IS -94INS/DELATTG POLYMORPHISM IN THE NUCLEAR FACTOR KAPPA-B1 GENE (NFKB1) ASSOCIATED WITH NECROTIZING ENTEROCOLITIS?

BACKGROUND: Abnormalities in the different stages of the intestinal maturation process cause metabolic and molecular changes. Among the genetic alterations associated with necrotizing enterocolitis, the -94ins/delATTG polymorphism in NFKB1 gene leads to unregulated activation of the NFKB protein due to an increase in the inherent pro-inflammatory state of the premature intestine. AIMS: To determine the prevalence of the -94ins/delATTG polymorphism in NFKB1 gene in neonates with and without necrotizing enterocolitis. METHODS: This is a case-control study, in which 25 neonates were evaluated as the case group and 50 neonates as the control group, of both genders. DNA was extracted from peripheral blood leukocytes, and the site encompassing the polymorphism was amplified by molecular techniques (polymerase chain reaction/polymorphism in restriction fragment length). RESULTS: Necrotizing enterocolitis was diagnosed in 25 (33%) neonates and, of these, 3 (12%) died. Male gender was more prevalent in both groups (p=0.1613): cases (52%) and controls (62%). Moderate and extreme preterm newborns were predominant in both groups: cases (80%) and controls (88%) (p=0.3036). Low birth weight and extremely low birth weight newborns were the most prevalent in cases (78%), and very low birth weight and extremely low birth weight were the most prevalent in controls (81%) (p=0.1073). Clinical treatment was successful in 72%, and hospital discharge was achieved in 88% of newborns with NEC. The -94ins/delATTG polymorphism in NFKB1 gene was not identified in all the 150 alleles analyzed (100%). CONCLUSIONS: The absence of the -94ins/delATTG polymorphism in NFKB1 gene in newborns with and without necrotizing enterocolitis does not rule out the possibility of alterations in this and/or in other genes in newborns with this condition, which reinforces the need for further research.

DOES SLC11A2 GENE MUTATION ASSOCIATE WITH IRON-REFRACTORY IRON-DEFICIENCY ANEMIA AFTER BARIATRIC SURGERY?

AIM: After bariatric surgery, if there is iron-refractory iron-deficiency anemia (IRIDA) and does not respond to supplemental iron therapy, excluding other possible etiologies, genetic changes involved in iron metabolism should be considered. This study aimed to investigate the association of both mutations 1285G-C and 1246C-T, in the SLC11A2 gene, and the etiopathogenesis of anemia refractory to iron supplementation in patients undergoing bariatric surgery using Roux-en-Y gastric bypass (RYGB). METHODS: A case-control study was conducted, in which 100 patients were evaluated as Cases Group [subdivided into (i) with Anemia and (ii) without Anemia] and 100 individuals as Controls, comprising both sexes. Inherited and acquired causes of IRIDA were excluded. DNA was extracted from leukocytes of peripheral blood, and the regions that cover both mutations have been amplified by the molecular techniques such as polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The 1285G-C mutation was not determined in any of the 400 alleles analyzed. Regarding the 1246C-T mutation, the wild CC genotype was found with a higher prevalence in the Control Group (34%) (OR 0.5475; 95%CI 0.2920-1.027; p=0.0827). The mutant TT genotype was found only in the Cases Group I (with Anemia) (13%). CONCLUSION: The results show the association between 1246C-T mutation, in the SLC11A2 gene, and the etiopathogenesis of IRIDA to iron supplementation in the evaluated sample. There are differences, at the molecular level, in patients with and without IRIDA after bariatric surgery using RYGB.

Relationship between Serotonin-2A Receptor Gene Polymorphism and Wound Healing in Brazilian Patients

Abstract Genetic changes in platelet serotonin receptors (5-HTR2A) impair the initial process of tissue repair, regardless of the triggering factor of the skin wound. Objective was to determine the prevalence of the 102T-C polymorphism in the 5-HTR2A gene in Brazilian patients with and without skin wounds. Cross-sectional case-control study, in which 100 patients were evaluated as Cases Group (subdivided into I-with Chronic Wound and II-with Acute Wound) and 100 individuals as Controls, of both genders. DNA was extracted from leukocytes of peripheral blood and the region that covers the polymorphism was amplified by the molecular techniques Polymerase Chain Reaction/Restriction Fragment Length Polymorphism. The TT genotype was significantly associated with the protective factor against alterations in the healing process of skin wounds (OR: 0.4833; 95%CI: 0.2704-0.8638; p<0.05) in the Control Group. The genotypic analysis between Cases Group (I-Chronic Wound and II-Acute Wound) determined that the TT genotype was significantly associated with the protection factor in Case II (OR: 0.3333; 95%CI: 0.1359-0.8177; p<.005) and the CC genotype was significantly associated with the chance to develop chronic ulcers in the Case I (OR: 6.667; 95%CI: 1.801-24.683; p<0.05). Patients with chronic skin wounds have a higher prevalence of the 102T-C polymorphism in the 5-HTR2A gene, which is associated to alterations in the healing process in this population. There are differences, at the molecular level, in patients, with and without these lesions, and the probable role of the serotonergic system in wound healing.

A mutação do gene SLC11A2 está associada à anemia por deficiência de ferro refratária após cirurgia bariátrica? / Does slc11a2 gene mutation associate with iron-refractory iron-deficiency anemia after bariatric surgery?

ABSTRACT - BACKGROUND: After bariatric surgery, if there is iron-refractory iron-deficiency anemia (IRIDA) and does not respond to supplemental iron therapy, excluding other possible etiologies, genetic changes involved in iron metabolism should be considered. AIM: This study aimed to investigate the association of both mutations 1285G-C and 1246C-T, in the SLC11A2 gene, and the etiopathogenesis of anemia refractory to iron supplementation in patients undergoing bariatric surgery using Roux-en-Y gastric bypass (RYGB). METHODS: A case-control study was conducted, in which 100 patients were evaluated as Cases Group [subdivided into (i) with Anemia and (ii) without Anemia] and 100 individuals as Controls, comprising both sexes. Inherited and acquired causes of IRIDA were excluded. DNA was extracted from leukocytes of peripheral blood, and the regions that cover both mutations have been amplified by the molecular techniques such as polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The 1285G-C mutation was not determined in any of the 400 alleles analyzed. Regarding the 1246C-T mutation, the wild CC genotype was found with a higher prevalence in the Control Group (34%) (OR 0.5475; 95%CI 0.2920-1.027; p=0.0827). The mutant TT genotype was found only in the Cases Group I (with Anemia) (13%). CONCLUSION: The results show the association between 1246C-T mutation, in the SLC11A2 gene, and the etiopathogenesis of IRIDA to iron supplementation in the evaluated sample. There are differences, at the molecular level, in patients with and without IRIDA after bariatric surgery using RYGB.

RESUMO - RACIONAL: Após cirurgia bariátrica, se houver anemia por deficiência de ferro e não responder à terapia de ferro suplementar, excluindo-se outras possíveis etiologias, alterações genéticas envolvidas no metabolismo férrico devem ser consideradas. OBJETIVO: Investigar a associação das mutações 1285G-C e 1246C-T, no gene SLC11A2, e a etiopatogênese da anemia refratária à suplementação de ferro em pacientes submetidos à cirurgia bariátrica pela técnica de derivação gástrica em Y-de-Roux. MÉTODOS: Estudo de caso-controle, no qual forma avaliados 100 pacientes em Grupos de Casos (subdividido em Grupo I - com Anemia e Grupo II - sem Anemia) e 100 indivíduos como Controles, de ambos os sexos. Causas hereditárias e adquiridas de anemia ferropriva refratária ao ferro, foram excluídas. O DNA foi extraído de leucócitos de sangue periférico e as regiões que abrangem ambas as mutações foram amplificadas pelas técnicas moleculares de Reação em Cadeia da Polimerase/Polimorfismo do Comprimento do Fragmento de Restrição. RESULTADOS: A mutação 1285G-C não foi determinada em quaisquer dos 400 alelos analisados. Em relação à mutação 1246C-T, o genótipo homozigoto selvagem CC foi encontrado com maior prevalência nos Controles (34%) (OR: 0,5475; 95%IC: 0,2920-1,027; p=0,0827). O genótipo homozigoto mutante TT foi encontrado apenas no Grupo I - com Anemia (13%). CONCLUSÃO: Os resultados demonstram a associação da mutação 1246C-T, no gene SLC11A2, e a etiopatogênese da anemia ferropriva refratária e persistente à suplementação de ferro, nesta amostra de pacientes. Há diferenças, em nível molecular, em pacientes com e sem anemia ferropriva refratária ao ferro após cirurgia bariátrica por derivação gástrica em Y-de-Roux.

Is -94ins/delattg polymorphism in the nuclear factor kappa-b1 gene (nfkb1) associated with necrotizing enterocolitis? / Polimorfismo -94ins/delattg no gene do fator nuclear kappa-b1 (nfkb1) está associado à enterocolite necrosante?

ABSTRACT BACKGROUND: Abnormalities in the different stages of the intestinal maturation process cause metabolic and molecular changes. Among the genetic alterations associated with necrotizing enterocolitis, the -94ins/delATTG polymorphism in NFKB1 gene leads to unregulated activation of the NFKB protein due to an increase in the inherent pro-inflammatory state of the premature intestine. AIMS:To determine the prevalence of the -94ins/delATTG polymorphism in NFKB1 gene in neonates with and without necrotizing enterocolitis. METHODS:This is a case-control study, in which 25 neonates were evaluated as the case group and 50 neonates as the control group, of both genders. DNA was extracted from peripheral blood leukocytes, and the site encompassing the polymorphism was amplified by molecular techniques (polymerase chain reaction/polymorphism in restriction fragment length). RESULTS:Necrotizing enterocolitis was diagnosed in 25 (33%) neonates and, of these, 3 (12%) died. Male gender was more prevalent in both groups (p=0.1613): cases (52%) and controls (62%). Moderate and extreme preterm newborns were predominant in both groups: cases (80%) and controls (88%) (p=0.3036). Low birth weight and extremely low birth weight newborns were the most prevalent in cases (78%), and very low birth weight and extremely low birth weight were the most prevalent in controls (81%) (p=0.1073). Clinical treatment was successful in 72%, and hospital discharge was achieved in 88% of newborns with NEC. The -94ins/delATTG polymorphism in NFKB1 gene was not identified in all the 150 alleles analyzed (100%). CONCLUSIONS:The absence of the -94ins/delATTG polymorphism in NFKB1 gene in newborns with and without necrotizing enterocolitis does not rule out the possibility of alterations in this and/or in other genes in newborns with this condition, which reinforces the need for further research.

RESUMO RACIONAL:Anormalidades nas diferentes fases do processo de maturação intestinal causam alterações metabólicas e moleculares. Dentre as alterações genéticas associadas à enterocolite necrotizante, o polimorfismo -94ins/delATTG no gene NFKB1 leva à ativação desregulada da proteína NFKB devido ao aumento do estado pró-inflamatório inerente ao intestino prematuro. OBJETIVOS:Determinar a prevalência do polimorfismo -94ins/delATTG no gene NFKB1 em neonatos com e sem enterocolite necrotizante. MÉTODOS: Trata-se de um estudo caso-controle, no qual foram avaliados 25 neonatos como grupo caso e 50 neonatos como grupo controle, de ambos os sexos. O DNA foi extraído de leucócitos do sangue periférico e o sítio que engloba o polimorfismo foi amplificado por técnicas moleculares (reação em cadeia da polimerase/polimorfismo no comprimento do fragmento de restrição). RESULTADOS: Enterocolite necrosante foi diagnosticada em 25 (33%) neonatos e, destes, 3 (12%) foram a óbito. O gênero masculino foi mais prevalente em ambos os grupos (p=0,1613): casos (52%) e controles (62%). Os prematuros moderados e extremos foram predominantes em ambos os grupos: casos (80%) e controles (88%) (p=0,3036). Recém-nascidos de baixo peso e extremo baixo peso foram os mais prevalentes nos casos (78%) e de muito baixo peso e extremo baixo peso foram os mais prevalentes nos controles (81%) (p=0,1073). O tratamento clínico foi bem-sucedido em 72% e a alta hospitalar foi obtida em 88% dos recém-nascidos com enterocolite necrotizante. O polimorfismo -94ins/delATTG no gene NFKB1 não foi identificado em todos os 150 alelos analisados (100%). CONCLUSÕES: A ausência do polimorfismo -94ins/delATTG no gene NFKB1 em recém-nascidos com e sem enterocolite necrosante não afasta a possibilidade de alterações neste e/ou em outros genes em recém-nascidos com esta condição, o que reforça a necessidade de novas pesquisas.

Leucomalácia periventricular e correlação com citocinas pro e antiinflamatórias / Periventricular leukomalacia and correlation with pro and anti-inflammatory cytokines

Introdução:Polimorfismos em genes de citocinas inflamatórias (TNF-α e IL-1ß) e antiinflamatórias (IL-10) intensificam a resposta inflamatória, após anóxia, aumentando as afecções decorrentes da síndrome hipóxico-isquêmica como a leucomalácia periventricular (LPV). Objetivos: Investigar a associação entre ambos os polimorfismos inflamatórios (-1031T/C no gene TNF-α e -511C/T no gene IL-1ß) e o antiinflamatório (-1082G/A no gene IL-10) e a etiopatogênese/risco da LPV em neonatos com esta afecção. Material e Métodos: Estudo prospectivo de casos-controle em 50 neonatos prematuros e a termo (Grupo Casos) e em 50 neonatos a termo (Grupo Controle), de ambos os sexos. DNA foi extraído de leucócitos de sangue periférico e a análise molecular realizada pela Reação em Cadeia da Polimerase/Análise de Restrição Enzimática (PCR/RFLP). Resultados: A idade gestacional média entre casos e controles foi, respectivamente, de 31,0 semanas e 39,4 semanas (p<0,0001). O peso médio, em gramas, foi de 1561,1 para os casos e 3509,9 para controles (p<0,0001). Foi encontrada associação entre o genótipo TC (produtor intermediário de citocina inflamatória) (OR: 2.495; IC95%: 1,10-5,63; p=0,043) assim como entre os genótipos TC+CC (produtores inflamatórios intermediário+alto) (OR: 2,471; IC95%: 1,10-5,55; p=0,044) no gene TNF-α e o risco de LPV. Estatisticamente significante associação foi encontrada entre os genótipos (CT+TT) (produtores inflamatórios intermediário+alto) (OR: 23,120; IC95%: 1,31-409,4; p=0,003) no gene IL-1ß e o risco de LPV. No gene IL-10, foi encontrada reduçãosignificativa do risco de LPV para o genótipo GG (alto produtor antiinflamatório) (OR: 0,07407; IC95%: 0,02-0,34; p<0,0001)assim como para o alelo G (OR: 0,5098; IC95%: 0,29-0,91; p=0,030). Conclusão: há associação entre os polimorfismosinflamatórios (-1031T/C no gene TNF-α e -511C/T no gene IL-1ß) e o risco de desenvolvimento de LPV e associação entre opolimorfismo antiinflamatório (-1082G/A no gene IL-10) na proteção ao desenvolvimento da LPV, na população estudada.

The association between pro- and anti-inflammatory cytokine polymorphisms and periventricular leukomalacia in newborns with hypoxic-ischemic encephalopathy.

BACKGROUND: Periventricular leukomalacia (PVL) is a frequent consequence of hypoxic-ischemic injury. Functional cytokine gene variants that result in altered production of inflammatory (tumor necrosis factor-alpha [TNF-α] and interleukin-1beta [IL-1ß]) or anti-inflammatory (interleukin-10 [IL-10]) cytokines may modify disease processes, including PVL. OBJECTIVE: The aim of this study was to evaluate if there is a relationship between the two proinflammatory polymorphisms (TNF-α-1031T/C and IL-1ß-511C/T) and the anti-inflammatory polymorphism IL-10-1082G/A and PVL risk in Brazilian newborns with and without this injury. MATERIALS AND METHODS: A cross-sectional case-control study performed at the Neonatal Intensive Care Unit of the Children's Hospital and Maternity of the São José do Rio Preto Medical School (FAMERP). Fifty preterm and term newborns were examined as index cases and 50 term newborns as controls, of both sexes for both groups. DNA was extracted from peripheral blood leukocytes, and the sites that encompassed the three polymorphisms were amplified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Gestational age ranged from 25 to 39 weeks, in the case group, and in the control group it ranged from 38 to 42.5 weeks (P<0.0001). Statistically significant association was found between TNF-α-1031T/C high expression genotype TC (odds ratio [OR], 2.495; 95% confidence interval [CI], 1.10-5.63; P=0.043) as well as between genotypes (TC + CC) (OR, 2.471; 95% CI, 1.10-5.55; P=0.044) and risk of PVL. Statistically significant association was found between IL-1ß-511C/T high expression genotypes (CT + TT) (OR, 23.120; 95% CI, 1.31-409.4; P=0.003) and risk of PVL. Statistically significant association between IL-10-1082G/A high expression genotype GG (OR, 0.07407; 95% CI, 0.02-0.34; P<0.0001) as well as between IL-10-1082G high expression allele (OR, 0.5098; 95% CI, 0.29-0.91; P=0,030) and PVL reduced risk was observed. There was a statistically significant association between TC/CT/GA genotype combination and the risk of PVL (OR, 6.469; 95% CI, 2.00-20.92; P=0.001). CONCLUSION: There is evidence of an association between the polymorphisms TNF-α-1031T/C, IL-1ß-511C/T, and IL-10-1082G/A and PVL risk in this Brazilian newborn population studied.

Molecular approach of auditory neuropathy / Abordagem molecular da neuropatia auditiva

INTRODUCTION: Mutations in the otoferlin gene are responsible for auditory neuropathy. OBJECTIVE: To investigate the prevalence of mutations in the mutations in the otoferlin gene in patients with and without auditory neuropathy. METHODS: This original cross-sectional case study evaluated 16 index cases with auditory neuropathy, 13 patients with sensorineural hearing loss, and 20 normal-hearing subjects. DNA was extracted from peripheral blood leukocytes, and the mutations in the otoferlin gene sites were amplified by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The 16 index cases included nine (56%) females and seven (44%) males. The 13 deaf patients comprised seven (54%) males and six (46%) females. Among the 20 normal-hearing subjects, 13 (65%) were males and seven were (35%) females. Thirteen (81%) index cases had wild-type genotype (AA) and three (19%) had the heterozygous AG genotype for IVS8-2A-G (intron 8) mutation. The 5473C-G (exon 44) mutation was found in a heterozygous state (CG) in seven (44%) index cases and nine (56%) had the wild-type allele (CC). Of these mutants, two (25%) were compound heterozygotes for the mutations found in intron 8 and exon 44. All patients with sensorineural hearing loss and normal-hearing individuals did not have mutations (100%). CONCLUSION: There are differences at the molecular level in patients with and without auditory neuropathy. .

INTRODUÇÃO: Mutações no gene da otoferlina (OTOF) são responsáveis pela neuropatia auditiva. OBJETIVO: Investigar a prevalência de mutações no gene OTOF em pacientes com e sem neuropatia auditiva. MÉTODO: Estudo de casos em corte transversal sendo avaliados 16 casos índice com neuropatia auditiva, 13 pacientes com deficiência auditiva sensorioneural (DASN) e 20 indivíduos ouvintes. DNA foi extraído de leucócitos do sangue periférico e regiões do gene OTOF foram analisadas pela técnica PCR-RFLP. RESULTADOS: Dos 16 casos índice, 9 (56%) são do gênero feminino e 7 (44%) do masculino. Dos 13 pacientes com DASN, 7 (54%) são masculinos e 6 (46%) femininos. Dos 20 ouvintes, 13 (65%) são masculinos e 7 (35%) femininos. Treze (81%) casos índice apresentam o genótipo selvagem (AA) e 3 (19%) o genótipo heterozigoto AG para a mutação IVS8-2A-G (intron 8). A mutação 5473C-G (exon 44) foi encontrada em heterozigose (CG) em 7 (44%) dos casos índice e 9 (56%) apresentam o genótipo selvagem (CC). Destes mutantes, dois (25%) são heterozigotos compostos para as mutações encontradas no intron 8 e exon 44. Os pacientes com DASN e os ouvintes não apresentam mutações (100%). CONCLUSÃO: Existem diferenças, ao nível molecular, em pacientes com e sem neuropatia audi tiva. .

Molecular approach of auditory neuropathy.

INTRODUCTION: Mutations in the otoferlin gene are responsible for auditory neuropathy. OBJECTIVE: To investigate the prevalence of mutations in the mutations in the otoferlin gene in patients with and without auditory neuropathy. METHODS: This original cross-sectional case study evaluated 16 index cases with auditory neuropathy, 13 patients with sensorineural hearing loss, and 20 normal-hearing subjects. DNA was extracted from peripheral blood leukocytes, and the mutations in the otoferlin gene sites were amplified by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The 16 index cases included nine (56%) females and seven (44%) males. The 13 deaf patients comprised seven (54%) males and six (46%) females. Among the 20 normal-hearing subjects, 13 (65%) were males and seven were (35%) females. Thirteen (81%) index cases had wild-type genotype (AA) and three (19%) had the heterozygous AG genotype for IVS8-2A-G (intron 8) mutation. The 5473C-G (exon 44) mutation was found in a heterozygous state (CG) in seven (44%) index cases and nine (56%) had the wild-type allele (CC). Of these mutants, two (25%) were compound heterozygotes for the mutations found in intron 8 and exon 44. All patients with sensorineural hearing loss and normal-hearing individuals did not have mutations (100%). CONCLUSION: There are differences at the molecular level in patients with and without auditory neuropathy.

Gradual approach to refinement of the nasal tip: surgical results / Abordagem gradativa para refinamento da ponta nasal: resultados cirúrgicos

Introduction: The complexity of the nasal tip structures and the impact of surgical maneuvers make the prediction of the final outcome very difficult. Therefore, no single technique is enough to correct the several anatomical presentations, and adequate preoperative planning represents the basis of rhinoplasty. Objective: To present results of rhinoplasty, through the gradual surgical approach to nasal tip definition based on anatomical features, and to evaluate the degree of patient satisfaction after the surgical procedure. Methods: Longitudinal retrospective cohort study of the medical charts of 533 patients of both genders who underwent rhinoplasty from January of 2005 to January of 2012 was performed. Cases were allocated into seven groups: (1) no surgery on nasal tip; (2) interdomal breakup; (3) cephalic trim; (4) domal suture; (5) shield-shaped graft; (6) vertical dome division; (7) replacement of lower lateral cartilages. Results: Group 4 was the most prevalent. The satisfaction rate was 96% and revision surgery occurred in 4% of cases. Conclusion: The protocol used allowed the implementation of a gradual surgical approach to nasal tip definition with the nasal anatomical characteristics, high rate of patient satisfaction with the surgical outcome, and low rate of revision. .

Introdução: A complexidade das estruturas da ponta nasal e o impacto de manobras cirúrgicas sobre o seu suporte dificultam a previsão da forma final da mesma. Devido a isso, nenhuma técnica isolada é suficiente para corrigir adequadamente as numerosas apresentações anatômicas, sendo o planejamento pré-operatório, a base da rinoplastia. Objetivos: Apresentar resultados de rinoplastias, por meio da abordagem cirúrgica gradativa para definição da ponta nasal baseada nas características anatômicas, e avaliar o grau de satisfação dos pacientes após a realização do procedimento cirúrgico. Método: Estudo em coorte histórica longitudinal no qual foram avaliados os prontuários de 533 pacientes de ambos os gêneros submetidos à rinoplastia no período de Janeiro de 2005 a Janeiro de 2012. Os pacientes foram divididos em sete grupos: (1) Nenhuma cirurgia na ponta nasal;( 2) Divulsão interdomal; (3) Ressecção cefálica; (4) Sutura domal; (5) Enxerto em escudo; (6) Divisão vertical dos domus; (7) Reconstrução das cartilagens alares maiores. Resultados: O grupo 4 foi o de maior prevalência. A taxa de satisfação foi de 96% e a revisão cirúrgica ocorreu em 4% dos casos. Conclusão: O protocolo utilizado permitiu a associação da abordagem cirúrgica gradativa para definição da ponta nasal com as características anatômicas nasais, alta taxa de satisfação como resultado cirúrgico e baixa taxa de revisão. .

Gradual approach to refinement of the nasal tip: surgical results.

INTRODUCTION: The complexity of the nasal tip structures and the impact of surgical maneuvers make the prediction of the final outcome very difficult. Therefore, no single technique is enough to correct the several anatomical presentations, and adequate preoperative planning represents the basis of rhinoplasty. OBJECTIVE: To present results of rhinoplasty, through the gradual surgical approach to nasal tip definition based on anatomical features, and to evaluate the degree of patient satisfaction after the surgical procedure. METHODS: Longitudinal retrospective cohort study of the medical charts of 533 patients of both genders who underwent rhinoplasty from January of 2005 to January of 2012 was performed. Cases were allocated into seven groups: (1) no surgery on nasal tip; (2) interdomal breakup; (3) cephalic trim; (4) domal suture; (5) shield-shaped graft; (6) vertical dome division; (7) replacement of lower lateral cartilages. RESULTS: Group 4 was the most prevalent. The satisfaction rate was 96% and revision surgery occurred in 4% of cases. CONCLUSION: The protocol used allowed the implementation of a gradual surgical approach to nasal tip definition with the nasal anatomical characteristics, high rate of patient satisfaction with the surgical outcome, and low rate of revision.

Molecular pathogenesis of juvenile nasopharyngeal angiofibroma in brazilian patients.

Juvenile nasopharyngeal angiofibroma (JNA) is a vascular tumor of the nasopharynx that accounts for 0.5% of all cancers of the head and neck. It primarily affects males aged 14-25 years. Of the many genes that mediate the development of JNA, GSTM1 has been most frequently associated with this vascular tumor. The loss of expression of GSTM1 (null genotype) is linked to the development of these tumors. The aim of this cross-sectional case study was to examine the prevalence of the GSTM1-null genotype in Brazilian patients with JNA. DNA was extracted from the leukocytes of blood samples from 10 patients. GSTM1 genotypes were analyzed using a PCR-based assay that was designed to identify the wild-type allele of GSTM1. All 10 patients (100%) were males, with a mean age of 17.8 years. The null genotype for GSTM1 was noted in 4 patients (40%)-1 (10%) at Fisch stage I, 1 (10%) at stage III, and 2 (20%) at stage II. No patient with this genotype had stage IV disease. There was no correlation between Fisch classification and GSTM1 genotype (P = .5695). The correlation between age at diagnosis and GSTM1 genotype was not significant (P = .728). The present findings indicate that there is evidence of an association between the GSTM1-null genotype and JNA in this studied Brazilian population.

Relationship of obstructive sleep apnea syndrome with the 5-HT2A receptor gene in Brazilian patients.

BACKGROUND: Serotonin (5-HT) regulates a variety of visceral and physiological functions, including sleep. Polymorphisms in the 5-HT2A receptor gene can alter its transcription, affecting the number of receptors in the serotoninergic system, contributing to obstructive sleep apnea syndrome (OSAS). OBJECTIVE: The aim of this study was to determine the prevalence of the 102T-C and -1438G-A polymorphisms in the 5-HTR2A gene in Brazilian patients with and without OSAS. SUBJECTS AND METHODS: A cross-sectional study performed at the Otorhinolaryngology and Sleep Disorder Out Clinics, São José do Rio Preto Medical School, FAMERP. One hundred patients were examined as index cases and 100 persons as controls, of both genders to both groups. DNA was extracted from peripheral blood leukocytes, and the sites that encompassed both polymorphisms were amplified by PCR-RFLP. RESULTS: There was a significant prevalence of the male gender in index cases compared with the control group gender (p < 0.0001). There was no significant genotypic difference in the 102T-C polymorphism between the case and control groups (p = 1.000). The AA genotype of the -1438G-A polymorphism was more prevalent in the patients with OSAS compared with the controls (OR, 2.3; CI 95% 1.20-4.38; p = 0.01). CONCLUSIONS: There was no difference in the prevalence of the 102T-C polymorphism between patients with OSAS and the control group. Serotoninergic system dysfunction appeared to be related to OSAS. The -1438G-A polymorphism and OSAS are related in this studied Brazilian population.

Association of temporomandibular dysfunction with the 102T-C polymorphism in the serotonin receptor gene in Brazilian patients.

INTRODUCTION: Serotonin is a key neurotransmitter in the central nervous system. It has been suggested that serotoninergic dysfunction mediates the pathophysiology of temporomandibular dysfunction (TMD). Polymorphisms in the serotonin receptor gene (HTR2A) can alter its transcription, affecting the number of receptors in the serotoninergic system, altering nociceptive pain and hyperalgesia in TMD. The aim of this study is to investigate the association of the 102T-C polymorphism in the HTR2A gene in Brazilian patients with TMD. MATERIAL AND METHODS: This cross-sectional study examined 100 patients, of both genders, with TMD as index cases and 100 healthy volunteers as controls, also of both genders. DNA was extracted from peripheral blood leukocytes, and the site that encompassed the polymorphism in the HTR2A gene was amplified by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). RESULTS: Our results revealed that there were significantly more females among index cases compared with the control group (p < 0.05). The CC genotype of the 102T-C polymorphism was more frequent in patients with TMD vs. controls (OR: 2.25; 95% CI: 1.13-4.46; p < 0.05). CONCLUSIONS: The present study supports the view that the 102T-C polymorphism in the HTR2A gene is associated with TMD in this studied Brazilian population.

Polymorphisms in the 5-HTR2A gene related to obstructive sleep apnea syndrome.

UNLABELLED: Obstructive sleep apnea syndrome (OSAS) is one of the most complex disorders of sleep; it involves several genetic factors that contribute to the phenotype. Serotonin (5-HT) regulates a variety of visceral and physiological functions, including sleep. Gene 5-HTR2A polymorphisms may change the transcription of several receptors in the serotoninergic system, thereby contributing to OSAS. AIM: To investigate the prevalence of T102C and -1438G/A polymorphisms in the 5-HTR2A gene of patients with and without OSAS. MATERIAL AND METHOD: A molecular study of 100 index-cases and 100 controls of both genders. DNA was extracted from blood leukocytes samples and the regions that enclose both polymorphisms were amplified with PCR-RFLP. STUDY DESIGN: A cross-sectional case study. RESULTS: There was a significant prevalence of males in index cases compared to controls (p<0.0001). No significant genotypic differences between cases and controls were found in T102C polymorphisms (p=1.000).There were significant differences between the AA genotype of -1438G/A polymorphisms and patients with OSAS (OR:2.3; CI95%:1.20-4.38, p=0.01). CONCLUSION: Serotonergic mechanisms may be related to OSAS. There were no differences in the prevalence of T102C polymorphisms in patients with OSAS and the control group. There is evidence of an association between the -1438G /A polymorphism and OSAS.

Polymorphisms in the 5-HTR2A gene related to obstructive sleep apnea syndrome / Polimorfismos no gene HTR2A relacionados à síndrome da apneia obstrutiva do sono

Obstructive sleep apnea syndrome (OSAS) is one of the most complex disorders of sleep; it involves several genetic factors that contribute to the phenotype. Serotonin (5-HT) regulates a variety of visceral and physiological functions, including sleep. Gene 5-HTR2A polymorphisms may change the transcription of several receptors in the serotoninergic system, thereby contributing to OSAS. AIM: To investigate the prevalence of T102C and -1438G/A polymorphisms in the 5-HTR2A gene of patients with and without OSAS . MATERIAL AND METHOD: A molecular study of 100 index-cases and 100 controls of both genders. DNA was extracted from blood leukocytes samples and the regions that enclose both polymorphisms were amplified with PCR-RFLP. STUDY DESIGN: A cross-sectional case study. RESULTS: There was a significant prevalence of males in index cases compared to controls (p<0.0001). No significant genotypic differences between cases and controls were found in T102C polymorphisms (p=1.000).There were significant differences between the AA genotype of -1438G/A polymorphisms and patients with OSAS (OR:2.3; CI95 percent:1.20-4.38, p=0.01). CONCLUSION: Serotonergic mechanisms may be related to OSAS. There were no differences in the prevalence of T102C polymorphisms in patients with OSAS and the control group. There is evidence of an association between the -1438G /A polymorphism and OSAS.

A síndrome da apneia obstrutiva do sono (SAOS) é um dos distúrbios mais complexos do sono, envolvendo múltiplos fatores genéticos contribuintes para o fenótipo. A serotonina (5-HT) está envolvida na regulação de uma variedade de funções viscerais e fisiológicas, inclusive o sono. Polimorfismos no gene 5-HTR2A podem alterar a transcrição, afetando o número de receptores do sistema serotoninérgico, contribuindo para a SAOS. OBJETIVO: Investigar a prevalência dos polimorfismos T102C e -1438G/A no gene HTR2A em pacientes com e sem SAOS. MATERIAL E MÉTODO: Estudo molecular em 100 pacientes como casos-índice e em 100 como grupo controle, de ambos os gêneros. O DNA foi extraído de leucócitos de sangue periférico e realizada a amplificação das regiões que abrangem ambos os polimorfismos pelas técnicas da PCR-RFLP. DESENHO DO ESTUDO: Estudo de caso/controle em corte transversal. Resultados: Houve prevalência significativa do gênero masculino nos casos-índice em relação aos controles (p<0,0001). Para o polimorfismo T102C, não houve diferença genotípica significante entre casos e controles (p=1,000). Houve diferença significativa entre o genótipo AA do polimorfismo -1438G/A e pacientes com SAOS (OR:2,3; IC95 por cento:1,20-4,38; p=0,01). CONCLUSãO: Os mecanismos serotoninérgicos parecem estar relacionados a SAOS. Não há diferenças na prevalência do polimorfismo T102C entre os pacientes com SAOS e o grupo controle. Há evidências de associação entre o polimorfismo -1438G/A e a SAOS.

[Evaluation of testosterone serum levels in patients with obstructive sleep apnea syndrome]. / Avaliação dos níveis séricos de testosterona em pacientes com síndrome da apneia obstrutiva do sono.

UNLABELLED: Males with obstructive sleep apnea syndrome (OSAS) may present decreased testosterone serum levels because of hypoxemia. AIM: To correlate testosterone levels in OSAS patients with laboratory parameters. MATERIAL AND METHODS: 103 registries of OSAS patients were reviewed from 2002 to 2009. The following data collected: age when polysomnography was done, hematocrit and hemoglobin levels, total testosterone serum levels, BMI, apnea/hypopnea index (AHI), and O2 saturation. STUDY DESIGN: A cross-sectional retrospective case study. RESULTS: 79 patients (77%) had no hormonal changes, and 24 patients (23%) had decreased serum levels. In patients with normal testosterone levels, 70% were overweight; 63% with altered testosterone levels had obesity grade I (p<0.05). Patients with altered testosterone levels had significantly lower average doses of Ht, Hb and androgen compared to patients without altered androgen levels. The average BMI of patients with altered hormone levels was significantly higher compared to patients with normal hormone levels. CONCLUSIONS: The relationship between morning testosterone levels and obesity, and to a lesser degree age, AHI and hypoxemia may be the cause of central suppression of testosterone in these patients. Decreased blood HT and HB levels may be related to lower levels of circulating testosterone.

Avaliação dos níveis séricos de testosterona em pacientes com síndrome da apneia obstrutiva do sono / Evaluation of testosterone serum levels in patients with obstructive sleep apnea syndrome

Homens com síndrome da apneia obstrutiva do sono (SAOS) podem apresentar diminuição dos níveis de testosterona devido à hipóxia. OBJETIVOS: Relacionar os níveis séricos da testosterona, em pacientes com SAOS, com parâmetros clínico-laboratoriais. MATERIAL E MÉTODOS: Foram revisados 103 prontuários de pacientes com SAOS, entre os anos de 2002 e 2009, e coletados os seguintes dados: idade à época da realização da polissonografia, valores do Hematócrito e Hemoglobina, nível sérico da testosterona total, IMC, índice de apneia/hipopneia(IAH) e SatO2. FORMA DO ESTUDO: Estudo de casos retrospectivo em corte transversal. RESULTADOS: 79 pacientes (77 por cento) não apresentaram alteração hormonal e 24 (23 por cento) apresentaram níveis séricos inferiores. Dos pacientes com testosterona normal 70 por cento estavam com sobrepeso, enquanto que 63 por cento com testosterona alterada apresentaram obesidade grau I (p<0,05). Os pacientes com testosterona alterada apresentaram as dosagens médias do Ht e da Hb e dos níveis médios do andrógeno significantemente inferiores aos dos pacientes sem alteração androgênica. A média do IMC dos pacientes com alteração hormonal foi significativamente maior que a média daqueles sem alteração. CONCLUSÃO: A relação entre o perfil sérico da testosterona matinal e a obesidade e, em menor grau, a idade, o IAH e a hipóxia, podem ser responsáveis pela supressão central da testosterona nesses pacientes. A queda dos valores hematimétricos pode ser relacionada aos baixos níveis circulantes da testosterona.

Males with obstructive sleep apnea syndrome (OSAS) may present decreased testosterone serum levels because of hypoxemia. AIM: To correlate testosterone levels in OSAS patients with laboratory parameters. MATERIAL AND METHODS: 103 registries of OSAS patients were reviewed from 2002 to 2009. The following data collected: age when polysomnography was done, hematocrit and hemoglobin levels, total testosterone serum levels, BMI, apnea/hypopnea index (AHI), and O2 saturation. STUDY DESIGN: A cross-sectional retrospective case study. RESULTS: 79 patients (77 percent) had no hormonal changes, and 24 patients (23 percent) had decreased serum levels. In patients with normal testosterone levels, 70 percent were overweight; 63 percent with altered testosterone levels had obesity grade I (p<0.05). Patients with altered testosterone levels had significantly lower average doses of Ht, Hb and androgen compared to patients without altered androgen levels. The average BMI of patients with altered hormone levels was significantly higher compared to patients with normal hormone levels. CONCLUSIONS: The relationship between morning testosterone levels and obesity, and to a lesser degree age, AHI and hypoxemia may be the cause of central suppression of testosterone in these patients. Decreased blood HT and HB levels may be related to lower levels of circulating testosterone.

Six years of facial trauma care: an epidemiological analysis of 355 cases.

UNLABELLED: Facial traumas are frequent in emergencies, and they require the diagnosis of fractures and associated lesions. AIM: To analyze epidemiological data concerning facial trauma care. MATERIALS AND METHODS: Three hundred and fifty-five charts from patients with facial trauma treated by the Service of Otorhinolaryngology, from January 2002 to December 2008, were revised. The following data was collected: age, gender, etiology, anatomical localization of the fracture, associated injuries, alcohol consumption, treatment, and hospitalization. STUDY DESIGN: A retrospective historical longitudinal study. RESULTS: Most of the patients are young adult men (p<0.05) with a male:female ratio of 4:1(p<0.05). Interpersonal violence is the most prevalent cause of facial trauma (27.9%), followed by motor vehicle accidents (16.6%) (p<0.05). The mandible is the most prevalent facial bone fractured (44.2%), followed by nasal fracture (18.9%) (p<0.05). 41.1% of the patients consumed alcohol with a male:female ratio of 11.2:1 (p<0.05). Seventy-seven percent of the patients required surgical intervention (p<0.05) and 84.5% were hospitalized (p<0.05). CONCLUSION: Young male adults are the most prevalent victims of facial trauma, and interpersonal violence is responsible for the majority of the facial injuries. Most of the cases of facial trauma are associated with the consumption of alcohol. Further studies will be necessary to provide a clear understanding of the trends in the etiology of facial trauma.

Seis anos de atendimento em trauma facial: análise epidemiológica de 355 casos / Six years of facial trauma care: an epidemiological analysis of 355 cases

Traumas faciais são frequentes em emergências requerendo o diagnóstico de fraturas e lesões associadas. OBJETIVO: Avaliar dados epidemiológicos de atendimento em trauma facial. MATERIAL E MÉTODOS: Foram revisados 335 prontuários de pacientes com trauma facial tratados pelo Serviço de Otorrinolaringologia, no período de Janeiro de 2002 a Dezembro de 2008. Os seguintes dados foram coletados: idade, gênero, etiologia, local anatômico da fratura, lesão associada, consumo de álcool, tratamento e hospitalização. FORMA DO ESTUDO: Estudo de casos retrospectivo em corte longitudinal histórico. RESULTADOS: A maioria dos pacientes são homens adultos jovens (p<0,005) com uma proporção masculino:feminino de 4:1 (p<0,05). Violência interpessoal é a causa mais prevalente de trauma facial (27,9 por cento) seguida de acidente automobilístico (16,6 por cento) (p<0,05). Mandíbula é o osso facial fraturado mais prevalente (44,2 por cento) seguido pela fratura nasal (18,9 por cento) (p<0,05). Houve consumo de álcool em 41,1 por cento dos pacientes com uma proporção masculino:feminino de 11,2:1 (p<0,05). Setenta e sete por cento dos pacientes necessitaram de intervenção cirúrgica (p<0,05) e 84,5 por cento foram hospitalizados (p<0.05). CONCLUSÃO: Homens adultos jovens são as vítimas mais prevalentes em trauma facial e a violência interpessoal é a responsável pela maioria das lesões faciais. A maioria dos casos de traumatismo facial está associada ao consumo de álcool. Estudos posteriores serão sempre necessários a fim de permitir uma clara compreensão da tendência na etiologia do trauma facial.

Facial traumas are frequent in emergencies, and they require the diagnosis of fractures and associated lesions. AIM: To analyze epidemiological data concerning facial trauma care. MATERIALS AND METHODS: Three hundred and fifty-five charts from patients with facial trauma treated by the Service of Otorhinolaryngology, from January 2002 to December 2008, were revised. The following data was collected: age, gender, etiology, anatomical localization of the fracture, associated injuries, alcohol consumption, treatment, and hospitalization. STUDY DESIGN: A retrospective historical longitudinal study. RESULTS: Most of the patients are young adult men (p<0.05) with a male:female ratio of 4:1(p<0.05). Interpersonal violence is the most prevalent cause of facial trauma (27.9 percent), followed by motor vehicle accidents (16.6 percent) (p<0.05). The mandible is the most prevalent facial bone fractured (44.2 percent), followed by nasal fracture (18.9 percent) (p<0.05). 41.1 percent of the patients consumed alcohol with a male:female ratio of 11.2:1 (p<0.05). Seventy-seven percent of the patients required surgical intervention (p<0.05) and 84.5 percent were hospitalized (p<0.05). CONCLUSION: Young male adults are the most prevalent victims of facial trauma, and interpersonal violence is responsible for the majority of the facial injuries. Most of the cases of facial trauma are associated with the consumption of alcohol. Further studies will be necessary to provide a clear understanding of the trends in the etiology of facial trauma.