The cellular basis of a congenital heart defect Drosophila

RESUMO: Mutações em genes envolvidos na formação do coração e anomalias em qualquer etapa deste processo causam frequentemente malformações cardíacas, que representam o tipo mais comum de defeitos em neonatais, afetando cerca de 1% dos nascimentos por ano. Assim, estima-se que 20 milhões de pessoas sejam portadoras de um defeito cardíaco congénito. O coração da Drosophila melanogaster (mosca-da-fruta), denominado vaso dorsal, é um órgão relativamente simples que actua como uma bomba muscular, contraindo automaticamente para permitir a circulação da hemolinfa através do corpo. A formação do vaso dorsal na mosca é muito semelhante ao desenvolvimento do coração em vertebrados, representando por isso, um poderoso modelo para estudar a rede de genes e os padrões regulatórios relacionados com o desenvolvimento deste órgão. Anteriormente, nós identificámos um gene em Drosophila, darhgef10, fortemente expresso no coração em desenvolvimento e cuja deleção induz anormalidades cardíacas subtis mas prevalentes. Os mutantes para darhgef10 são viáveis e férteis no ambiente controlado de laboratório. Este trabalho teve como objectivos caracterizar fenotipicamente os mutantes nulos para darhgef10, determinar a localização subcelular da proteína dArhgef10 e investigar a base celular subjacente ao defeito no alinhamento dos cardioblastos observado nos mutantes. Os nossos resultados revelaram que a deleção de darhgef10 provoca uma severa redução da viabilidade, sem no entanto comprometer o tempo de desenvolvimento e a longevidade. Por outro lado, o aumento da expressão de darhgef10 em músculos, glândulas salivares e no disco imaginal do olho afeta drasticamente a integridade destes tecidos. A expressão ectópica de darhgef10 in vitro e in vivo revelou que a proteína está localiza no citoplasma com enriquecimento junto à membrana celular, com associação à actina F. Live imaging de embriões mutantes para darhgef10 revelou que os defeitos observados no coração podem estar associados a um defeito na adesão dos músculos alary e/ou das células pericardiais ao vaso dorsal. O homólogo humano de darhgef10, ARHGEF10, também é expresso no coração e está associação a uma maior susceptibilidade para a ocorrência de acidentes vasculares cerebrais aterotrombóticos, sugerindo que o que aprendemos sobre darhgef10 em Drosophila pode ter implicações do ponto de vista clínico para a saúde humana. ----------------------------- ABSTRACT: Mutations in genes controlling heart development and abnormalities in any of its steps frequently cause cardiac malformations, the most common type of birth defects in humans, affecting nearly 1% of births per year. Hence around 20 million adults are expected to live with a congenital heart defect. The Drosophila melanogaster heart, called dorsal vessel, is a relatively simple organ that acts as a muscular pump contracting automatically to allow the circulation of hemolymph. Drosophila heart formation shares many similarities with heart development in vertebrates providing a powerful system to study gene networks and regulatory pathways involved in heart development. We have previously identified a Drosophila gene, darhgef10, which is strongly expressed in the developing heart and when deleted, leads to flies with highly prevalent yet subtle heart abnormalities, compatible with unchallenged life in the laboratory. Our aims were to phenotypically characterize homozygous null darhgef10 mutants, characterize the subcellular localization of dArhgef10 and to study the cellular basis of the misaligned cardioblasts defect. We found that about half of darhgef10 mutants die during development. However, the survivors surprisingly have a nearly normal developmental time, adult locomotor behavior and total lifespan. Detection of transgene-derived dArhgef10 protein in vitro and in vivo using custom antibodies revealed a cytosolic protein slightly enriched in the cellular membranes and associated with F-actin. Tissue-specific darhgef10 expression disrupts the normal morphology of developing muscles, salivary glands and the eye. Live imaging of darhgef10 mutant embryos revealed that heart defect could be caused by a reduced capacity of attachment of pericardial cells and/or alary muscle to dorsal vessel. The human homolog of darhgef10 is also expressed in the heart and is a susceptibility gene for atherothrombotic stroke, suggesting that what we learn about the function of this gene and its phenotypes in Drosophila could have implications to human health.

Incidence of congenital syphilis in the South Region of Brazil

Introduction The aim of this study was to establish the incidence rates of congenital syphilis in the South Region of Brazil from 2001 to 2009. Methods Temporal ecological and descriptive study based on the cases recorded by the System of Information of Notifiable Diseases. Results The incidence of congenital syphilis has been increasing in the South Region of Brazil since 2004; the highest incidence rates were in women who received prenatal care (113.5 new cases per 100,000 births, p<0.001), who were diagnosed with syphilis at pregnancy (69.8 new cases per 100,000 births, p=0.001), and whose partner did not undergo treatment for syphilis (53.1 new cases per 100,000 births, p=0.001). Conclusions The population of the present study mostly consisted of adult black women with low educational levels who attended prenatal care, who were diagnosed with syphilis during pregnancy, and whose partners were not treated for syphilis. Based on these results, actions are recommended to reduce the incidence of this disease, which is preventable by early diagnosis and appropriate treatment. The present was merely an ecological study; therefore, further investigations are necessary to elucidate the causes of these findings.

Evaluation of preventative and control measures for congenital syphilis in State of Mato Grosso

Introduction Congenital syphilis is an important health problem in Brazil. This study assessed measures aimed at the prevention and control of syphilis in the State of Mato Grosso and its capital, Cuiabá. Methods A descriptive study cross-sectional and of time trends assessing the congenital syphilis was performed in Cuiabá and Mato Grosso between 2001 and 2011. We compared maternal sociodemographic characteristics and health care utilization related to cases of congenital syphilis during the periods from 2001 to 2006 and from 2007 to 2011. We assessed the temporal trends in this disease's incidence using a simple linear regression. Results Between 2001 and 2006 in Mato Grosso, 86.8% of the mothers who had live births with congenital syphilis received prenatal care, 90.6% presented with a nontreponemal test reagent at delivery, 96.2% had no information regarding a treponemal confirmatory test at delivery, and 77.6% received inadequate treatment for syphilis; additionally, 75.8% of their partners were not treated. There was a statistically significant reduction in prenatal visits (p = 0.004) and an increase in the proportion of mothers reactive to nontreponemal tests at delivery (p = 0.031) between the two periods. No other variables were found to differ significantly between the periods. In Cuiabá, we observed a similar distribution of variables. In the state and in the capital, the increasing trend of congenital syphilis was not statistically significant. Conclusions The high incidence of congenital syphilis in Mato Grosso and the low levels of health care indicators for pregnant women with syphilis suggest the need to improve the coverage and quality of prenatal care.

The use of saliva as a practical and feasible alternative to urine in large-scale screening for congenital cytomegalovirus infection increasesinclusion and detection rates

INTRODUCTION: Although urine is considered the gold-standard material for the detection of congenital cytomegalovirus (CMV) infection, it can be difficult to obtain in newborns. The aim of this study was to compare the efficiency of detection of congenital CMV infection in saliva and urine samples. METHODS: One thousand newborns were included in the study. Congenital cytomegalovirus deoxyribonucleic acid (DNA) was detected by polymerase chain reaction (PCR). RESULTS: Saliva samples were obtained from all the newborns, whereas urine collection was successful in only 333 cases. There was no statistically significant difference between the use of saliva alone or saliva and urine collected simultaneously for the detection of CMV infection. CONCLUSIONS: Saliva samples can be used in large-scale neonatal screening for CMV infection.

Congenital and maternal syphilis in the capital of Brazil

INTRODUCTION: ​This study aimed to describe the epidemiology of congenital and maternal syphilis in the Brazilian Federal District in 2010. ​ METHODS: ​A retrospective descriptive study was conducted on the basis of the cases recorded in the System of Notifiable Disease Information. RESULTS: ​The study population comprised 133 cases of congenital syphilis; of these, 116 (52.6%) mothers received prenatal care, and 70 (60.4%) were diagnosed with syphilis during pregnancy. Only 1 mother was adequately treated, and 100 (75.2%) of the pregnant women's partners did not undergo treatment for syphilis. ​ CONCLUSIONS: Although mothers attended prenatal care, not all were diagnosed during pregnancy or received adequate treatment for syphilis, as their partners did not undergo treatment for syphilis.

Congenital hyperthyroidism: autopsy report

We report the autopsy of a stillborn fetus with congenital hyperthyroidism born to a mother with untreated Graves' disease, whose cause of death was congestive heart failure. The major findings concerned the skull, thyroid, heart, and placenta. The cranial sutures were closed, with overlapping skull bones. The thyroid was increased in volume and had intense blood congestion. Histological examination showed hyperactive follicles. The heart was enlarged and softened, with dilated cavities and hemorrhagic suffusions in the epicardium. The placenta had infarctions that involved at least 20% of its surface, and the vessels of the umbilical cord were fully exposed due to a decrease in Wharton 's jelly. Hyperthyroidism was confirmed by the maternal clinical data, the fetal findings of exophthalmia, craniosynostosis, and goiter with signs of follicular hyperactivity. Craniosynostosis is caused by the anabolic action of thyroid hormones in bone formation during the initial stages of development. The delayed initiation of treatment in the present case contributed to the severity of fetal hyperthyroidism and consequent fetal death.

Rectangular flaps technique for treatment of congenital hand syndactyly

The authors analysed a series of 22 patients undergoing surgical correction of congenital hand syndactyly by the rectangular flap technique. Using our evaluation method, we found that good functional and aesthetic results were obtained in 77.3% of the patients, with a complication rate of 13.6%. We concluded that the rectangular flap technique has a simple design, is easily reproducible by in-training staff, has good results, and can be applied on the majority of the syndactyly cases.

Quantitative analysis of collagen and elastic fibers in the transversalis fascia in direct and indirect inguinal hernia

PURPOSE: Our previous studies demonstrated structural and quantitative age-related changes of the elastic fibers in transversalis fascia, which may play a role in inguinal hernia formation. To verify whether there were differences in the extracellular matrix between direct and indirect inguinal hernia, we studied the amount of collagen and elastic fibers in the transversalis fascia of 36 male patients with indirect inguinal hernia and 21 with direct inguinal hernia. MATERIAL AND METHODS: Transversalis fascia fragments were obtained during surgical intervention and underwent histological quantitative analysis of collagen by colorimetry and analysis of elastic fibers by histomorphometry. RESULTS: We demonstrated significantly lower amounts of collagen and higher amounts of elastic fibers in transversalis fascia from patients with direct inguinal hernia compared to indirect inguinal hernia patients. The transversalis fascia from direct inguinal hernia patients showed structural changes of the mature and elaunin elastic fibers, which are responsible for elasticity, and lower density of oxytalan elastic fibers, which are responsible for resistance. These changes promoted loss of resiliency of the transversalis fascia. CONCLUSION: These results improve our understanding of the participation of the extracellular matrix in the genesis of direct inguinal hernia, suggesting a relationship with genetic defects of the elastic fiber and collagen synthesis.

The Stoppa procedure in inguinal hernia repair: to drain or not to drain

OBJECTIVE: The objective of this study is to evaluate the benefits of drainage in the Stoppa procedure for inguinal repair. PATIENTS AND METHODS: The use of a suction drain was randomized at the end of the surgical intervention in 26 male patients undergoing inguinal hernia repair, divided into 2 groups: Group A, 12 patients undergoing drainage, and group B, 14 patients not undergoing drainage. On the second postoperative day, all patients underwent abdominal pelvic computed tomography scan examination to detect the presence of abdominal fluid collection. RESULTS: In group A, no patient developed fluid collection in the preperitoneal space, and 1 patient presented with an abscess in the preperitoneal space on the 15th postoperative day. In group B, 12 patients presented with fluid collections in the preperitoneal space on computed tomography scan evaluation. However, only 3 patients presented minor complications. None of the patients developed a major complication. CONCLUSION: The use of suction drainage with the Stoppa procedure does not provide any benefit.

Incisional hernia at the insertion site of the laparoscopic trocar: case report and review of the literature

Laparoscopic operations offer a myriad of advantages resulting in a rapid postoperative recovery. Incisional hernia is an uncommon cause of morbidity in operative procedures performed by laparoscopic access, and the diagnosis may not be easily made. In our service we identified 2 patients with incisional hernia the site of trocar insertion. The records of these 2 cases were reviewed. We report on these 2 cases and present a review of the literature.

Epigastric pain: incarceration or rotation?

Introduction: Acute intrathoracic gastric volvulus occurs when the stomach has a twist mesenteroaxial/organoaxial or chest cavity resulting in a dilatation or rupture of the diaphragmatic hiatus or diaphragmatic hernia. The purpose of this work is to show a interesting case of gastric volvulus in a patient with several comorbidities. Case Report: A 77-year-old female with past history of hiatal hernia and mental disease associated with diabetes and atrial fibrillation. Patient went to the emergency department due to vomiting associated with blood. Analytical parameters (WBC, HGB, PCR, metabolic panel and liver function), showed no significant alterations. Thoracic X-ray revealed an enlarged mediastinum due to herniation of the stomach. A computed tomography (CT) scan confirmed intrathoracic localization of the gastric antrum with twist. Patient’s symptoms were relieved by nasogastric intubation and analgesia. After six months, the patient is still asymptomatic. Conclusion: In general, the treatment of an acute gastric volvulus requires an emergent surgical repair. In patients who are not surgical candidates (with comorbidities or an inability to tolerate anesthesia), endoscopic reduction should be attempted. Chronic gastric volvulus may be treated non-emergently, and surgical treatment is increasingly being performed using a laparoscopic approach. In this case, it is a chronic form that was solved with the placement of the nasogastric tube. A nasogastric decompression is an option in the chronic form of hiatal hernia associated to gastric volvulus in patients with serious comorbidities.

Scarless laparoscopic repair of epigastric hernia in children

Background Despite the small size of the incision, the scar left by open repair of epigastric hernia in children is unaesthetic. Few laparoscopic approaches to epigastric hernia repair have been previously proposed, but none has gain wide acceptance from pediatric surgeons. In this study, we present our experience with a scarless laparo- scopic approach using a percutaneous suturing technique for epigastric hernia repair in children. Methods Ten consecutive patients presenting with epi- gastric hernia 15 mm or further from the umbilicus were submitted to laparoscopic hernia repair. A 5-mm 308-angle laparoscope is introduced through a umbilical trocar and a 3-mm laparoscopic dissector is introduced through a stab incision in the right flank. After opening and dissecting the parietal peritoneum, the fascial defect is identified and closed using 2–0 polyglactin thread through a percutaneous suturing technique. Intraoperative and postoperative clinical data were collected. Results All patients were successfully submitted to la- paroscopic epigastric hernia repair. Median age at surgery was 79 months old and the median distance from the um- bilicus to the epigastric defect was 4 cm. Operative time ranged from 35 to 75 min. Every hernia was successfully closed without any incidents. Follow-up period ranges from 2 to 12 months. No postoperative complications or recurrence was registered. No scar was visible in these patients. Conclusion This scarless laparoscopic technique for epi- gastric hernia repair is safe and reliable. We believe this technique might become gold standard of care in the near future.

Congenital atresia of the ostium of the left coronary artery. Diagnostic difficulty and successful surgical revascularization in two patients

We report two cases of congenital atresia of the ostium of the left coronary artery. Case 1: a six-month-old infant presenting with serious cardiac insufficiency. A noninvasive diagnosis of dilated myocardiopathy was established and the clinical picture was pharmacologically compensated. When the patient was nine months of age, a hemodynamic study was performed that revealed congenital atresia of the ostium of the left coronary artery; the infant immediately underwent a successful anastomosis of the internal mammary artery with the left coronary artery. Case 2: an eleven-year-old asymptomatic boy with a history of heart murmur from the age of six months on, was refered for surgery with a diagnosis of anomalous origin of the left coronary artery from pulmonary trunk. A definitive diagnosis of atresia of the left coronary ostium was only established during surgery. Successful surgical revascularization with the left internal mammary artery, and left ventricular aneurysmectomy were performed.

Epidemiological characteristics of congenital heart diseases in Londrina, Paraná South Brazil

OBJECTIVE: To determine the prevalence and other epidemiological characteristics of congenital heart diseases. METHODS: A retrospective population based study of children who were born in Londrina, from January '89 to December '98 (80,262 live births). Diagnoses were confirmed through autopsy, surgery, catheterization, or echocardiography. RESULTS: A total of 441 patients was as certained what corresponds to a prevalence of 5.494:1,000 live births. Ventricular septal defect was the commonest lesion. A small number of transpositions of the great vessels and of left ventricular hypoplasia was observed. A high propation of ventricular septal defect (28.3%) and atrioventricular septal defects (8.1%) occurred. Fifty-one (11.35%) affected children had syndromic diseases and 52 (12.01%) children had nonsyndromic anomalies. CONCLUSION: The prevalence of congenital heart diseases in Londrina is in accordance with that of other regions of the globe. This prevalence also may reflect the reality in the southern region of Brazil, because population characteristics are very similar in the 3 southernmost Brazilian states.

Unsupported valvuloplasty in children with congenital mitral valve anomalies. Late clinical results

OBJECTIVE: To analyze late clinical evolution after surgical treatment of children, with reparative and reconstructive techniques without annular support. METHODS: We evaluated 21 patients operated upon between 1975 and 1998. Age 4.67±3.44 years; 47.6% girls; mitral insufficiency 57.1% (12 cases), stenosis 28.6% (6 cases), and double lesion 14.3% (3 cases). The perfusion 43.10±9.50min, and ischemia time were 29.40±10.50min. The average clinical follow-up in mitral insufficiency was 41.52±53.61 months. In the stenosis group (4 patients) was 46.39±32.02 months, and in the double lesion group (3 patients), 39.41±37.5 months. The echocardiographic follow-up was in mitral insufficiency 37.17±39.51 months, stenosis 42.61±30.59 months, and in the double lesion 39.41±37.51 months. RESULTS: Operative mortality was 9.5% (2 cases). No late deaths occurred. In the group with mitral insufficiency, 10 (83.3%) patients were asymptomatic (p=0.04). The majorit y with mild reflux (p=0.002). In the follow-up of the stenosis group, all were in functional class I (NYHA); and the mean transvalve gradient varied between 8 and 12mmHg, average of 10.7mmHg. In the double lesion group, 1 patient was reoperated at 43 months. No endocarditis or thromboembolism were reported. CONCLUSION: Mitral stenosis repair has worse late results, related to the valve abnormalities and associated lesions. The correction of mitral insufficiency without annular support showed good long-term results.