Impaired gallbladder motility and delayed orocecal transit contribute to pigment gallstone and biliary sludge formation in β-thalassemia major adults

Aim: Gallbladder and gastrointestinal motility defects exist in gallstones patients and to a lesser extent in pigment gallstone patients. To investigated the role of gallbladder and gastrointestinal motility disorders in pigment gallstone formation in β-thalassemia major. Methods: Twenty-three patients with β-thalassemia major (16 females; age range 18-37 years) and 70 controls (47 females, age range 18-40 years) were studied for gallbladder and gastric emptying (functional ultrasonography), orocecal transit (OCTT, H2-breath test), autonomic dysfunction (sweat-spot, cardiorespiratory reflex tests), bowel habits, gastrointestinal symptoms and quality of life (all with questionnaires). Gallbladder content (ultrasonography) was examined before and during 8-12 mo follow-up. Results: Gallstones and/or biliary sludge were found in 13 (56%) patients. β-thalassemia major patients had increased fasting (38.0±4.8 mL vs 20.3±0.7 mL, P = 0.0001) and residual (7.9±1.3 mL vs 5.1±0.3 mL, P = 0.002) volume and slightly slower emptying (24.9±1.7 min vs 20.1±0.7 min, P = 0.04) of the gallbladder, together with longer OCTT (132.2±7.8 min vs 99.7±2.3 min, P = 0.00003) than controls. No differences in gastric emptying and bowel habits were found. Also, patients had higher dyspepsia (score: 6.7±1.2 vs 4.9±0.2, P = 0.027), greater appetite (P = 0.000004) and lower health perception (P = 0.00002) than controls. Autonomic dysfunction was diagnosed in 52% of patients (positive tests: 76.2% and 66.7% for parasympathetic and sympathetic involvement, respectively). Patients developing sludge during follow-up (38%, 2 with prior stones) had increased fasting and residual gallbladder volume. Conclusion: Adult β-thalassemia major patients have gallbladder dysmotility associated with delayed small intestinal transit and autonomic dysfunction. These abnormalities apparently contribute together with haemolytic hyperbilirubinemia to the pathogenesis of pigment gallstones/ sludge in β-thalassemia major. Copyright © 2004 by The WJG Press

Bioética e direitos fundamentais: a recusa às transfusões de sangue pelas Testemunhas de Jeová

This paper will examine the Institute of Bioethics and fundamental rights in the face of the refusal of blood transfusions by Jehovah's Witnesses. Based on investigating the motives involved in this decision and what legal support they have for their will to be recognized. It is a right provided for in the Federal Constitution that guarantees the patient's autonomy to avail himself of his existential choices, however, that is in conflict with the divergent position of the doctors who seek the judicial route to impose on the patient the use of hemotherapy against his will , provoking state intervention based on the claim that the individual's decision causes the collision of fundamental principles, such as the right to life and the right to religious freedom. For this, we studied bibliographies, laws of the current legal order, articles and jurisprudence, what remained for demonstrating the non-occurrence of a collision of fundamental rights, bearing in mind that Jehovah's Witnesses do not want to have their right to life, for religious reasons, but to guarantee it in its integral form by accepting the use of alternative methods. The existence of legitimacy in refusing blood transfusions based on fundamental principles, especially on the right to life, made possible by the recognition of blood as a risk treatment and the use of alternatives to blood transfusion.Trabalho de Conclusão de Curso (Graduação)Este trabalho analisará o instituto da Bioética e direitos fundamentais diante da recusa das transfusões de sangue pelas Testemunhas de Jeová. Tendo por base investigar os motivos que envolvem essa decisão e qual o respaldo legal possuem para que se reconheça a sua vontade. Trata-se de direito previsto na Constituição Federal que garante a autonomia do paciente de se valer de suas escolhas existenciais, porém que se choca com o divergente posicionamento dos médicos que buscam a via judicial para impor ao paciente o uso da hemoterapia contra sua vontade provocando a intervenção estatal fundamentada na alegação de que a decisão do indivíduo causa a colisão de princípios fundamentais (direito à vida versus direito à liberdade religiosa). Para isso, foram estudadas bibliografias, leis do ordenamento jurídico vigente; artigos e jurisprudências; que restaram por demonstrar a não ocorrência de colisão de direitos fundamentais, tendo em vista que as Testemunhas de Jeová não querem dispor de seu direito à vida, por fundamento religioso, e sim de garanti-lo em sua forma integral por aceitar a utilização de melhores métodos. Portanto, comprovando-se a existência de legitimidade na recusa às transfusões de sangue com base nos princípios fundamentais, principalmente no direito à vida, possibilitada pelo reconhecimento do sangue como um tratamento de risco e a utilização de alternativas a estes

Zero expiratory pressure and low oxygen concentration promote heterogeneity of regional ventilation and lung densities

BackgroundIt is not well known what is the main mechanism causing lung heterogeneity in healthy lungs under mechanical ventilation. We aimed to investigate the mechanisms causing heterogeneity of regional ventilation and parenchymal densities in healthy lungs under anesthesia and mechanical ventilation. MethodsIn a small animal model, synchrotron imaging was used to measure lung aeration and regional-specific ventilation (sV.). Heterogeneity of ventilation was calculated as the coefficient of variation in sV. (CVsV.). The coefficient of variation in lung densities (CVD) was calculated for all lung tissue, and within hyperinflated, normally and poorly aerated areas. Three conditions were studied: zero end-expiratory pressure (ZEEP) and FIO2 0.21; ZEEP and FIO2 1.0; PEEP 12 cmH(2)O and F(I)O(2)1.0 (Open Lung-PEEP = OLP). ResultsThe mean tissue density at OLP was lower than ZEEP-1.0 and ZEEP-0.21. There were larger subregions with low sV. and poor aeration at ZEEP-0.21 than at OLP: 12.9 9.0 vs. 0.6 +/- 0.4% in the non-dependent level, and 17.5 +/- 8.2 vs. 0.4 +/- 0.1% in the dependent one (P = 0.041). The CVsV. of the total imaged lung at PEEP 12 cmH(2)O was significantly lower than on ZEEP, regardless of FIO2, indicating more heterogeneity of ventilation during ZEEP (0.23 +/- 0.03 vs. 0.54 +/- 0.37, P = 0.049). CVD changed over the different mechanical ventilation settings (P = 0.011); predominantly, CVD increased during ZEEP. The spatial distribution of the CVD calculated for the poorly aerated density category changed with the mechanical ventilation settings, increasing in the dependent level during ZEEP. ConclusionZEEP together with low FIO2 promoted heterogeneity of ventilation and lung tissue densities, fostering a greater amount of airway closure and ventilation inhomogeneities in poorly aerated regions.Peer reviewe

Lymphocyte subset reconstitution after HLA-identical placental blood transplantation (PBT) or PBT plus bone marrow transplantation (BMT) in three children with β-thalassemia major

The kinetics of circulating lymphoid cells were evaluated in three children suffering from β-thalassemia major after HLA-identical sibling placental blood transplant (PBT) in one patient and placental blood plus bone marrow transplantation (BMT) in two patients. Recovery of the main lymphocyte subsets, as determined by phenotype analysis of circulating PBMCs, was complete within 2 months after transplant. NK (CD56+) cells were the first to appear in peripheral blood, followed by T (CD3+, CD2+, CD7+) and B (CD19+) cells. Of the T lymphocytes, the CD8+ were the first to reconstitute, but recovery of CD4+ cells was also rapid and within 6 months these T cells reached normal values. The expression of CD57 by NK or T cells was slightly delayed. The evaluation of RA and RO isoform expression of the CD45 molecule showed a prevalence of the CD45RA antigen with a ratio of 2-3:1. In the PBT only patient, T cells expressing the CD45RO antigen prevailed in the early post-transplant period. Severe or chronic GVHD was not observed. This experience demonstrates that reconstitution of lymphocyte subsets is successful in genetic hematological diseases after transplantation of HLA-identical placental blood or placental blood plus bone marrow from healthy or heterozygous siblings

Prenatal diagnosis of thalassaemia major resulting from Lepore/ beta-thalassaemia genotype.

Antenatal diagnosis was carried out in a pregnancy at risk for beta-thalassaemia major/intermedia, resulting from the Lepore/ beta-thalassaemia genotype, by globin chain synthesis analysis on fetal blood obtained by placentocentesis at 19 weeks' gestation. As there was no radioactive incorporation in the beta-region, the fetus was considered to be a Lepore/ beta-thalassaemia genetic compound and aborted on parental request. After abortion, cord blood analysis confirmed the absence of beta-chain radioactivity