Fernando Amaral

MicroRNAs Differentially Expressed in ACTH-Secreting Pituitary Tumors

CONTEXT MicroRNAs (miRNAs) are small noncoding RNAs, functioning as antisense regulators of gene expression by targeting mRNA and contributing to cancer development and progression. More than 50% of miRNA genes are located in cancer-associated genomic regions or in fragile sites of the genome. OBJECTIVE The aim of the study was to analyze the differential expression of let-7a, miR-15a, miR-16, miR-21, miR-141, miR-143, miR-145, and miR-150 in corticotropinomas and normal pituitary tissue and verify whether their profile of expression correlates with tumor size or remission after treatment. MATERIAL AND METHODS ACTH-secreting pituitary tumor samples were obtained during transphenoidal surgery from patients with Cushing disease and normal pituitary tissues from autopsies. The relative expression of miRNAs was measured by real-time PCR using RNU44 and RNU49 as endogenous controls. Relative quantification of miRNA expression was calculated using the 2(-DeltaDeltaCt) method. RESULTS We found underexpression of miR-145 (2.0-fold; P = 0.04), miR-21 (2.4-fold; P = 0.004), miR-141 (2.6-fold; P = 0.02), let-7a (3.3-fold; P = 0.003), miR-150 (3.8-fold; P = 0.04), miR-15a (4.5-fold; P = 0.03), miR-16 (5.0-fold; P = 0.004), and miR-143 (6.4-fold; P = 0.004) in ACTH-secreting pituitary tumors when compared to normal pituitary tissues. There were no differences between miRNA expression and tumor size as well as miRNA expression and ratio of remission after surgery, except in patients presenting lower miR-141 expression who showed a better chance of remission. CONCLUSION Our results support the possibility that altered miRNA expression profile might be involved in corticotrophic tumorigenesis. However, the lack of knowledge about miRNA target genes postpones full understanding of the biological functions of down-regulated or up-regulated miRNAs in corticotropinomas.

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 referred 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.

Cardiopatia congênita no adulto: perfil clínico ambulatorial no Hospital das Clínicas de Ribeirão Preto

BACKGROUND: Service experiences for adults with congenital heart disease have not been reported in our country. OBJECTIVE: To describe the basic clinical profile of adults with congenital heart disease in an outpatient tertiary care center. METHODS: We compiled data on age, gender, place of residence, primary diagnosis, and secondary diagnoses of 413 patients treated for seven years. RESULTS: G1 (untreated): 195 patients, 51% women, 57% between 14 and 30 years, 80% living in the region. The most frequent heart diseases were ventricular septal defect (VSD) (31%), atrial septal defect (ASD) (29%), and pulmonary stenosis (7%). The predominant secondary diagnoses were hypertension (9%) and arrhythmias (5%). G2 (treated): 218 patients, 56% women, 57% between 14 and 30 years, 81% living in the region. The most frequently treated heart diseases were: ASD (36%), tetralogy of Fallot (14%), coarctation of the aorta (12%), and VSD (11%). Sixty-nine (32%) patients were operated on for congenital heart diseases in adulthood. Sixteen (7%) underwent an interventional catheterization. The predominant secondary diagnoses were hypertension (18%) and arrhythmias (8%). CONCLUSION: In the study, most patients were treated invasively, all of them were residents in the region, and most of them were under 40 years of age. Defects such as ASD, VSD, and pulmonary stenosis predominated in the untreated group, whereas in the treated group, most patients had undergone surgical correction of ASD, tetralogy of Fallot, aortic coarctation, and VSD. Hypertension and arrhythmias were relevant in both groups, and a large variety of other comorbidities were also observed.

Deficiência da 11beta-hidroxilase

Congenital adrenal hyperplasia due to 11beta-hydroxylase enzyme deficiency is a result of the impairment of 11-deoxycortisol to cortisol conversion. In general, it is responsible for less than 5% of the congenital adrenal hyperplasia cases. The clinical expression of androgen excess in females includes several degrees of genital ambiguity, varying from clitoromegaly to complete virilization. Due to the accumulation of mineralocorticoids, approximately 50% of the patients develop blood hypertension. Mutations in the CYP11B1 gene are responsible for the disease. Biochemical and molecular characteristics of the enzyme and their implications in the clinical presentation of 11beta-hydroxylase deficiency are reviewed here.

Anomalous origin of the left pulmonary artery from the ascending aorta: successful surgical correction in an infant with fallot's tetralogy

We describe the case of a 40-day-old female patient with a history of breathlessness since birth who was referred to our hospital for surgical correction of common arterial trunk. The invasive investigation disclosed a Fallot cent s tetralogy anatomy associated with an anomalous origin of the left pulmonary artery from the ascending aorta. Immediately after diagnosis, the patient underwent a successful total surgical correction of the defect, including simultaneous anastomosis of the left pulmonary artery to the pulmonary trunk.

Cardiologic evaluation of children with suspected heart disease: experience of a public outpatient clinic in Brazil

CONTEXT During initial evaluation of children on an outpatient basis, the index of suspected heart disease may be high, particularly if we consider that innocent murmur occurs in about 50% of the pediatric population. This is the most common cause of referral to the pediatric cardiologist. OBJECTIVE To report on the experience of a public outpatient clinic in the southeastern region of Brazil. DESIGN Retrospective analysis of all patients submitted to cardiologic evaluation within a 39 month period. SETTING Public pediatric cardiology outpatient clinic. PARTICIPANTS 2675 consecutive children aged</=15 years referred from the local and regional basic health units due to suspected heart disease. MAIN MEASUREMENTS Reason for referral, diagnostic investigation, final diagnosis based on the reason for referral, therapeutic procedures. RESULTS The main reasons for referral were: murmur (70%), precordial pain (9%), suspicion of arrhythmia (9%) and breathlessness (5%). Of the total number, 695 cases (26%) did not complete the investigation and were not included in the analysis. A final diagnosis was obtained based on the reason for referral and the main conclusions were: l) a high incidence of normality was found: murmur (83%), pain (98%), arrhythmia (97%) and breathless (94%); 2) heart disease was unlikely, based on other referral reasons; 3) 14% of the children were considered abnormal and 1% needed therapeutical procedures. CONCLUSIONS The establishment of a pediatric cardiology outpatient clinic within the public health service in the region seems to be justifiable, due to the high current demand. The low global incidence of heart disease, with a high prevalence of children with innocent murmur, discloses the need for a specific training program in cardiology for pediatricians.

SAGE analysis highlights the putative role of underexpression of ribosomal proteins in GH-secreting pituitary adenomas.

BACKGROUND Although the molecular pathogenesis of pituitary adenomas has been assessed by several different techniques, it still remains partially unclear. Ribosomal proteins (RPs) have been recently related to human tumorigenesis, but they have not yet been evaluated in pituitary tumorigenesis. OBJECTIVE The aim of this study was to introduce serial analysis of gene expression (SAGE), a high-throughput method, in pituitary research in order to compare differential gene expression. METHODS Two SAGE cDNA libraries were constructed, one using a pool of mRNA obtained from five GH-secreting pituitary tumors and another from three normal pituitaries. Genes differentially expressed between the libraries were further validated by real-time PCR in 22 GH-secreting pituitary tumors and in 15 normal pituitaries. RESULTS Computer-generated genomic analysis tools identified 13,722 and 14,993 exclusive genes in normal and adenoma libraries respectively. Both shared 6497 genes, 2188 were underexpressed and 4309 overexpressed in tumoral library. In adenoma library, 33 genes encoding RPs were underexpressed. Among these, RPSA, RPS3, RPS14, and RPS29 were validated by real-time PCR. CONCLUSION We report the first SAGE library from normal pituitary tissue and GH-secreting pituitary tumor, which provide quantitative assessment of cellular transcriptome. We also validated some downregulated genes encoding RPs. Altogether, the present data suggest that the underexpression of the studied RP genes possibly collaborates directly or indirectly with other genes to modify cell cycle arrest, DNA repair, and apoptosis, leading to an environment that might have a putative role in the tumorigenesis, introducing new perspectives for further studies on molecular genesis of somatotrophinomas.

Initial diagnostic errors in children suspected of having heart disease: prevalence and long-term consequences

OBJECTIVE To access the incidence of diagnostic errors in the initial evaluation of children with cardiac murmurs. METHODS We evaluated our 7-years of experience in a public pediatric cardiology outpatient clinic. Of 3692 patients who were sent to the hospital, 2603 presented with a heart murmur and were investigated. Patients for whom a disagreement existed between the initial and final diagnoses were divided into the following 2 groups: G1 (n=17) with an initial diagnosis of an innocent murmur and a final diagnosis of cardiopathy, and G2 (n=161) with an initial diagnosis of cardiopathy and a final diagnosis of a normal heart. RESULTS In G1, the great majority of patients had cardiac defects with mild hemodynamic repercussions, such as small ventricular septal defect and mild pulmonary stenosis. In G2, the great majority of structural defects were interventricular communication, atrial septal defect and pulmonary valve stenosis. CONCLUSION A global analysis demonstrated that diagnostic error in the initial evaluation of children with cardiac murmurs is real, reaching approximately 6% of cases. The majority of these misdiagnoses were in patients with an initial diagnosis of cardiopathy, which was not confirmed through later complementary examinations. Clinical cardiovascular examination is an excellent resource in the evaluation of children suspected of having cardiopathy. Immediate outpatient discharge of children with an initial diagnosis of an innocent heart murmur seems to be a suitable approach.

Desmoid Tumor After a Minimally Invasive Atrial Septal Defect Closure in an Adolescent

The surgical closure of secundum atrial septal defect (ASD) is frequently performed. The minimally invasive approach, currently adopted by many centers as a way to preserve aesthetic appearance, particularly in female patients, seems to be safe. We describe the case of an adolescent who developed a desmoid tumor soon after a minimally invasive operation for surgical closure of a secundum ASD.

Profile of pediatric outpatient in cardiology clinics in the city of Ribeirão Preto

OBJECTIVE To verify the pediatric cardiology outpatient clinic characteristics in Ribeirão Preto (RP) city, emphasizing reasons for referral, definitive diagnosis and outcome through analysis of patients seen in 3 distinct settings. METHODS In 1996, 1,365 consecutive patients, aged 1 month to 14 years were seen: G1 (n = 562), public pediatric cardiology outpatient clinic; G2 (n = 420), private practice; G3 (n = 383) pediatric cardiology outpatient clinic at Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto. Origin of the patients: G1: RP (78%) and region (22%); G2: RP (67%), region (25%), and other regions/states (8%); G3: RP (26%), region (43.5%), and other regions/states (30.5%). RESULTS Reasons for referral: G1: murmur (71%), arrhythmia (8%), chest pain (7%), breathlessness (6.5%), other reasons (7.5%). G2: murmur (70%), chest pain (7%), arrhythmia (7%), breathlessness (4%), postoperative follow-up (4%), other reasons (8%). G3: murmur (56%), postoperative follow-up (24%), arrhythmia (4%), other reasons (16%). Patients lost to follow-up: G1: 31%, G2: 17%, G3: 3%. FINAL DIAGNOSIS G1: 346 (89%) normal and 43 (11%) abnormal patients; G2: 268 (76%) normal and 82 (24%) abnormal patients; G3: 22 (6%) normal and 351 (94%) abnormal patients. OUTCOME G1: discharge (89%), follow-up (11%); G2: discharge (76%), follow-up (24%); G3: discharge (6%), follow-up (94%). CONCLUSION Clinical profile is different among the 3 groups (G1 and G2 are similar). Intervention in the Basic Health Units seems to be necessary to verify structural facilities and to offer basic pediatric cardiology training to pediatricians. It is important to verify the high index of patients lost to follow-up, particularly in G1. Structural and human resources are needed if adequate assistance is to be expected for the highly complex cases seen in G3. The pediatric cardiology public outpatient clinic should be maintained until resolution of cases by the pediatricians in the Basic Health Units improves.