Clinical and molecular phenotype of Aicardi-Goutières syndrome

Aicardi-Goutières syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3′→5′ exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P = .001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified. © 2007 by The American Society of Human Genetics. All rights reserved.

The large vestibular aqueduct syndrome: A cause of neurosensory dysacusia

Background: The large vestibular aqueduct syndrome (LVAS) is characterized by the enlargement of the vestibular aqueduct associated with sensorioneural hearing loss. The level of hearing loss varies and may be fluctuant, progressive or sudden. Vestibular symptoms may be present. The diagnosis is reached by imaging methods. Aim: To report an LVAS case. Method: A female infant was submitted to a computerized tomography of the ears and to audiologic tests. Results: Enlargement of the vestibular aqueduct of more than 1.5mm and sensorioneural hearing loss in the right ear were observed. Conclusion: With an early hearing evaluation it is possible to diagnose hearing loss, even in children were this loss is unilateral. Although the literature indicates that the diagnosis of LVAS occurs at a later age, in this case time etiologic diagnosis was enabled by computerized tomography.

Tomografia computadorizada de abdome normal: Estudo retrospectivo das angulações dos hilos renais

OBJECTIVE: To obtain mean angulation values for renal hila in relation to the horizontal plane traced over the right and left spinal erector muscles, considering the center of the lumbar vertebral spine as a parameter for measuring the renal hila angles. MATERIALS AND METHODS: The authors have analyzed 250 abdominal computed tomography studies of both male and female healthy individuals (128 men with mean age 52.45 ± 17.42 years, and 122 women with mean age 54.39 ± 18.27 years), corresponding to 500 renal hila evaluated. The mean angulation of each hilum in relation to the horizontal plane was obtained taking acute angles into consideration. RESULTS: The comparative study have not found any statistically significant difference in acute angles of renal hila between male and female individuals. The statistical analysis demonstrated limits of 40.40° and 44.54° for mean right hilum angulation and 39.91° and 43.23° for mean left hilum angulation, with a confidence interval of 95% CONCLUSION: Renal hila present similar angulation independently of sex. Higher angulation values correspond to hyper-rotation or excessive rotation, and lower angulation values, to incomplete or reverse rotation. © Colégio Brasileiro de Radiologia e Diagnóstico por Imagem.

Técnicas de confección de prótesis facials

Facial prostheses are a integral part of rehabilitation of patients underwent face damages, being of pathologic, traumatic or congenital origin. Although success of treatment with facial prostheses is associated with artistic ability of professional to reproduce lost structures, we can not to obviate the good adaptability of prostheses regards association of material and techniques used to make buccomaxillofacial prostheses.

Regional odontodysplasia in early childhood: A clinical and histological study

Regional odontodysplasia (RO) is a rare disorder of dental development. The affected teeth are clinically hypoplastic and hypocalcified, presenting a ghost-like appearance radiographically. The aim of this work was to report a clinical case of a child with both primary and permanent dentition affected by RO. The conducted therapy was based on a conservative approach, which consisted of follow-up clinical evaluations of the anomalous teeth. However, the endodontic treatment of the primary incisors failed. Then, the chosen option for patient rehabilitation became extraction followed by removable of prosthesis confection. The extracted teeth were processed for histological analysis. In spite of the uncertain prognosis, but taking into account the psychological aspects of the patient, a conservative approach in an attempt to maintain those viable teeth in the oral cavity should be established.

Sudden cardiac death athletes: a systematic review

Previous events evidence that sudden cardiac death (SCD) in athletes is still a reality and it keeps challenging cardiologists. Considering the importance of SCD in athletes and the requisite for an update of this matter, we endeavored to describe SCD in athletes. The Medline (via PubMed) and SciELO databases were searched using the subject keywords sudden death, athletes and mortality. The incidence of SCD is expected at one case for each 200,000 young athletes per year. Overall it is resulted of complex dealings of factors such as arrhythmogenic substrate, regulator and triggers factors. In great part of deaths caused by heart disease in athletes younger than 35 years old investigations evidence cardiac congenital abnormalities. Athletes above 35 years old possibly die due to impairments of coronary heart disease, frequently caused by atherosclerosis. Myocardial ischemia and myocardial infarction are responsible for the most cases of SCD above this age (80%). Pre-participatory athletes' evaluation helps to recognize situations that may put the athlete's life in risk including cardiovascular diseases. In summary, cardiologic examinations of athletes' pre-competition routine is an important way to minimize the risk of SCD. © 2010 Ferreira et al; licensee BioMed Central Ltd.

Developmental Disturbance of an Unerupted permanent incisor due to trauma to its predecessor

Developmental disturbances of permanent teeth can result from trauma to primary teeth because of the proximity of the root of the primary teeth to their permanent successors. We describe the case of a 14-month-old boy who was referred to the baby clinic of the School of Dentistry, Universidad Estadual Paulista, Araçatuba, Brazil, after sustaining a severe trauma that led to intrusion of the right primary central incisor. Radiographic examination 4 years after the trauma showed a developing morphological change in the germ of the permanent successor. On eruption of the permanent central incisor, a crown malformation along with enamel hypoplasia was observed. We concludethat radiographic follow-up is indicated after trauma to monitor possible sequelae in the permanent successors even before their eruption. © 2011 Canadian Dental Association.

Birth defects in newborns and stillborns: An example of the Brazilian reality

Background: This study constitutes a clinical and genetic study of all newborn and stillborn infants with birth defects seen in a period of one year in a medical school hospital located in Brazil. The aims of this study were to estimate the incidence, causes and consequences of the defects. Methods. For all infants we carried out physical assessment, photographic records, analysis of medical records and collection of additional information with the family, besides the karyotypic analysis or molecular tests in indicated cases. Result: The incidence of birth defects was 2.8%. Among them, the etiology was identified in 73.6% (ci95%: 64.4-81.6%). Etiology involving the participation of genetic factors single or associated with environmental factors) was more frequent 94.5%, ci95%: 88.5-98.0%) than those caused exclusively by environmental factors (alcohol in and gestational diabetes mellitus). The conclusive or presumed diagnosis was possible in 85% of the cases. Among them, the isolated congenital heart disease (9.5%) and Down syndrome (9.5%) were the most common, followed by gastroschisis (8.4%), neural tube defects (7.4%) and clubfoot (5.3%). Maternal age, parental consanguinity, exposure to teratogenic agents and family susceptibility were some of the identified risk factors. The most common observed consequences were prolonged hospital stays and death. Conclusions: The current incidence of birth defects among newborns and stillbirths of in our population is similar to those obtained by other studies performed in Brazil and in other underdeveloped countries. Birth defects are one of the major causes leading to lost years of potential life. The study of birth defects in underdeveloped countries should continue. The identification of incidence, risk factors and consequences are essential for planning preventive measures and effective treatments. © 2011 Fett-Conte et al; licensee BioMed Central Ltd.

Análise das prevalências de doenças detectadas pelo programa nacional de triagem neonatal no município de Araraquara no ano de 2009

The National Neonatal Screening Program (NNSP) set up in all Brazil, aims, through planned phases of local implementation, to detect diseases such as phenylketonuria, congenital hypothyroidism, hemoglobinopathies and cystic fibrosis. The aim of this study was to assess, through a cross-sectional observational study, the prevalence of the diseases detected by the NNSP in the city of Araraquara, in records issued by the São Paulo APAE laboratory in the period between April and December 2009.The results show that Araraquara had a prevalence of phenylketonuria and congenital hypothyroidism 0.06% above the national averages of 0.01% and 0.03% respectively. With respect to hemoglobinopathies, the prevalence of sickle cell trait was 2.15% below the national average of 2.6%. The prevalence of Hb C in the city was 0.57%, similar to national values reported in the literature. Confirmed Hb Bart's had a prevalence of 0.13% in Araraquara, below the average of 0.38% for the surrounding region. The neonatal screening by heel-prick test and counseling for caregivers are important factors in reducing morbidity related to the evolution of these diseases.

Ocorrência de anormalidades morfológicas externas em caranguejos marinhos (Decapoda, Brachyura) no litoral norte do estado de são paulo

Deformities and abnormalities in crustaceans have been associated to genetic problem, which occurred during molt process, damage caused by ectobionts, predators or environmental stress caused by chemical wastes. Some crab specimens collected in the São Paulo littoral were found having body abnormalities. They belong to the following crab species: Callinectes ornatus (Ordway, 1863), Arenaeus cribrarius (Lamarck, 1818) and Leurocyclus tuberculosus (H. Milne Edwards; Lucas, 1843). Samplings were performed by trawling during July 2008, August and October 2009 at the Ubatuba region, São Paulo State, Brazil. Body abnormalities were verified in the cheliped dactyl (C. ornatus an adult male), carapace deformities (A. cribrarius an adult male) and abdominal alterations (C. ornatus an adult female; L. tuberculosus an adult male and an ovigerous female). The record and analysis of such occurrences can help in the distinction of natural or human impact caused alterations. In this way, the occurrence study of this kind of body alterations could provide tools in order to control unprotected environmental areas, as well as bring subsides to understand the unusual variations during the ontogeny of important species in the benthic community.

Retention and processing methods of nasal prosthesis

Patients with congenital malformations, traumatic or pathological mutilation and maxillofacial developmental disorders can be restored aesthetically and emotionally by the production and use of facial prostheses. The aim of this study was to review the literature about the retention and processing methods of facial prostheses, and discuss their characteristics. A literature review on Medline (PubMed) database was performed by using the keywords maxillofacial prosthesis, silicone, resin, pigment, cosmetic, prosthetic nose, based on articles published from 1956 to 2010. Several methods of retention, from adhesives to the placement of implants, and different processing methods such as laser, CAD/CAM and rapid prototyping technologies have been reported. There are advantages and disadvantages of each procedure, and none can be classified as better compared to others.

Heat shock protein production and immunity and altered fetal development in diabetic pregnant rats

We evaluated associations between the concentrations of heat shock proteins (hsp60 and hsp70) and their respective antibodies, alterations in maternal reproductive performance, and fetal malformations in pregnant rats with hyperglycemia. Mild diabetes (MD) or severe diabetes (SD) was induced in Sprague-Dawley rats prior to mating; non-treated non-diabetic rats (ND) served as controls. On day 21 of pregnancy, maternal blood was analyzed for hsp60 and hsp70 and their antibodies; and fetuses were weighed and analyzed for congenital malformations. Hsp and anti-hsp levels were correlated with blood glucose levels during gestation. There was a positive correlation between hsp60 and hsp70 levels and the total number of malformations (R∈=∈0.5908, P∈=∈0.0024; R∈=∈0.4877, P∈=∈0.0134, respectively) and the number of malformations per fetus (R∈=∈0.6103, P∈=∈0.0015; R∈=∈0.4875, P∈=∈0.0134, respectively). The anti-hsp60 IgG concentration was correlated with the number of malformations per fetus (R∈=∈0.3887, P∈=∈0.0451) and the anti-hsp70 IgG level correlated with the total number of malformations (R∈=∈0.3999, P∈=∈0.0387). Moreover, both hsp and anti-hsp antibodies showed negative correlations with fetal weight. The results suggest that there is a relationship between hsp60 and hsp70 levels and their respective antibodies and alterations in maternal reproductive performance and impaired fetal development and growth in pregnancies associated with diabetes. © 2012 Cell Stress Society International.

Report of cerebellar hypoplasia in three calves

Hereditary or acquired cerebellar hypoplasia (CH) is commonly diagnosed in Holstein, Guernsey, Shorthorn and Jersey cattle. Bovine viral diarrhea (BVD) has been associated to acquired CH due to viral infection during the second trimester of pregnancy. Stricken calf usually shows ataxia, hypermetria, opisthotonus, intentional tremor and wide-based stance when in standing position. Three newborn calves were referred to the FCAV/Unesp Veterinary Teaching Hospital because of neurological distress. The clinical presentation, similar in all cases, indicated CH. Two weeks later, clinical signs did not improve and euthanasia was performed. Macroscopic examination revealed a gelatinous serosanguineous fluid over the brain surface and within the cervical spinal canal. Histologically the cerebellum had disorganization of the internal granular layer and moderate disappearance of Purkinje cells. The observed clinical signs and nervous tissue lesions were consistent with congenital cerebellar syndrome, possibly associated to viral infection during fetal development. Despite CH has been assumed to be related to BVD, blue tongue and Akabane viruses, only the BVD etiology has been already identified in Brazil.

Evaluation of the biocompatibility of silicone gel implants - histomorphometric study

Breast implants are medical devices that are used to augment breast size or to reconstruct the breast following mastectomy or to correct a congenital abnormality. Breast implants consist of a silicone outer shell and a filler (most commonly silicone gel or saline). Approximately 5 to 10 million women worldwide have breast implants. Histomorphometric study to evaluate the biological tissue compatibility of silicone implants suitable for plastic surgery and the adverse effects and risks of this material. Thirty Wistar white rats received subcutaneous implants and the revestiment of silicone gel Silimed ®®, and randomized into six groups of five animals each, according to the type of implanted material and the time of sacrifice. Eight areas of 60.11mm2 corresponding to the obtained surgical pieces were analyzed, counting mesenchymal cells, eosinophils, and foreign body giant cells, observing an acceptable biocompatibility in all implants, for subsequent statistical analysis by Tukey test. Silicone gel showed inflammation slightly greater than for other groups, with tissue reactions varying from light to moderate, whose result was the formation of a fibrous capsule around the material, recognized by the organism as a foreign body. Despite frequent local complications and adverse outcomes, this research showed that the silicone and top layer presented an acceptable chronic inflammatory reaction, which did not significantly differ from the control group. In general, it is possible to affirm that silicone gel had acceptable levels of biocompatibility, confirmed the rare presence of foreign body giant cells, and when of the rupture, formed a fibrous capsule around the material, separating the material of the organism. © AVICENA 2013.

Enfisema lobar congênito: série de casos de 30 anos em dois hospitais universitários

Objetivo: Revisar os casos de enfisema lobar congênito (ELC) operados nos últimos 30 anos em dois hospitais universitários. Métodos: Foram revistos os prontuários médicos das crianças com ELC operadas no Hospital das Clínicas da Faculdade de Medicina de Botucatu e no Hospital da Universidade de Mogi das Cruzes entre 1979 e 2009. Dados sobre sintomas, exame físico, achados radiológicos, diagnóstico, tratamento cirúrgico e seguimento pós-operatório mediato e tardio foram analisados. Resultados: Durante o período estudado, 20 crianças com ELC foram submetidas a tratamento cirúrgico. A média de idade dos pacientes no momento da cirurgia foi 6,9 meses (variação, 9 dias a 4 anos). Todos os casos apresentaram sintomas ao nascimento ou nos primeiros meses de vida. Em todos os casos, a radiografia simples de tórax foi importante na definição do diagnóstico. Em casos de dificuldade respiratória moderada, a TC de tórax auxiliou no diagnóstico. Um paciente com desconforto respiratório grave foi diagnosticado erroneamente com pneumotórax hipertensivo e submetido a drenagem torácica. A broncoscopia só foi realizada nos pacientes com dificuldade respiratória moderada e não foram encontrados sinais de anomalias traqueobrônquicas. A abordagem cirúrgica foi realizada através de toracotomia lateral poupadora de músculo. O lobo superior esquerdo e o lobo médio foram os mais afetados, seguidos pelo lobo superior direito. A lobectomia foi realizada em 18 casos, enquanto a bilobectomia foi realizada em 2 casos (com ressecção de cisto broncogênico em 1 desses). Complicações pós-operatórias não foram observadas. O acompanhamento pós-operatório foi de pelo menos 24 meses (média, 60 meses) e não foram observadas complicações tardias nesta série. Conclusões: O ELC é uma doença pouco comum, ainda negligenciada, de etiologia incerta, mas de fácil diagnóstico radiológico e tratamento cirúrgico eficaz.