RESUMEN
Raising the temperature of a material enhances the thermal motion of particles. Such an increase in thermal energy commonly leads to the melting of a solid into a fluid and eventually vaporises the liquid into a gaseous phase of matter. Here, we study the finite-temperature physics of dipolar quantum fluids and find surprising deviations from this general phenomenology. In particular, we describe how heating a dipolar superfluid from near-zero temperatures can induce a phase transition to a supersolid state with a broken translational symmetry. We discuss the observation of this effect in experiments on ultracold dysprosium atoms, which opens the door for exploring the unusual thermodynamics of dipolar quantum fluids.
RESUMEN
Dipolar condensates have recently been coaxed to form the long-sought supersolid phase. While one-dimensional supersolids may be prepared by triggering a roton instability, we find that such a procedure in two dimensions (2D) leads to a loss of both global phase coherence and crystalline order. Unlike in 1D, the 2D roton modes have little in common with the supersolid configuration. We develop a finite-temperature stochastic Gross-Pitaevskii theory that includes beyond-mean-field effects to explore the formation process in 2D and find that evaporative cooling directly into the supersolid phase-hence bypassing the first-order roton instability-can produce a robust supersolid in a circular trap. Importantly, the resulting supersolid is stable at the final nonzero temperature. We then experimentally produce a 2D supersolid in a near-circular trap through such an evaporative procedure. Our work provides insight into the process of supersolid formation in 2D and defines a realistic path to the formation of large two-dimensional supersolid arrays.
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ABSTRACT: The entrance of Artificial Intelligence (AI) as a new actor in the doctor-patient relationship has encouraged important legal and ethi-cal considerations among the experts. On the one hand, there is the request to establish a new and dedicated legal background involving AI and AI-related technologies, while others believe there is no need to add new laws in the attempt to define AI's role in healthcare. The aim of this paper is to analyse the possible role of AI in civil liability in healthcare practice, underlining its limits of autonomy in a field where the attribution of liability cannot be uncertain.
Asunto(s)
Inteligencia Artificial , Responsabilidad Legal , Humanos , Relaciones Médico-PacienteRESUMEN
We report on the first realization of heteronuclear dipolar quantum mixtures of highly magnetic erbium and dysprosium atoms. With a versatile experimental setup, we demonstrate binary Bose-Einstein condensation in five different Er-Dy isotope combinations, as well as one Er-Dy Bose-Fermi mixture. Finally, we present first studies of the interspecies interaction between the two species for one mixture.
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Systemic lupus erythematosus (SLE) is a common heterogeneous autoimmune disease that is caused by the involvement both of genetic and environmental factors. There is evidence that autophagy is involved in several aspects of SLE pathogenesis. In particular, polymorphisms in the ATG5 gene have been observed to be associated with disease susceptibility. Our aim was to verify if ATG5 polymorphisms are involved in the susceptibility to disease and its clinical phenotypes in an Italian cohort of SLE patients. This study involved 315 SLE patients and 265 healthy controls. Three polymorphisms in the ATG5 gene (rs573775, rs6568431 and rs2245214) were investigated by allelic discrimination assay. A case-control association study, a genotype/phenotype correlation analysis and a haplotype study were performed. Moreover, an expression study was conducted in peripheral blood mononuclear cells from 15 SLE patients to verify a possible effect of the three SNPs on the expression of ATG5. Among the three investigated SNPs, only the rs573775 SNP was significantly associated with disease susceptibility with the variant allele conferring a higher risk of developing SLE (OR = 1.50, p = 0.018 and OR = 1.48, p = 0.007 at the genotypic and allelic level, respectively). The variant allele of rs6568431 SNP was more present in patients with anemia (OR = 1.86, p = 0.009) and renal involvement (OR = 1.63, p = 0.06), while the variant allele of rs2245214 SNP was significantly associated with a higher risk of producing anti-DNA autoantibodies (OR = 1.66, p = 0.04). Carriers of the rs6568431 variant allele showed higher messenger RNA levels compared to the carriers of the wild-type allele, suggesting also a potential variant allele dose-dependent effect on gene expression. In conclusion, our study confirms a role for ATG5 polymorphisms both in disease susceptibility and in the modulation of clinical phenotypes in an Italian SLE cohort. These results further suggest that genetic variations in autophagy genes could play a role in autoimmune diseases susceptibility and are worth further investigation.
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Proteína 5 Relacionada con la Autofagia/genética , Lupus Eritematoso Sistémico/genética , Adulto , Proteína 5 Relacionada con la Autofagia/metabolismo , Susceptibilidad a Enfermedades , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple , Estudios RetrospectivosRESUMEN
Recently, a study has shown that a polymorphism in the region of MIR1279 modulates the expression of the TRAF3IP2 gene. Since polymorphisms in the TRAF3IP2 gene have been described in association with systemic lupus erithematosus (SLE) susceptibility and with the development of pericarditis, our aim is to verify if the MIR1279 gene variability could also be involved. The rs1463335 SNP, located upstream MIR1279 gene, was analyzed by allelic discrimination assay in 315 Italian SLE patients and 201 healthy controls. Moreover, the MIR1279 gene was full sequenced in 50 patients. A case/control association study and a genotype/phenotype correlation analysis were performed. We also constructed a pericarditis genetic risk profile for patients with SLE. The full sequencing of the MIR1279 gene in patients with SLE did not reveal any novel or known variation. The variant allele of the rs1463335 SNP was significantly associated with susceptibility to pericarditis ( P = 0.017 and OR = 1.67). A risk profile model for pericarditis considering the risk alleles of MIR1279 and three other genes (STAT4, PTPN2 and TRAF3IP2) showed that patients with 4 or 5 risk alleles have a higher risk of developing pericarditis ( OR = 4.09 with P = 0.001 and OR = 6.04 with P = 0.04 respectively). In conclusion, we describe for the first time the contribution of a MIR1279 SNP in pericarditis development in patients with SLE and a genetic risk profile model that could be useful to identify patients more susceptible to developing pericarditis in SLE. This approach could help to improve the prediction and the management of this complication.
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Lupus Eritematoso Sistémico/complicaciones , MicroARNs/genética , Pericarditis/etiología , Proteínas Adaptadoras Transductoras de Señales , Adulto , Alelos , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Italia , Lupus Eritematoso Sistémico/genética , Masculino , Persona de Mediana Edad , Pericarditis/genética , Polimorfismo de Nucleótido Simple , Proteína Tirosina Fosfatasa no Receptora Tipo 2/genética , Factor de Transcripción STAT4/genética , Péptidos y Proteínas Asociados a Receptores de Factores de Necrosis Tumoral/genéticaRESUMEN
Rheumatoid arthritis (RA) is a systemic autoimmune disease resulting in chronic inflammation of the synovium and consequent cartilage and bone erosion. RA is associated strongly with the presence of rheumatoid factor (RF), and consists of clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and -negative patients. This study was designed to evaluate whether relevant single nucleotide polymorphisms (SNPs) associated with RA and other autoimmune disorders are related to RF, ACPA and clinical phenotype in a cohort of biologic drugs naive Italian RA patients; 192 RA patients and 278 age-matched healthy controls were included. Clinical and laboratory data were registered. We analysed a total of 12 single nucleotide polymorphisms (SNPs) in signal transducer and activator of transcription-4 (STAT-4), interleukin (IL)-10, psoriasis susceptibility 1 candidate 1 (PSORS1C1), protein tyrosine phosphatase, non-receptor type 2 (PTPN2), endoplasmic reticulum aminopeptidase 1 (ERAP1), tumour necrosis factor receptor-associated 3 interacting protein 2 (TRAF3IP2) and microRNA 146a (MIR146A) genes by allelic discrimination assays. Case-control association studies and genotype/phenotype correlation analyses were performed. A higher risk to develop RA was observed for rs7574865 in the STAT-4 gene, while the rs1800872 in the IL-10 gene showed a protective effect. The presence of RF was associated significantly with rs1800872 variant in IL-10, while rs2910164 in MIR146A was protective. ACPA were associated significantly with rs7574865 in STAT-4. The SNP rs2233945 in the PSORS1C1 gene was protective regarding the presence of bone erosions, while rs2542151 in PTPN2 gene was associated with joint damage. Our results confirm that polymorphisms in STAT-4 and IL-10 genes confer susceptibility to RA. For the first time, we described that SNPs in PSORS1C1, PTPN2 and MIR146A genes were associated differently with a severe disease phenotype in terms of autoantibody status and radiographic damage in an Italian RA population.
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Artritis Reumatoide/diagnóstico , Artritis Reumatoide/genética , Interleucina-10/genética , MicroARNs/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 2/genética , Proteínas/genética , Factor de Transcripción STAT4/genética , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Italia , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Fenotipo , Polimorfismo de Nucleótido Simple , Pronóstico , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
AIMS: Nuclear factor-kappaB (NF-kappaB) is an ubiquitously expressed transcription factor that modulates inducible gene transcription crucial for the regulation of immunity, inflammatory processes, and cell survival. In the mammalian nervous system, constitutive NF-kappaB activation is considered to promote neuronal cell survival by preventing apoptosis. Increasing evidence suggests a critical role for NF-kappaB activation in acute and chronic neurodegenerative diseases. Recently, a striking enrichment of phosphorylated I kappaB alpha (pI kappaB alpha) and activated I KappaB Kinase (IKK), two key components of the NF-kappaB activation pathway, was demonstrated in the axon initial segment (AIS) of neurons. As the AIS shares fundamental features with nodes of Ranvier (NR), we examined whether pI kappaB alpha and activated IKK are also enriched in NR. METHODS: Double-immunofluorescence labelling was performed with vibratome sections of the rodent central and peripheral nervous system. Sections were analysed using confocal laser scanning microscopy and preembedding electron microscopy. RESULTS: Here we report a remarkable accumulation of pI kappaB alpha and activated IKK in NR in the central and peripheral nervous system. Immunolabelling for both proteins extended from NR into the adjacent paranode. pI kappaB alpha predominantly accumulated within the cytoplasm and was associated with fasciculated microtubules. This association was confirmed by electron microscopy. By comparison, activated IKK preferentially clustered beneath the cytoplasmic membrane. CONCLUSION: In conclusion, the coincident accumulation of pI kappaB alpha and activated IKK in AIS and NR suggests that these specific axonal compartments contribute to neuronal NF-kappaB activation.
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Quinasa I-kappa B/metabolismo , Nódulos de Ranvier/enzimología , Nódulos de Ranvier/ultraestructura , Animales , Axones/enzimología , Axones/ultraestructura , Encéfalo/metabolismo , Encéfalo/ultraestructura , Activación Enzimática , Técnica del Anticuerpo Fluorescente , Ganglios Espinales/metabolismo , Ganglios Espinales/ultraestructura , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Microscopía Electrónica de Transmisión , Fosforilación , Ratas , Ratas Sprague-DawleyRESUMEN
Coxsackieviruses are human enteroviruses, which have been associated with myocarditis/pericarditis and sudden death. In one investigation (Spanakis N, Manolis EN, Tsakris A, Tsiodras S, Panagiotopoulos T, Saroglou G, and Legakis NJ: J Clin Pathol 2005;58:357-360), a cluster of cases of fatal myocarditis in Greece was linked to coxsackievirus B3. The information from this investigation prompted us to study serologically the prevalence of coxsackieviruses B throughout Greece. Sera were obtained from 506 healthy blood donors from various transfusion centers, covering the entire country. All sera were tested for the presence of IgG and IgM antibodies, using ELISAs with various antigenic specificities: (1) heat-denatured coxsackievirus type B1 and B5 virions, (2) a synthetic peptide from the N terminus of the VP1 protein of coxsackievirus B3, and (3) a synthetic peptide from the N terminus of the VP1 protein of coxsackievirus B4. Sera positive for IgG antibodies against coxsackieviruses B1/B5, B3, and B4 were detected in 6.7 to 21.6% of the individuals tested in the various regions of Greece. Statistical analysis revealed that the highest prevalence of IgG antibodies against coxsackieviruses B1/B5 was found in blood donors from Crete (p = 0.025), whereas the highest prevalence against coxsackievirus B4 was detected in blood donors from Athens (p = 0.01). IgM antibodies against coxsackievirus B were detected at low percentage, less than 5%, with no significant viral preference for particular geographic regions. The preference of anti-coxsackievirus IgG antibodies for particular geographic regions could be potentially related to the previously reported clustering of cases of insulin-dependent diabetes mellitus and myocarditis in Athens and Crete, respectively.
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Anticuerpos Antivirales/sangre , Infecciones por Coxsackievirus/epidemiología , Enterovirus Humano B/inmunología , Adulto , Secuencia de Aminoácidos , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/etiología , Ensayo de Inmunoadsorción Enzimática , Grecia/epidemiología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Datos de Secuencia Molecular , Estudios SeroepidemiológicosRESUMEN
UNLABELLED: PURPOSE AIM: To asses the diagnostic value of hysterosalpingo-contrast sonography (HyCoSy) with Levovist(R) as alternative to conventional hysterosalpingography (HSG) in the study of infertility. MATERIAL AND METHODS: From September 1988 to March 2000 we evaluated 120 patients with a history of infertility. Thirty patients underwent both HyCoSy and HSG. HyCoSy was performed in the pre-ovulatory phase of mestrual cycle. The tecnique was the same for both examinations. After administering 15 ml contrast medium, we visualized the endometrial cavity, the flow of the contrast medium along the fallopian tubes and its passage into the peritoneum. RESULTS: In all cases Color-Power Doppler allowed visualization of the uterine cavity and of the spilling of the contrast medium into the peritoneum, yielding information on tube patency that was comparable to that obtained by conventional HSG. In 28 cases (93%) we obtained optimal visualization of the contrast medium at the level of both the endometrial cavity and the fallopian tubes. HyCoSy proved to be superior to conventional HSG in evaluating adjacent myometrial structures, adnexa and degree of follicular maturation, equal to HSG in visualizing the passage of the contrast medium into the peritoneum but inferior to HSG in imaging the fallopian tubes owing to their tortuosity. DISCUSSION AND CONCLUSIONS: The absence of ionising radiation makes HyCoSy a possible first choice examination in the evaluation of fallopian tube pathology. Conventional HSG should be kept for doubtful cases or for surgical procedures to correct mono- or bilateral obstruction.
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Medios de Contraste , Pruebas de Obstrucción de las Trompas Uterinas , Trompas Uterinas/diagnóstico por imagen , Histerosalpingografía/métodos , Polisacáridos , Adulto , Femenino , Humanos , Sensibilidad y Especificidad , UltrasonografíaRESUMEN
African trypanosomiasis, or sleeping sickness, is a tropical disease caused by trypanosome parasites transmitted by tsetse flies. The focus of this paper is on the cost-effectiveness of alternative drug treatments for patients in the late stage of the disease. Melarsoprol has been used for many decades. More recently, eflornithine has been developed. It has fewer side effects and improves the overall cure rate. It is much more expensive than melarsoprol, however. The objective of the present cost-effectiveness is to identify the costs and benefits that would be involved in switching from melarsoprol to eflornithine in the treatment of late stage sleeping sickness. Benefits are expressed in lives saved as well as in disability adjusted life years (DALYs). The analysis is applied to the case of Uganda. The implications for affordability are also considered, by taking account of how the treatment costs would be shared between the national government, donors and patients. The baseline results indicate that melarsoprol treatment is associated with an incremental cost per life and DALY saved of $209 and $8, respectively. Each additional life saved by switching from melarsoprol alone to a combination of melarsoprol and eflornithine would cost an extra $1,033 per life saved, and an extra $40.9 per DALY gained. Shifting from this second alternative to treatment of all patients with eflornithine leads to an incremental cost per life saved of $4,444 and an incremental cost of $166.8 per DALY gained.
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Costo de Enfermedad , Eflornitina/economía , Asignación de Recursos para la Atención de Salud/economía , Tripanocidas/economía , Trypanosoma brucei gambiense , Tripanosomiasis Africana/tratamiento farmacológico , Animales , Análisis Costo-Beneficio , Árboles de Decisión , Progresión de la Enfermedad , Quimioterapia Combinada , Eflornitina/uso terapéutico , Ética Médica , Apoyo Financiero , Política de Salud , Humanos , Melarsoprol/efectos adversos , Melarsoprol/economía , Melarsoprol/uso terapéutico , Años de Vida Ajustados por Calidad de Vida , Recurrencia , Tripanocidas/uso terapéutico , UgandaRESUMEN
The Authors value 407 consecutive outpatients, with rhinitis, conjunctivitis and asthma, coming from Flegrean area. In the patients with prick test positivity for pollen or inhalants the results were compared with clinical symptomatology. The data obtained, confirm the importance of inhalants persistent in asthma, and the rilevance of seasonal pollens in rhinoconjunctivitis and episodic asthma. In this homogeneous population, never the olea positivity was demonstrated as a single, whereas ambrosia (ragweed) was founded.
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Hipersensibilidad Respiratoria/epidemiología , Adolescente , Adulto , Alérgenos/efectos adversos , Niño , Preescolar , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Hipersensibilidad Respiratoria/etiologíaRESUMEN
This report presents data on visual evoked potentials (VEPs) and brainstem auditory evoked potentials (BAEPs), as well as neurologic, ophthalmologic and otologic assessments performed on 120 patients with beta-thalassemia major undergoing long-term DFO treatment. A total of 32 patients showed abnormal VEPs and 14 abnormal BAEPs; seven had both VEP and BAEP abnormalities; 12 had sensorineural hearing loss (SNHL); 18 had conductive hearing loss, while 14 showed a combination of SNHL and conductive hearing loss. After DFO administration was modified (taking in consideration the serum ferritin levels) patients with abnormal findings were retested. The values of 15 patients of 23 who underwent VEP examinations had been normalized. Eleven of 15 who repeated the BAEP test had also gained normal values. The audiogram had not returned to normal in any patient with SNHL. In a second repetition of the examinations, no change was observed. It is concluded that in a great percentage of thalassemics at least one of the above examinations shows abnormal values. These abnormalities are mostly reversible, and probably reflect a dysfunction of the visual or auditory system, due either to DFO neurotoxicity or to iron overload or both.
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Deferoxamina/efectos adversos , Electroencefalografía/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Potenciales Evocados Visuales/efectos de los fármacos , Pérdida Auditiva Sensorineural/inducido químicamente , Transmisión Sináptica/efectos de los fármacos , Talasemia/fisiopatología , Adulto , Audiometría de Tonos Puros , Umbral Auditivo/efectos de los fármacos , Umbral Auditivo/fisiología , Transfusión Sanguínea , Tronco Encefálico/efectos de los fármacos , Tronco Encefálico/fisiopatología , Deferoxamina/administración & dosificación , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Potenciales Evocados Visuales/fisiología , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/fisiopatología , Homocigoto , Humanos , Transmisión Sináptica/fisiología , Talasemia/tratamiento farmacológico , Talasemia/genética , Trastornos de la Visión/inducido químicamente , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/fisiopatología , Corteza Visual/efectos de los fármacos , Corteza Visual/fisiopatologíaRESUMEN
The activity of reticuloendothelial system (RES) was estimated in 19 patients with beta-thalassemia major, 20 +/- 4 years old, who had undergone successful splenectomy 6 +/- 5 years previously. The kinetics of 125I denatured human serum albumin in low and large doses was applied for this purpose and the parameters derived (effective RES blood flow-ERBF- and maximum phagocytic capacity-PCmax) were compared to those of nonsplenectomized thalassemics, detected in previous works, as well as to those of 13 healthy controls. In splenectomised thalassemics both parameters of RES activity were found significantly lower than those of nonsplenectomized patients (p less than 0.001). Compared to those of healthy controls, PCmax of splenectomised thalassemics was found not to be significantly different, while ERBF was significantly lower (p less than 0.001). No correlation was noted between the above parameters of RES function and the age of the patients, the age at which splenectomy was performed, the time lapsed since the operation, the amount of blood transfused to the patients after splenectomy or their serum ferritin levels. A pilot study performed in 6 out of the 19 splenectomised patients did not reveal any effect of blood transfusion on RES function parameters, by contrast to observations in nonsplenectomized thalassemics. The results of this study suggest that in splenectomised thalassemics the remaining RES reacts to the continuing hemolytic stimulus in a manner different than that of splenic RES of nonsplenectomized patients and account for, at least in part, the predisposition of the former group to infections.
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Sistema Mononuclear Fagocítico/fisiopatología , Esplenectomía , Talasemia/fisiopatología , Adolescente , Adulto , Transfusión Sanguínea , Femenino , Humanos , Masculino , Tasa de Depuración Metabólica , Fagocitosis , Proyectos Piloto , Periodo Posoperatorio , Flujo Sanguíneo Regional , Albúmina Sérica/metabolismo , Talasemia/cirugíaRESUMEN
Patients with thalassemia who receive multiple blood transfusions are at risk for the acquired immunodeficiency syndrome. Peripheral blood lymphocyte subpopulations were studied in 22 multitransfused thalassemic patients; 10 patients were without splenectomy and 12 were studied after splenectomy. Both groups were negative for anti-HIV. Four additional patients who were found positive for anti-HIV and ten healthy controls were also included in this study. Patients without splenectomy compared to controls and to patients after splenectomy showed a significant decrease of both percentage (p less than 0.001) and absolute numbers (p less than 0.001) of Leu-7+ cells without significant abnormalities of T4/T8 ratio (1.56 +/- 0.4). Patients after splenectomy compared to controls and to patients without splenectomy showed a significant increase of the absolute numbers of lymphocytes and lymphocytes subsets T11+, T3+, T4+, T8+ and SmIg+ cells. In the seropositive patients for HIV only a significant increase of the absolute number of T8+ cells was observed while the T4/T8 ratio was 1.24 +/- 0.73. The decrease in the percentage of Leu-7+ cells in patients without splenectomy correlated inversely to the total amount of blood transfused. In conclusion patients with thalassemia had normal T4/T8 ratio and did not show the abnormal immunologic profile that has been reported in haemophiliacs.
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Anticuerpos Antivirales/análisis , Talasemia/inmunología , Adolescente , Adulto , Antígenos de Diferenciación de Linfocitos T , Antígenos de Superficie/inmunología , Transfusión Sanguínea , Niño , Femenino , Grecia , Anticuerpos Anti-VIH , Hemofilia A/inmunología , Humanos , Inmunoglobulina G/análisis , Células Asesinas Naturales/inmunología , Masculino , Monocitos/inmunología , Linfocitos T/clasificaciónRESUMEN
The concentration of plasma Fn was determined in non-splenectomized and splenectomized patients with homozygous beta-thalassemia, before and 7-10 days after blood transfusion. The mean Fn concentration of non-splenectomized patients before transfusion did not differ from that of matched normal controls but appeared significantly decreased following blood transfusion. On the other hand, in splenectomized thalassemics, Fn levels were increased but were unrelated to transfusion. It is concluded that Fn plays some homeostatic function when RES activity of thalassemic patients is altered either as a result of splenectomy or blood transfusion.
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Transfusión Sanguínea , Fibronectinas/sangre , Bazo/fisiología , Talasemia/sangre , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , EsplenectomíaRESUMEN
The distribution of phenotypes and gene frequencies of the third component of complement (C3) were studied in 106 beta-thalassemic patients and in 112 carriers of the beta-thalassemia trait. A statistically significant association was found between the C3F gene and homozygous beta-thalassemia. It can be suggested that this association may be related with the high incidence of infections encountered in these patients.