RESUMO
BACKGROUND: For patients with single sided deafness (SSD) or severe asymmetric sensorineural hearing loss (ASHL), cochlear implantation remains the only solution to restore bilateral hearing capacity. Prognostically, the duration of hearing loss in terms of audiological outcome is not yet clear. Therefore, the aim of this study was to retrospectively investigate the influence of subjective deafness duration on postoperative speech perception after cochlear implantation for SSD as well as its impact on quality of life. MATERIALS AND METHODS: The present study included a total of 36 adults aged 50.2 ± 15.5 years who underwent CI for SSD/ASHL at our clinic between 2010 and 2015. Patients were audiometrically assessed at 3 and 12-36 months postoperatively. Test results were correlated with self-reported duration of deafness. Quality of life was assessed by questionnaire. RESULTS: Mean duration of deafness was 193.9 ± 185.7 months. The side-separated hearing threshold showed an averaged target range between 30 and 40 dB HL. Freiburg monosyllable test increased from 0% pre-operatively to 20% after 3 months (p = 0.001) and to 50% after 12-36 months (p = 0.002). There was a significant correlation between audiometric outcome and subjective deafness duration at 12-36 months postoperatively (r = - 0.564; p = 0.02) with a cutoff for open-set monosyllable recognition at a duration of deafness of greater than 408 months. Quality of life was significantly improved by CI. CONCLUSIONS: CI implantation in unilaterally deafened patients provides objective and subjective benefits. Duration of deafness is unlikely to be an independent negative predictive factor and thus should not generally be considered as contraindication.
Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva Neurossensorial , Perda Auditiva Unilateral , Percepção da Fala , Adulto , Humanos , Perda Auditiva Unilateral/cirurgia , Inteligibilidade da Fala , Surdez/cirurgia , Surdez/reabilitação , Estudos Retrospectivos , Qualidade de Vida , Resultado do Tratamento , Audição , Perda Auditiva Neurossensorial/cirurgiaRESUMO
Overexpression of the vascular endothelial growth factor (VEGF) gene has been associated with advanced stage and poor survival in several cancers. The majority of disease-associated VEGF-single nucleotide polymorphisms (SNPs) locate within regulatory regions. Therefore, an influence of SNPs located in the promoter/5'-untranslated region (5'UTR) on transcription factor binding (TFB) and gene expression seems feasible. We reviewed the literature investigating a potential connection of VEGF-SNPs and transcriptional regulation of the VEGF gene. In addition, we employed transcription factor databases to search for VEGF-SNPs which have already been associated with diseases. The objective of this review is to gain an overview about an association of VEGF-SNPs and the transcription factor dependent regulation of the VEGF gene. A decreasing binding specificity of the transcription factor MZF1 in presence of the VEGF-SNP +405 C-allele has been reported. TF databases indicated a potential HIF binding site for the -2578 C-allele representing an important potential inducer of VEGF expression. Additionally, linkage disequilibrium of the -2578 A-allele and an 18 bp insertion increases the number of potential TFB sites. For the VEGF promoter SNP -1154 A/G an interaction with the HRE under participation of the SNP +405 C/G was supposed. The comprehension of the association of specific SNPs and TFB could be an essential part in our understanding of individual differences of VEGF regulation and course of diseases.
Assuntos
Regulação da Expressão Gênica , Transcrição Gênica , Fator A de Crescimento do Endotélio Vascular/genética , Regiões 5' não Traduzidas , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The aim of the study is to present the results of combination treatment for adult non-traumatic subglottic stenosis (SGS). This is a retrospective chart review of 12 female patients (age range 32-76 years) with idiopathic SGS (eight patients) and Wegener's granulomatosis. All patients had a hard and 11 a short (less than 1 cm) stenosis. Eleven patients were treated with endoscopic CO(2) laser, one with Nd-YAG laser. Topical triamcinolone was applied to all. In 10 patients, topical mitomycin C (MMC) was additionally applied. Symptom severity and airway resistance (AR) were evaluated pre- and post-interventionally. Postoperatively, oral steroids (and/or methotrexate) and proton pump inhibitors (PPI) were prescribed. Follow-up period ranged between 7 and 115 months. All patients reported a significant improvement in obstructive symptoms. Average AR preoperatively was 1.004 kPa/(L/s) and postoperatively 0.526 kPa/(L/s). Three patients underwent surgery once, 2 required a second surgery, 5 were operated 3 times, one 5 times, and one 7 times. The latter two patients had not received local MMC treatment. Endoscopic laser surgery combined with local MMC and triamcinolone application and postoperative oral steroid/methotrexate and PPI therapy provides a treatment option that results in prolongation of the symptom-free time intervals and avoidance of open surgery in patients with idiopathic and Wegener-associated hard and short SGS.
Assuntos
Anti-Inflamatórios/uso terapêutico , Granulomatose com Poliangiite/complicações , Laringoestenose/terapia , Terapia a Laser , Mitomicina/uso terapêutico , Inibidores da Síntese de Ácido Nucleico/uso terapêutico , Triancinolona/uso terapêutico , Administração Tópica , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Laringoscopia , Laringoestenose/etiologia , Lasers de Gás/uso terapêutico , Lasers de Estado Sólido/uso terapêutico , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The aim of this study is to determine differences in postoperative air-bone gap (ABG) after placement of teflon-platinum or nitinol middle ear prostheses in primary stapedotomy patients with otosclerosis. Thirty otosclerosis patients (24 female, 6 male; age 10-61 years) with primary stapedotomy were studied prospectively. Before and after surgery, the mean and standard deviations of the ABG were measured at eight frequencies (0.25-4 kHz). Patients were randomized into one of two groups receiving either teflon-platinum or nitinol prostheses. Hearing results were assessed 1 year after surgery. To assess the joint influence of treatment and frequency on ABG reduction, a linear mixed model was used (significance level was p = 5%). The Tukey-Kramer method was used to adjust for multiple comparisons. Significant differences were found between treatment groups (p < 0.0001) and between frequencies within the same treatment group (p < 0.0001) but no interaction (p = 0.7963), i.e. the reduction of the conductive components over frequencies was nearly parallel in both groups. Overall, patients in the Teflon group had a larger reduction of conductive components, on average 8.0 dB more reduction, than patients in the nitinol group. However, after adjusting for multiple comparisons, we could not identify a single frequency with a significant difference in reduction of conductive components. Use of the teflon-platinum prosthesis results in statistically non-significant better ABG closure at 0.25-4 kHz 1 year postoperatively than the use of the nitinol prosthesis.
Assuntos
Orelha Média/cirurgia , Prótese Ossicular , Otosclerose/cirurgia , Desenho de Prótese , Cirurgia do Estribo/instrumentação , Adolescente , Adulto , Ligas , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Platina , Politetrafluoretileno , Estudos ProspectivosRESUMO
Vestibular schwannomas (VS) are benign tumors of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). The NF2 gene is a tumor suppressor gene located on chromosome 22. Loss of the NF2 protein product, Merlin, is universal in both sporadic and NF2-related schwannomas and the loss or mutation of the gene is the only established causative event underlying schwannoma formation. Comparative genomic hybridization (CGH) was used to screen 20 sporadic VS to identify additional chromosomal regions that may harbor genes involved in VS-tumorigenesis. The most common change were losses on chromosome 22q. Additionally, losses were observed on chromosome 9p indicating a possible participation of the CDKN2A tumor suppressor gene in the genesis of VS. Gains were observed on 17q, 19p and 19q, which have been reported before in malignant peripheral nerve sheath tumors that are associated with neurofibromatosis type 1. Importantly, high level amplifications have been observed on 16p and 16q as well as on 9q, suggesting the possible involvement of several oncogenes in the tumorigenesis of VS. Our data suggest the involvement of various oncogenes and tumor suppressor genes might play a role in the genesis of the vestibular schwannomas apart from the inactivation of the NF2 gene.
Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 22/genética , Hibridização Genômica Comparativa/métodos , Citogenética/métodos , Neuroma Acústico/diagnóstico , Neuroma Acústico/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The retrosigmoid (suboccipital) approach is one of four surgical approaches for the treatment of vestibular schwannomas (acoustic neuromas). It is increasingly used by otologic surgeons, and in experienced hands is associated with improved results and more limited complications. Mortality rates are minimal and often zero, while postoperative sequelae, on the other hand, are not rare. In order to not only save the patient's life, but also to assure good quality of life after the surgery, one must consider many different aspects of management of the respective complications. In this review the issues of current management of CSF leak and meningitis, facial paresis, headache, hearing loss, unsteadiness, disequilibrium, vertigo, tinnitus, cerebellar and brain stem injuries or abscess, vascular complications and venous air embolism after retrosigmoid approach for removal of vestibular schwannomas are presented.
Assuntos
Neuroma Acústico/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Complicações Pós-Operatórias , Humanos , Procedimentos Cirúrgicos Otorrinolaringológicos/métodosRESUMO
Malignant triton tumour (MTT) is a rare, highly malignant neoplasm, characterized by a mixture of cells with nerve sheath and skeletal muscle differentiation. Cytogenetic analyses of this neoplasm are rare to date and none comparative genomic hybridisation (CGH) analysis has been published. In the present study we report about the genomic imbalances of a MMT analysed by CGH, in a 39-year-old male patient without neurofibromatosis. We observed the amplifications at chromosomal location 1p, 6p, 16p, 16q, 17p, 17q, 19p, 19q, 20p, and 22q. Comparing our results with those of previous studies, we found evidence for recurrent genomic aberrations at the chromosomes 1, 16, 17, 19, and 22 suggesting the involvement of several oncogenes in the genesis of MTT.
Assuntos
Aberrações Cromossômicas , Hibridização Genômica Comparativa/métodos , Neuroma Acústico/genética , Neuroma Acústico/patologia , Adulto , Biópsia por Agulha , Terapia Combinada , Análise Citogenética/métodos , Progressão da Doença , Evolução Fatal , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética/métodos , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neuroma Acústico/terapia , Procedimentos Neurocirúrgicos/métodos , Radioterapia Adjuvante , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Endocrine orbitopathy (EO) encompasses functional and cosmetic limitations. The aim of this study was to assess the health services situation of patients with EO treated at a multidisciplinary specialized center. METHODS: The medical records pertaining to the clinical spectrum, access route, and medical specialty of the referring physician of patients who were treated within a period of 5 years at a tertiary referral orbit center were systematically assessed. RESULTS: A total of 431 subjects with EO (female nâ¯=354, 82%; median age 40 years, range 5-79 years) were included in the study. Of the patients 148 (35%) and 123 (29%) were referred by family physicians and ophthalmologists, respectively. A sight-threatening optic nerve neuropathy was present in 11 (14.3%) men and 21 (5.9%) women (pâ¯=0.011). At least 2 other autoimmune diseases were found in 8 (10.4%) men and in 15 (4.3%) women (pâ¯=0.079). Psychotherapeutic support was utilized by 2 (2.6%) men and 92 (26%) women (pâ¯<0.001). An access route of 50â¯km or more was accepted by 14 (28%) men and 83 (43%) women (pâ¯=0.054). There was also an association between an access route ≥100â¯km and a prior medical treatment (odds ratio 3.78, 95% confidence interval 1.18-12.05, pâ¯=0.025). CONCLUSION: Men were more severely affected by EO than women and often had complex autoimmune diseases; however, male patients were less frequently willing to accept long access routes and barely used psychosocial support. Especially patients with further autoimmune diseases travelled long distances to be treated at a specialized center.
Assuntos
Oftalmopatia de Graves , Doenças do Nervo Óptico , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/epidemiologia , Oftalmopatia de Graves/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Óptico , Órbita , Encaminhamento e Consulta , Adulto JovemRESUMO
HYPOTHESIS: Expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) may have an impact on the growth characteristics of sporadic vestibular schwannomas (VSs). BACKGROUND: Vestibular schwannoma is a benign, slow-growing neoplasm that accounts for 6% of all intracranial tumors. The biological backgrounds for neoplastic growth and especially for the various growth patterns of VS remain largely unknown. Because several angiogenic and cytotrophic factors have been described to be involved in the growth of malignant tumors, we initiated this study to examine 2 major representatives of such growth factors in VS and their possible correlation to the growth characteristics of sporadic VSs. METHODS: Surgical specimens from 17 patients with sporadic VS were examined, and the expression of 2 major angiogenic and neurotrophic factors, bFGF and VEGF, was quantitatively analyzed at the mRNA and protein levels. The microvessel density (MVD) was defined by CD31 staining. RESULTS: All tumors showed expression of bFGF and VEGF at both the mRNA and protein levels. The mRNA expression and the protein expression of both growth factors correlated positive to tumor volume, to tumor growth index, and to MVD. CONCLUSION: The bFGF and VEGF mRNA expression and the bFGF and VEGF protein expression in sporadic VS correlates to the tumour volume, to the tumor growth index, and to the MVD. This might indicate an angiogenic and neurotrophic influence of these factors and a possible involvement in the growth of sporadic VS.
Assuntos
Neoplasias da Orelha/metabolismo , Neoplasias da Orelha/patologia , Fator 2 de Crescimento de Fibroblastos/biossíntese , Neuroma Acústico/metabolismo , Neuroma Acústico/patologia , Fator A de Crescimento do Endotélio Vascular/biossíntese , Adulto , Idoso , Capilares/patologia , Progressão da Doença , Neoplasias da Orelha/irrigação sanguínea , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Neuroma Acústico/irrigação sanguínea , Molécula-1 de Adesão Celular Endotelial a Plaquetas/biossíntese , Molécula-1 de Adesão Celular Endotelial a Plaquetas/genética , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Fluxo Sanguíneo Regional/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
In the present article we report a cholesteatoma of the hypotympanum extending to the jugular foramen in a 16-year-old male with Treacher Collins syndrome. Preoperative imaging excluded jugular paraganglioma and set the diagnosis of cholesteatoma. We discuss the operative treatment via a large hypotympanotomy and creation of an open hypotympanic cavity. To the authors' knowledge this is the first description of hypotympanal cholesteatoma with such an extension, being treated through this approach.
Assuntos
Colesteatoma da Orelha Média/cirurgia , Orelha Média/cirurgia , Disostose Mandibulofacial/diagnóstico por imagem , Adolescente , Colesteatoma da Orelha Média/complicações , Colesteatoma da Orelha Média/diagnóstico , Orelha Média/diagnóstico por imagem , Orelha Média/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Disostose Mandibulofacial/complicações , Disostose Mandibulofacial/patologia , Tomografia Computadorizada por Raios XRESUMO
CONTEXT: Mutations in the four subunits of succinate dehydrogenase (SDH) are the cause for the hereditary paraganglioma (PGL) syndrome types 1-4 and are associated with multiple and recurrent pheochromocytomas and PGLs. SDHC mutations most frequently result in benign, nonfunctional head-and neck PGLs (HNPGLs). The malignant potential of SDHC mutations remains unclear to date. OBJECTIVES: We report a patient with malignant PGL carrying a SDHC mutation and compare her case with two others of the same genotype but presenting with classic benign HNPGLs. Loss of heterozygosity (LOH) was demonstrated in the malignant PGL tissue. DESIGN: In three unrelated patients referred for routine genetic testing, SDHB, SDHC, and SDHD genes were sequenced, and gross deletions were excluded by multiplex ligation-dependent probe amplification (MLPA). LOH was determined by pyrosequencing-based allele quantification and SDHB immunohistochemistry. RESULTS: In a patient with a nonfunctioning thoracic PGL metastatic to the bone, the lungs, and mediastinal lymph nodes, we detected the SDHC mutation c.397C>T predicting a truncated protein due to a premature stop codon (p.Arg133*). We demonstrated LOH and loss of SDHB protein expression in the malignant tumor tissue. The two other patients also carried c.397C>T, p.Arg133*; they differed from each other with respect to their tumor characteristics, but both showed benign HNPGLs. CONCLUSIONS: We describe the first case of a malignant PGL with distant metastases caused by a SDHC germline mutation. The present case shows that SDHC germline mutations can have highly variable phenotypes and may cause malignant PGL, although malignancy is probably rare.
Assuntos
Mutação em Linhagem Germinativa , Proteínas de Membrana/genética , Paraganglioma/genética , Neoplasias da Coluna Vertebral/genética , Arginina/genética , Feminino , Heterogeneidade Genética , Predisposição Genética para Doença , Tumor do Glomo Jugular/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Cardíacas/genética , Neoplasias Cardíacas/secundário , Humanos , Perda de Heterozigosidade , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Paraganglioma/patologia , Fenótipo , Fatores de Risco , Neoplasias da Coluna Vertebral/patologiaRESUMO
Aberrant inactivation of tumor suppressor genes by promoter hypermethylation has been recognized as a crucial step of tumor development and is related to aggressiveness and therapy resistance. To identify potential novel treatment strategies, we evaluated pharmacological genome demethylation for the increase of irradiation treatment effectiveness in head and neck squamous cell carcinoma (HNSCC) in this in vitro study. HNSCC cells were cultured with 2 different concentrations of 5-azacytidine (5-Aza) for 72 h, followed by a single fraction irradiation with 4 or 50 Gy, respectively. To show successful genome demethylation, the methylation status of the tumor suppressor gene hic1 (hypermethylated in cancer) promoter was analyzed by methylation specific PCR (MSP) as well as hic1 transcription by quantitative RT-PCR. Survival, apoptosis, viability, and migration of the tumor cells were analyzed as functional parameters of combined treatment response. After 5-Aza treatment the hic1 promoter was demethylated and gene transcription restored demonstrating genome demethylation. 5-Aza treated cells tended to be less viable and showed decreased survival indicated by lower colony numbers. Apoptosis and migration were not affected. The combined application of irradiation and 5-Aza significantly reduced survival compared to the single treatments. Accordingly, apoptosis was strongly increased after combined 4 Gy/5-Aza treatment. Viability was not additionally affected by combined treatment. Migration was affected weakly by combined high dosage irradiation/5Aza treatment. Our data show that the combined application of 5-Aza and irradiation is effective in vitro. A demethylating concept prior to irradiation should be further evaluated for its potential to reduce irradiation resistance.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Azacitidina/farmacologia , Carcinoma de Células Escamosas/genética , Metilação de DNA/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/genética , Tolerância a Radiação/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Regiões Promotoras Genéticas/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Ativação Transcricional/efeitos dos fármacosRESUMO
Promoter hypermethylation of tumor suppressor genes (TSGs) is a common feature of primary cancer cells. However, to date the somatic epigenetic events that occur in head and neck squamous cell carcinoma (HNSCC) tumorigenesis have not been well-defined. In the present study, we analyzed the promoter methylation status of the genes mutL homolog 1 (MLH1), Ras-association domain family member 1 (RASSF1A) and O-6-methylguanine-DNA methyltransferase (MGMT) in 23 HNSCC samples, three control tissues and one HNSCC cell line (UM-SCC 33) using methylation-specific PCR (MSP). The expression of the three proteins was quantified by semi-quantitative immunohistochemical analysis. The cell line was treated with the demethylating agent 5-azacytidine (5-Aza) and the methylation status after 5-Aza treatment was analyzed by MSP and DNA sequencing. Proliferation was determined by Alamar blue staining. We found that the MGMT promoter in 57% of the analyzed primary tumor samples and in the cell line was hypermethylated. The MLH promoter was found to be methylated in one out of 23 (4%) tumor samples while in the examined cell line the MLH promoter was unmethylated. The RASSF1A promoter showed methylation in 13% of the tumor samples and in the cell line. MGMT expression in the group of tumor samples with a hypermethylated promoter was statistically significantly lower compared to the group of tumors with no measured hypermethylation of the MGMT promoter. After treatment of the cell line with the demethylating agent 5-Aza no demethylation of the methylated MGMT and RASSF1A genes were determined by MSP. DNA sequencing verified the MSP results, however, increased numbers of unmethylated CpG islands in the promoter region of MGMT and RASSF1A were observed. Proliferation was significantly (p<0.05) reduced after treatment with 5-Aza. In summary, we have shown promoter hypermethylation of the tumor suppressor genes MGMT and RASSF1A in HNSCC, suggesting that this epigenetic inactivation of TSGs may play a role in the development of HNSCC. 5-Aza application resulted in partial demethylation of the MGMT and RASSF1A TSGs and reduced proliferation of the tumor cells suggesting further evaluation of 5-Aza for HNSCC treatment.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Azacitidina/farmacologia , Carcinoma de Células Escamosas/genética , Proliferação de Células/efeitos dos fármacos , Metilação de DNA/efeitos dos fármacos , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Inibidores Enzimáticos/farmacologia , Genes Supressores de Tumor , Neoplasias de Cabeça e Pescoço/genética , Proteínas Nucleares/genética , Regiões Promotoras Genéticas/efeitos dos fármacos , Proteínas Supressoras de Tumor/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Ilhas de CpG , Metilases de Modificação do DNA/antagonistas & inibidores , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/antagonistas & inibidores , Enzimas Reparadoras do DNA/metabolismo , Remoção de Radical Alquila , Relação Dose-Resposta a Droga , Regulação para Baixo , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteína 1 Homóloga a MutL , Proteínas Nucleares/metabolismo , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/metabolismoRESUMO
OBJECTIVES/HYPOTHESIS: Chronic rhinosinusitis (CRS) is a multifactorial disease that probably arises as a result of genetic diversity and environmental factors. SPINK5 is a serine protease inhibitor, which is supposed to be an important regulator of epithelial barrier maintenance. The role of SPINK5 polymorphisms and expression in CRS, especially in individuals with aspirin intolerance, is unclear. STUDY DESIGN: SPINK5 single-nucleotide polymorphisms (SNPs) and SPINK5 expression levels were correlated with CRS without (CRSsNP) and with nasal polyps (CRSwNP), aspirin intolerance, asthma, and allergies. METHODS: One hundred four nasal tissue samples, 15 from patients with CRSsNP, 59 from patients with CRSwNP, and 30 from healthy controls of the inferior turbinate, were analyzed for their SPINK5 status. Genotypes of four SPINK5 single nucleotide polymorphism (SNPs; G1258A, G2475T, A2915G, and A1103G), as well as SPINK5 mRNA expression levels, were determined by polymerase chain reaction. RESULTS: No correlation between any SPINK5 SNP and CRSsNP, CRSwNP, or allergies and asthma was observed. The heterozygous SNPs G1258A and A1103G were observed more frequently in aspirin-intolerant patients; the homozygous (A/A) genotype of SNP 1258 and the homozygous (G/G) genotype SNP 1103 were less frequent. There was no correlation between the analyzed SNPs and the level of SPINK5 expression. It was noted that in individuals with CRSwNP, aspirin intolerance, and allergies, SPINK5 expression was lowered. CONCLUSIONS: G1258A and A1103G polymorphisms are distinctive for the aspirin intolerance syndrome. Lowered SPINK5 expression might be a contributing factor leading to CRS, and appears to be characteristic for patients suffering from aspirin intolerance and from allergies.
Assuntos
Regulação da Expressão Gênica , Polimorfismo de Nucleotídeo Único , Proteínas Secretadas Inibidoras de Proteinases/genética , Rinite/genética , Sinusite/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina , Asma/genética , Asma/patologia , Doença Crônica , Hipersensibilidade a Drogas , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Pólipos Nasais/genética , Pólipos Nasais/patologia , Reação em Cadeia da Polimerase/métodos , Proteínas Secretadas Inibidoras de Proteinases/metabolismo , RNA Mensageiro/análise , Valores de Referência , Rinite/metabolismo , Estudos de Amostragem , Sensibilidade e Especificidade , Inibidor de Serinopeptidase do Tipo Kazal 5 , Sinusite/metabolismo , Técnicas de Cultura de Tecidos , Adulto JovemRESUMO
Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), ultrasound and near-infrared spectrometry were used to evaluate tumor vessel integrity. Finally, tumors were explanted and VEGF, basic fibroblast growth factor (bFGF), vessel density, proliferation and apoptotic activity were analyzed by immunohistochemistry. Irradiation caused VEGF release and we found evidence for VEGF-mediated vessel protection. In the tumors derived from the combined treatment, blood volume was decreased, and apoptotic indices were increased. Remarkably, bFGF levels and proliferative indices were also increased. Combined irradiation/anti-VEGF treatment resulted in the desired VEGF depletion and increased tumor cell apoptosis. Nonetheless, bFGF and proliferation also increased, possibly suggesting a compensatory response. The application of additional targeted drugs may help develop more effective SCC treatments.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Animais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Linhagem Celular Tumoral , Hemodinâmica , Humanos , Camundongos , Camundongos Nus , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Arachnoid cysts are benign intracranial lesions that are typically diagnosed incidentally. They are divided into two types: congenital and acquired. Acquired arachnoid cysts are rare and usually arise after trauma, infection, or haemorrhage. In this report, a rare case of an iatrogenic multiloculated arachnoid cyst as an unusual complication of a skull base defect is presented. It extended extracranially into the sphenoid sinus, the ethmoid, the infratemporal fossa, the nasopharynx and the nasal cavity, as well as into the pterygomaxillary and retromaxillary space, appearing with a distinct clinical picture. We discuss the differential diagnosis and the potential causes of the lesion and provide a brief review of the literature.
Assuntos
Angiofibroma/cirurgia , Cistos Aracnóideos/etiologia , Craniotomia/efeitos adversos , Neoplasias Nasofaríngeas/cirurgia , Complicações Pós-Operatórias/etiologia , Base do Crânio/patologia , Adulto , Cistos Aracnóideos/diagnóstico por imagem , Cistos Aracnóideos/cirurgia , Fossa Craniana Média , Dura-Máter/patologia , Dura-Máter/cirurgia , Humanos , Doença Iatrogênica , Imageamento por Ressonância Magnética , Masculino , Mucocele/cirurgia , Cavidade Nasal/diagnóstico por imagem , Nasofaringe/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/cirurgia , Radiografia , Base do Crânio/cirurgia , Seio Esfenoidal/diagnóstico por imagemRESUMO
ABSTRACT Carotid blowout is a devastating complication in patients with head and neck malignancy. The traditional surgical treatment for carotid blowout is often technically difficult and is associated with an unacceptably high morbidity and mortality. Recently, endovascular therapy has been proposed for head and neck surgical patients. Preliminary reports showed a better outcome with less morbidity and mortality compared to the previous treatment modalities. The use of such techniques in cases of impending or acute carotid blowout syndrome has been previously described to be beneficial for palliative head and neck cancer patients as well. We introduce a case of a head and neck cancer patient receiving palliative care, presenting with threatened carotid blowout, who was managed with endovascular placement of a covered stent under elective conditions in order to prevent an inevitable carotid rupture. In the present case endovascular carotid stenting allowed preservation of the vessel, prevented the dramatic situation of carotid rupture, and facilitated a rapid hospital discharge without any neurologic or stenting sequelae.