Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings,histological profile,treatments, and outcomes

ObjectiveThis large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis.MethodsThe medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments.ResultsOf all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%).ConclusionsIn this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.     

Reduced toxicity of F-deficient Sendai virus vector in the mouse fetus

Current concerns over insertional mutagenesis by retroviral vectors mitigate investigations into alternative, potentially persistent gene therapy vector systems not dependent on genomic integration, such as Sendai virus vectors (SeVV). Prenatal gene therapy requires efficient gene delivery to several tissues, which may not be achievable by somatic gene transfer to the adult. Initially, to test the potential and tropism of the SeVV for gene delivery to fetal tissues, first-generation (replication- and propagation-competent) recombinant SeVV, expressing beta-galactosidase was introduced into late gestation immunocompetent mice via the amniotic and peritoneal cavities and the yolk sac vessels. At 2 days, this resulted in very high levels of expression particularly in the airway epithelium, mesothelium and vascular endothelium, respectively. However, as expected, substantial vector toxicity was observed. The efficiency of gene transfer and the level of gene expression were then examined using a second-generation SeVV. The second generation was developed to be still capable of cytoplasmic RNA replication and therefore high-level gene expression, but incapable of vector spread due to lack of the gene for viral F-protein. Vector was introduced into the fetal amniotic and peritoneal cavities, intravascularly, intramuscularly and intraspinally; at 2 days, expression was observed in the airway epithelia, peritoneal mesothelia, unidentified cells in the gut wall, locally at the site of muscle injection and in the dorsal root ganglia, respectively. Mortality was dramatically diminished compared with the first-generation vector.     

Clinical trial evaluating Viscoat and Visthesia ophthalmic viscosurgical devices in corneal endothelial loss after cataract extraction and intraocular lens implantation

Purpose: To assess and compare the safety and the efficacy of VisThesia? and Viscoat® in cataract surgery.

Methods: This prospective randomized clinical trial included 44 eyes of 44 patients that were assigned randomly to undergo phacoemulsification either with VisThesia? or with Viscoat®. Preoperative data included age, gender, visual acuity, IOP and mean endothelial cell density. Postoperative, best corrected visual acuity (BCVA), IOP, mean endothelial cell density and painful sensation during surgery were recorded.

Results: BCVA, evaluated with Snellen chart in decimal fraction, was statistically improved in both groups. Specifically, mean BCVA in VisThesia group was increased from 0.28?±?1.8 SD preoperatively to 0.83?±?1.4 SD postoperatively, whereas, in the Viscoat group, BCVA was increased from 0.31?±?2.1 SD preoperatively, to 0.85?±?1.2 SD after surgery (p?>?0.1). The mean postoperative IOP was lower in the VisThesia group, but the difference was not statistically significant (p?>?0.1). Preoperatively, the mean endothelial cell count was 2322.3?±?161.1 SD cells/mm² in Viscoat group and 2304.8?±?142.8 SD cells/mm² in the VisThesia group, similar between groups (p?>?0.1). At day 15 after cataract surgery the postoperative endothelial cell count was 2102.9?±?182.8 SD cells/mm² in Viscoat group and 2032.6?±?160.4 SD cells/mm² in the VisThesia group (p?>?0.1). The mean endothelial cell decrease was 212?cells/mm² (9.1%) in the Viscoat group and 272?cells/mm² (11.8%) in the VisThesia group. The difference was not statistically significant between the two groups (t-test?=?0.18, p?>?0.1). This value is within standard normal endothelial cell decrease after a cataract surgery. Painful sensation was not reported during any stage of the procedure.

Conclusions: Topical-intracameral anesthesia with VisThesia? allows cataract surgery without any painful sensation in the majority of patients. Both Viscoat® and VisThesia? have similar safety profile during intra- and post-operative period and identical endothelial protection, as endothelial cell loss is within normal limits.     

Factors influencing adenovirus-mediated airway transduction in fetal mice.

Intra-amniotic injection of adenovirus allows transduction of the fetal airways following natural fetal breathing movements. This administration method is promising for use in gene therapy for cystic fibrosis and other diseases for which the main target for exogenous gene expression is the lung. Here we have investigated factors that may affect the efficacy of gene transfer to the murine fetal lung. We examined marker compound distribution and transgene expression (from a first-generation adenoviral vector) at different stages of development. This demonstrated that fetal breathing movements at 15-16 days of gestation are of sufficient intensity to carry marker/vector into the fetal lungs. These movements can be significantly stimulated by the combination of intra-amniotic theophylline administration and postoperative exposure of the dam to elevated CO(2) levels. However, the most important factor for efficient and consistent pulmonary transgene delivery is the dose of adenoviral vector used, as both the degree of transduction and the percentage of lungs transduced increases with escalating viral dose.     

Megakaryocytes require thrombospondin-2 for normal platelet formation and function

Mice that lack the matricellular angiogenesis inhibitor, thrombospondin-2 (TSP2), display a bleeding diathesis, despite normal blood coagulation and the lack of thrombocytopenia. Although platelets do not contain detectable levels of TSP2, TSP2-null platelets are compromised in their ability to aggregate in vivo in response to denudation of the carotid artery endothelium, and in vitro following exposure to adenosine diphosphate (ADP). Megakaryocytes (MKs) show high levels of TSP2 by immunohistochemical analysis of bone marrow. However, when cultured in vitro, MKs contain little TSP2 protein or mRNA. These findings suggest that most TSP2 is acquired from the bone marrow microenvironment. Consistent with this hypothesis, MKs take up recombinant TSP2 in an integrin-dependent manner when it is supplied in the culture medium. Furthermore, uptake of TSP2 in vitro affects MK differentiation and proplatelet formation. The functional significance of this process is supported by the presence of ultrastructural abnormalities in TSP2-null bone marrow, including extensive fragmentation of the peripheral zone in MKs and failure of this zone to form close associations with vascular sinuses. We conclude that the uptake of TSP2 by MKs from the marrow milieu is required for proper MK function and the release of functionally competent platelets.     

Upper gastrointestinal fiberoptic endoscopy in pediatric patients

Upper gastrointestinal fiberendoscopy in pediatric patients is done safely and under local anesthesia in most instances. This study of 47 children confirmed the value of fiberendoscopy in establishing the etiology of upper gastrointestinal hemorrhage and the presence of esophageal varices. It also contributed significantly to the management of patients with disphagia, pyrosis, epigastric pain, and ingestion of foreign bodies. No significant morbidity was caused.     

Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling

Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds. As in humans, TEVGs implanted in a mouse host as venous interposition grafts gradually transformed into living blood vessels over a 6-month time course. Seeded hBMCs, however, were no longer detectable within a few days of implantation. Instead, scaffolds were initially repopulated by mouse monocytes and subsequently repopulated by mouse SMCs and ECs. Seeded BMCs secreted significant amounts of monocyte chemoattractant protein-1 and increased early monocyte recruitment. These findings suggest TEVGs transform into functional neovessels via an inflammatory process of vascular remodeling.     

Bone Marrow Mononuclear Cell Transplantation Improves Survival and Induces Hepatocyte Proliferation in Rats after CCl<Subscript>4</Subscript> Acute Liver Damage

Aim  

The aim of this research was to evaluate the effects of bone marrow mononuclear cell (BMC) transplantation in rats with toxic acute liver damage induced by carbon tetrachloride (CCl₄).     

Blastic natural killer (NK)-cell lymphoma: report of an unusual CD4 negative case and review of the CD4 negative neoplasms with blastic features in the literature

Blastic Natural Killer (NK)-cell lymphoma is a relatively new entity which has been recently included in the WHO classification. CD4 expression is observed in most cases of blastic NK-cell lymphomas and has been related with skin tropism. We report an unusual CD4 negative blastic NK-cell lymphoma with primary presentation in the skin, subsequent infiltration of the bone marrow and aggressive behavior. It is emphasized that extensive immunophenotyping and EBER RNA in situ hybridization are required in order to establish the diagnosis of blastic NK-cell lymphoma. We also present a review of the literature with respect to the CD4 negative NK-cell lymphomas with blastic morphological features.