residues following collisions of 12C on (112,124)Sn at incident energies of 300 and 600 MeV per nucleon were studied with the INDRA 4pi detector. The measured yield ratios for light particles and fragments with atomic number Z < or = 5 obey the exponential law of isotopic scaling. The deduced scaling parameters decrease strongly with increasing centrality to values smaller than 50% of those obtained for the peripheral event groups. Symmetry-term coefficients, deduced from these data within the statistical description of isotopic scaling, are near gamma = 25 MeV for peripheral and gamma < 15 MeV for central collisions.
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BACKGROUND: Patients on chronic hemodialysis are at high risk of HCV infection due to nosocomial transmission. The strict adhesion to universal precautions is the first step in prevention, but other simple tools such as systematic monitor disinfection and the use of separate machines for anti-HCV-positive patients need to be evaluated. METHODS: A 5-year prospective study was carried out in 4 dialysis centers enrolling 135 patients. General precautions were adopted, but anti-HCV-positive patients were not isolated. In period A, lasting 24 months, monitor disinfection was performed after each dialysis session with sodium hypochlorite; peracetic acid was also used 3 times a week. In period B, lasting 36 months, 3 dialysis units (77 patients) prolonged the same preventive protocol of period A, while another unit (58 patients) also adopted the use of separate machines for anti-HCV-positive subjects. A third-generation ELISA anti-HCV test was performed every 2 months throughout the study. RESULTS: Anti-HCV antibodies were initially detected in 43 patients (31.8%), prevalence rate ranging from 25 to 39.4%. One seroconversion occurred in period A, with an overall seroconversion rate of 0.54%/year. Also in period B one seroconversion occurred (unit 2), seroconversion rate of 0.36%/year. Therefore the mean seroconversion rate throughout the 5 years was 0.43%/year. CONCLUSION: Systematic monitor disinfection may be a simple and quite effective tool to avoid nosocomial transmission of HCV infection in the hemodialysis setting. In our opinion its use is mandatory. The use of separate machines for anti-HCV-positive patients seems unnecessary.
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Desinfección/métodos , Contaminación de Equipos/prevención & control , Hepatitis C/transmisión , Diálisis Renal/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Desinfección/normas , Contaminación de Equipos/estadística & datos numéricos , Estudios de Seguimiento , Hepacivirus/genética , Hepatitis C/etiología , Hepatitis C/prevención & control , Anticuerpos contra la Hepatitis C/sangre , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Viral/sangre , ARN Viral/clasificaciónRESUMEN
Of 54 patients, we reviewed 26 with 28 operations for hallux valgus according to the Viladot-Regnauld technique. Follow-up was 18.7 (12-26) years. In 26 operations, the score according to Kitaoka and modified by Calder was excellent or good, and in two, fair. There were no complications. Average valgus angle correction was 15 degrees (8 degrees-29 degrees) and average intermetatarsal angle correction was 7 degrees (4 degrees-12 degrees). Sesamoids were medialised, on average, by at least 25% compared to the pre-operative situation. The results confirm the validity of this surgical procedure.
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Hallux Valgus/diagnóstico por imagen , Hallux Valgus/cirugía , Osteotomía/métodos , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Deformidades Adquiridas del Pie/diagnóstico por imagen , Deformidades Adquiridas del Pie/cirugía , Humanos , Masculino , Persona de Mediana Edad , Osteotomía/rehabilitación , Radiografía , Rango del Movimiento Articular/fisiología , Recuperación de la Función , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The aim of the present paper was to evaluate the effect of the 1,4 bis [3-(3,4,5-trimethoxybenzoyl-oxy) propyl] perhydro-1,4 diazepina (dilazep) on reduction of circulating platelet aggregates in 18 patients with type 2 diabetes, 13 female and 5 male, aged 25-65 years. Dilazep was orally given at 100 mg X 3/day for 8 weeks. The platelet activity has valued before and after the treatment trough the evaluation of circulating platelet aggregates with the method of Wu and Hoak. The results confirmed that the dilazep decreased statistically significant after 8 weeks the circulating aggregates.
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Azepinas/farmacología , Diabetes Mellitus Tipo 2/sangre , Dilazep/farmacología , Agregación Plaquetaria/efectos de los fármacos , Administración Oral , Adulto , Anciano , Dilazep/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We have investigated the effect of dilazep on the prostaglandin synthesis determined as indicator malondialdehyde (MDA) formation. Twenty patients with type 2 diabetes, aged 25-65 years were orally given dilazep at 100 mg X 3/day for 56 daily. The platelet activity has valued before and after the treatment with the production of the MDA. We conclude that the dilazep inhibited statistically significant biosynthesis of prostaglandin endoperoxides from arachidonic acid.
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Azepinas/farmacología , Plaquetas/metabolismo , Diabetes Mellitus Tipo 2/sangre , Dilazep/farmacología , Malonatos/sangre , Malondialdehído/sangre , Adulto , Anciano , Plaquetas/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Endoperóxidos de Prostaglandina/sangreRESUMEN
BACKGROUND: In chronic renal failure, desferrioxamine (DFO) may improve erythropoiesis independent from its aluminium (Al) chelating effect. The mechanism of this action is still unknown. METHODS: To verify whether DFO influences proliferation of erythropoietic precursors, we studied 10 patients on chronic haemodialysis, free from malignancies or other haematological diseases, iron deficiency, bone marrow fibrosis, and Al toxicity. Al accumulation was excluded by the DFO test. Peripheral blood samples were drawn for basal burst-forming unit erythroid (BFU E) assay. Mononuclear cells were isolated by density gradient centrifugation with Ficoll Hypaque, and incubated for 15 days with three different experimental conditions: (a) low-dose recombinant human erythropoietin (rHuEpo) (3 U/ml); (b) high dose rHuEpo, (30 U/ml); (c) both DFO (167 microg/ml) and rHuEpo (3 U/ml). We determined TIBC, transferrin, ferritin, reticulocytes, hypochromic erythrocytes, soluble transferrin receptor (sTR), haemoglobin (Hb), and haematocrit (Hct) at baseline and then every 14 days. Patients received 5 mg/kg DFO infused during the last hour of each dialysis session for 6 weeks; six patients remained in the study for an additional 6 more weeks. BFU E assays were set up after 6 and 12 weeks of DFO therapy. RESULTS: At baseline DFO had small effect on BFU E proliferation (33.9+/-25 vs 30.4+/-25.9) and high-dose rHuEpo had a significant effect (45.15+/-27 vs 30.4+/-25.9, P<0.01). After 6 weeks of DFO therapy a significant increase in BFU E proliferation was observed in all culture conditions (78.25+/-32 vs 30.45+/-25.9 standard culture, P<0.01; 110.9+/-30 vs 45.15+/-27 high dose rHuEpo, P<0.01; 98.75+/-32 vs 45.15+/-27 DFO culture, P<0.01). Moreover, the increase in BFU E proliferation was significant greater with DFO culture than standard culture (P<0.01). The same trend was found at the third BFU E assay, performed in only six patients, when all culture conditions showed a further increase of erythroid precursor proliferation. However, the DFO culture was not significantly greater than the standard culture, while the high-dose rHuEpo was significantly greater than the DFO culture. Patients in group I (n=10), had a significant increase in reticulocytes (1.5+/-0.6 vs 1.72+/-0.3, P<0.01) and of hypochromic erythrocytes (HE) (5.6+/-5.1 vs 14.4+/-12.7, P<0.01), while sTR, Epo, Hb, and Hct were only minimally increased. Ferritin decreased significantly (448+/-224 vs 196+/-215, P<0.01) and TIBC and transferrin were unchanged. CONCLUSIONS: Thus DFO increases erythroid activity by BFU E proliferation and increases reticulocytes in haemodialysis patients. Such an effect may be related to increased iron utilization. DFO may be a useful tool for anaemic patients with good iron stores and without Al overload.
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Deferoxamina/uso terapéutico , Células Precursoras Eritroides/efectos de los fármacos , Células Precursoras Eritroides/patología , Diálisis Renal , Anciano , Anciano de 80 o más Años , División Celular/efectos de los fármacos , Femenino , Humanos , Interleucina-1/metabolismo , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Desferrioxamine (DFO) has been suggested to improve erythropoiesis in end-stage renal failure independently of its aluminium (Al)-chelating effect. A possible synergistic effect of DFO and recombinant human erythropoietin (r-HuEpo) could be very useful in treating anaemia of chronic renal failure. METHODS: In order to verify whether a synergistic action of DFO and r-HuEpo exists, we enrolled 11 patients undergoing chronic haemodialysis and r-HuEpo treatment. All had a negative DFO test, very low serum Al levels (< 20 microg/l), ferritin > 100 ng% and iPTH < 200 pg/l. Samples were drawn for a basal erythroid precursor (burst-forming unit-Erythroid, BFU-E) evaluation. After isolation by Ficoll Hypaque, a 14 day incubation was carried out with: (i) r-HuEpo 3 U/ml; (ii) r-HuEpo 30 U/ml; and (iii) r-HuEpo 30 U/ml + DFO 167 microg/ml. Patients then received 5 mg/kg DFO infused during the last hour of each dialysis session for 12 weeks. New BFU-E evaluations were performed after 2, 6 and 12 weeks of treatment. BFU-E colonies were counted in duplicate with an inverted microscope after 14 days. Haemoglobin (Hb), ferritin, transferrin, reticulocytes, hypochromic erythrocytes, soluble transferrin receptor and serum erythropoietin were also evaluated at the same time. RESULTS: High dose r-HuEpo achieved greater proliferation than low dose r-HuEpo cultures during all phases of the study. At baseline, r-HuEpo and DFO culture had a greater number of colony units than high dose r-HuEpo culture ( 103.7 +/- 50.2 vs 95.1 +/- 50.5, NS). This increase became significant after 2 weeks (145 +/- 59.3 vs 122.9 +/- 59.6, P < 0.02), and remained so at 6 (167.4 +/- 60.3 vs 149 +/- 55.6, P < 0.01) and 12 weeks (191 +/- 64.5 vs 155.1 +/- 56.3, P < 0.01). An increased proliferation was observed after DFO therapy in all culture studies: low dose r-HuEpo culture increased from 69.4 +/- 38.2 to 86.6 +/- 48.5, 115 +/- 39 and 123 +/- 46; high dose r-HuEpo culture increased from 95.1 +/- 50.5 to 122.9 +/- 59, 149 +/- 55.6 and 155.1 +/- 56.3 and r-HuEpo plus DFO culture from 103.7 +/- 50.2 to 145 +/- 59.3, 167 +/- 60.3 and 191 +/- 64.5 at 2, 6 and 12 weeks, respectively (all P < 0.01 by ANOVA). Haemoglobin, reticulocytes and soluble transferrin receptor were slightly increased, while ferritin decreased. Hypochromic erytrocytes were variable. CONCLUSIONS: DFO increases erythroid precursor proliferation and has a synergistic in vivo effect with r-HuEpo in patients with chronic renal failure. Further investigations are needed to evaluate whether such an effect may have clinical application.