Henedina Antunes

Early signs and risk factors for the increased incidence of Epstein-Barr virus-related posttransplant lymphoproliferative diseases in pediatric liver transplant recipients treated with tacrolimus.

BACKGROUND Posttransplant lymphoproliferative disease (PTLD) is a life-threatening condition the incidence of which in pediatric solid organ transplantation may be related to the immunosuppressive load. It has been suggested that tacrolimus, a new and potent immunosuppressor, causes an increased incidence of this syndrome. METHODS The incidence, early signs, and risk factors for lymphoproliferative disease were reviewed in a cohort of 89 pediatric liver transplant recipients treated with tacrolimus. RESULTS Eighteen patients (20%) developed a PTLD-16 concomitant to a primary Epstein-Barr virus (EBV) infection and 2 with previous immunity against EBV. Three additional patients had preliminary signs of PTLD concomitant to primary EBV infection, but did not develop individualized lymphoid masses. Six patients died (6.7% of all tacrolimus-treated patients). Mean tacrolimus blood level during the 3 months preceding EBV infection reached 11.8+/-1.8 ng/ml in PTLD patients versus 9.4+/-3.4 ng/ml in non-PTLD patients (0.05<P<0.1). Previous OKT3 or antithymocyte globulin treatment was also significantly associated to PTLD. There was no association with age, rejection episodes, steroid-resistant rejection, prior cytomegalovirus infection, HLA mismatch, living donor or cadaveric organ transplantation, United Network for Organ Sharing status at the time of orthotopic liver transplant, and primary or rescue tacrolimus treatment. A significant increase of total gamma-globulin level occurred in PTLD patients, and mono/oligoclonal production was significantly associated to PTLD. CONCLUSION In EBV-infected pediatric liver transplant recipients, use of OKT3 or antithymocyte globulin and high tacrolimus blood levels are risk factors for a significant increase in the incidence of PTLD. An increase in total gamma-globulin level and appearance of mono/oligoclonal immunoglobulin production are the major preliminary signs of the syndrome.

Immunoglobulin heavy chain expression shapes the B cell receptor repertoire in human B cell development

Developing B cells must pass a series of checkpoints that are regulated by membrane-bound Ig(mu) through the Igalpha-Igbeta signal transducers. To determine how Ig(mu) expression affects B cell development and Ab selection in humans we analyzed Ig gene rearrangements in pro-B cells from two patients who are unable to produce Ig(mu) proteins. We find that Ig(mu) expression does not affect V(H), D, or J(H) segment usage and is not required for human Igkappa and Iglambda recombination or expression. However, the heavy and light chains found in pro-B cells differed from those in peripheral B cells in that they showed unusually long CDR3s. In addition, the Igkappa repertoire in Ig(mu)-deficient pro-B cells was skewed to downstream Jkappas and upstream Vkappas, consistent with persistent secondary V(D)J rearrangements. Thus, Ig(mu) expression is not required for secondary V(D)J recombination in pro-B cells. However, B cell receptor expression shapes the Ab repertoire in humans and is essential for selection against Abs with long CDR3s.

G2P[4] the most prevalent rotavirus genotype in 2007 winter season in an European non-vaccinated population

BACKGROUND Recently, a high prevalence of G2P[4] rotavirus (RV) infection was reported from Brazil, and linked with the universal RV vaccination programme that used the G1P[8] live oral RV vaccine. OBJECTIVE To determine the genotypes of RV co-circulating in a non-vaccinated population, in northern Portugal in the winter season of 2007. STUDY DESIGN Prospective multicenter study of the genotypes circulating in the northwest region of Portugal during January to March 2007. Children with acute gastroenteritis, who attended the Pediatric Emergency Services of five Hospitals, were included in the study. The parents of the children completed a clinical and epidemiological data questionnaire and stool samples were collected. Stool samples positive in a RV enzyme immunoassay (EIA) were genotyped by reverse transcriptase-polymerase chain reaction. RESULTS Stool samples were collected from 424 children. Two hundred and thirty-four (55.2%) stool samples were RV-positive. G2P[4] was the predominant RV type (68.6%), followed by G9P[8] (14.0%). CONCLUSIONS Because our population was naïve for RV vaccine, the G2P[4] predominance cannot be explained by vaccination. Rather, this high prevalence of G2P[4] may be within the normal fluctuation of RV genotypes. RV strain surveillance programmes are important for informing RV vaccination programmes.

Etiology of bronchiolitis in a hospitalized pediatric population: Prospective multicenter study

Abstract Background In 2006, bronchiolitis due to adenovirus nosocomial infections resulted in the closure of a pediatric department in northern Portugal. Objectives To determine the etiology of bronchiolitis in northern Portugal. Study design It was a prospective multicenter study on the etiology of bronchiolitis during the respiratory syncytial virus (RSV) season (November–April). Children ≤24 months of age admitted for a first wheezing episode were included. Nasopharyngeal specimens were analyzed by an indirect immunofluorescent-antibody assay (IFA) for RSV, adenovirus (HAdV), parainfluenza (PIV) 1–3 and influenza (IV) A and B and by polymerase chain reaction (PCR) or reverse transcription-PCR for the same viruses and for human metapneumovirus (hMPV), bocavirus (HBoV), rhinovirus (HRV), coronaviruses (229/E; NL63; OC43; HKU1) and enterovirus. Results During this period, 253 children were included, 249 IFA analyses and 207 PCRs were performed. IFA detected RSV in 58.1%; PCR increased it to 66.7%. IFA detected HAdV in 3.2%, PCR 10.0%. PCR detected IV A in 5; IV B in 2; PIV 1 in 6, PIV 2 in 4 and PIV 3 in 11 cases. HBoV, as single agent in 2 cases, and HRV were positive in 8 samples and hMPV in 11. With this virus panel, 19.7% remained without etiology. Conclusions The most frequent agent was RSV, followed by HAdV. PCR can be cost-effective and more accurate than IFA, which is crucial for HAdV that may be associated with significant mortality (IFA alone did not detect 2/3 of the cases).

Serum leptin levels in overweight children and adolescents.

Leptin is an adipocyte-secreted hormone which plays a key role in energy homeostasis. Our aim was to determine the relationship between serum leptin and clinical and biochemical features in overweight children and adolescents. Overweight children and adolescents followed in this Unit with serum leptin ascertained were included. Clinical, biochemical and abdominal ultrasound data were analysed. Statistical analysis was performed by t test, chi2, Pearsons correlation and linear regression. One outlier of serum leptin was excluded to perform correlation and regression. Serum leptin was determined in 357 patients. At the first visit, the mean age was 9.5 (sd 3.2) years and mean BMI z-score was 1.72 (sd 1.34) (girls 1.71 (sd 1.16); boys 1.72 (sd 1.11)). Serum leptin levels were significantly related to: sex (mean: girls 48.0 ng/ml, boys 34.4 ng/ml; P = 0.003); Tanner stage (mean: I-II 37.0 ng/ml, III-V 45.2 ng/ml; P = 0.035); systolic blood pressure (mean: normal 41.3 ng/ml, high 44.0 ng/ml; P = 0.009); BMI z-score (r 0.136; P = 0.010); C-peptide (r 0.17; P = 0.002); insulin (r 0.34; P < 0.001); homeostasis model assessment of insulin resistance (HOMA-IR) (r 0.25; P < 0.001) and aspartate aminotransferase (r - 0.12; P = 0.023). In the multivariate analysis (with leptin as the dependent variable and sex, Tanner stage, BMI z-score, systolic blood pressure, aspartate aminotransferase, C-peptide, insulin and HOMA-IR as independent variables), sex and BMI were determinant factors. The present study in overweight children and adolescents showed that being female and greater BMI were significantly and independently associated with increased serum leptin. In this large cohort other associations with leptin described in the literature can be discharged.

A new case of autosomal recessive agammaglobulinaemia with impaired pre-B cell differentiation due to a large deletion of the IGH locus

Males with X-linked agammaglobulinaemia (XLA) due to mutations in the Bruton tyrosine kinase gene constitute the major group of congenital hypogammaglobulinaemia with absence of peripheral B cells. In these cases, blockages between the pro-B and pre-B cell stage in the bone marrow are found. The remaining male and female cases clinically similar to XLA represent a genotypically heterogeneous group of diseases. In these patients, various autosomal recessive disorders have been identified such as mutations affecting IGHM, CD79A, IGLL1 genes involved in the composition of the pre-B cell receptor (pre-BCR) or the BLNK gene implicated in pre-BCR signal transduction. In this paper, we report on a young female patient characterised by a severe non-XLA agammaglobulinaemia that represents a new case of Igµ defect. We show that the B cell blockage at the pro-B to pre-B cell transition is due to a large homologous deletion in the IGH locus encompassing the IGHM gene leading to the inability to form a functional pre-BCR. The deletion extends from the beginning of the diversity (D) region to the IGHG2 gene, with all JH segments and IGHM, IGHD, IGHG3 and IGHG1 genes missing. Conclusion: alteration in Igµ expression seems to be relatively frequent and could account for most of the reported cases of autosomal recessive agammaglobulinaemia.

Chediak-Higashi syndrome: pathognomonic feature

A 2 -year-old girl presented to us with recurrent infections, hepato splenomegaly, and photophobia. On examination she had blond hair with a metallic sheen. The blood smear showed giant lysosomes in the white blood cells (fi gure) and we diagnosed Chediak-Higashi syndrome, a rare autosomal recessive disease (gene CHS1/LYST at 1q42.1-2). There have been around 200 cases reported, and giant cytoplasmic granules are pathognomonic. Death often occurs before the age of 7 years because of the so-called accelerated phase, with hepatosplenomegaly, lymphadenopathy, and pancyto penia or severe recurrent bacterial infections. Published Online March 29, 2013 http://dx.doi.org/10.1016/ S0140-6736(13)60020-3

Development of new spacer device geometry: a CFD study (Part I)

Asthma is a widespread disease, affecting more than 300 million individuals. The treatment in children is based upon an administration of a pressurised metered-dose inhaler added with a spacer. The efficiency of drug delivery to the patient is strongly affected by the transient airflow pattern inside the spacer device. This paper presents a computational fluid dynamics (CFD) analysis of airflow inside a commercially available spacer device with wide application. This study, carried out in Fluent™, was the basis of an optimisation procedure developed to improve the geometry of the spacer and develop a more efficient product. The results show that an appropriate control of the boundary layer development, by changing the spacer shape, reduces the length of the recirculation zones and improves the flow. It can be concluded that CFD is a powerful technique that can be successfully applied to optimise the geometry of such medical devices.

Acute pancreatitis in children: a tertiary hospital report.

Abstract Introduction. The incidence of acute pancreatitis (AP) in children has increased significantly in the past two decades. Objective. All cases of AP, acute recurrent pancreatitis (ARP), and chronic pancreatitis examined between May 2002 and May 2012 at Hospital de Braga, Portugal, were reviewed. Material and methods. Patients were identified by searching the hospitals electronic discharge records for the International Classification of Disease, Ninth Revision (ICD-9) code 577.0 (acute pancreatitis). ARP was considered as two or more episodes of AP per year or more than three episodes over a lifetime with intervening return to baseline. The following data were analyzed: demographic information, clinical, laboratory and imaging test results, etiology of pancreatitis, medical and surgical management, length of hospitalization, and outcome. The clinical and laboratory factors used in the pediatric acute pancreatitis severity score system and computed tomography severity index (CTSI) score were compared between patients with mild and severe disease. Results. A total of 37 patients, 31 episodes of AP and 6 patients with ARP, were documented. The most prevalent etiologies were biliary stones/sludge (24.3%) and trauma (16.2%). Admission elevated white blood cell count (p = 0.011), 48-h trough calcium (p = 0.007), and 48-h rise in blood urea nitrogen (p = 0.025) correlated significantly with disease severity. CTSI on admission had a score below 4 in three patients with severe disease. Conclusion. This Portuguese pediatric pancreatitis report highlights the multiple and complex etiology of this disease. Better pediatric scoring systems and management algorithms are needed.

Portuguese children's exposure to second-hand tobacco smoke in the family car

OBJECTIVES To assess the prevalence of childrens exposure to second-hand smoke in the family car; to compare exposure among children with smoking and non-smoking parents. METHODS In 2011, a self-administered questionnaire was applied to a 4th grade Portuguese children national sample (N=3187, mean age 9.5 ± 0.7, 51.1% boys). Prevalence rates and chi-square tests were computed. RESULTS Of the participants, 52.0% reported having, at least, one smoking parent. Overall exposure in the car was 28.9% (95% CI 27.3-30.5). Childrens exposure among those reporting smoking parents was 46.9% (95% CI 44.4-49.4); and 8.6% (95% CI 7.1-10.1) among those reporting non-smoking parents (p<.001). Therefore, children with smoking parents were 5.44 times more likely to be exposed. CONCLUSIONS Childrens exposure to second-hand smoke in the family car is frequent, especially if one or both parents smoke. This highlights the need for effective tobacco control measures to prevent this severe health hazard.