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1.
J Pers Med ; 13(9)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37763059

RESUMO

OBJECTIVE: Odontogenic sinusitis (OS) is a well-known and important border of specialties in otorhinolaryngology and dentoalveolar surgery. Odontogenic sinusitis can develop due to iatrogenic harm or odontogenic infection. The gold standard diagnostic method is clinical and radiological-CBCT (cone beam computed tomography)-examination. The treatment of this condition requires collaboration between ENT and dentoalveolar surgery specialists and can be non-surgical or surgical based on staging. This paper aims to share the results of our clinical study whereby complex therapy was administered by a dentoalveolar surgeon and an otorhinolaryngologist in cooperation. PATIENTS AND METHODS: We conducted a retrospective study comprising 111 OS patients who underwent complex therapy between 2016 and 2023 at Semmelweis University, Budapest, Hungary. All patients were treated with concurrent FESS (functional endoscopic sinus surgery) and dentoalveolar surgery. Follow-up was based on symptoms, clinical examination and CBCT imaging. RESULTS: Of the 111 patients, 107 were successfully treated with concurrent FESS and dentoalveolar surgery, and only 4 had further symptoms following the complex therapy and needed retreatment. CONCLUSIONS: The complex, single-session therapy involving FESS and oral surgery is an effective treatment method, which is less invasive and associated with fewer complications compared to previous interventions, such as the Luc-Caldwell procedure.

2.
Orv Hetil ; 164(19): 729-738, 2023 May 14.
Artigo em Húngaro | MEDLINE | ID: mdl-37182197

RESUMO

INTRODUCTION: Postmeningitis deafness appears in 0-11% of the meningitis cases. Cochlear ossification can develop in these patients, which may make the hearing rehabilitation impossible with cochlear implantation. Due to ossification, it is critical to refer patients to the implant centre without any delay. OBJECTIVE: The aim of this study was to examine the time factor between the appearance of deafness and the first examination in a cochlear implant centre, the possibilities and effectivity of hearing rehabilitation. METHOD: In our tertial referral centre, postmeningitis deafened patients were examined between 2014 and 2022 retrospectively. Hearing results, imaging, possibilities of rehabilitation, complications of cochlear implantations and the hearing results were investigated. RESULTS: 8 patients (3 children, 5 adults) were investigated. The time between the start of deafness and the first appearance varied between 3 weeks to 9 years. Bilateral profound hearing loss was measured in all patients. In 6 cases, cochlear ossification was observed (4 patients bilateral). Cochlear implantation was conducted in 5 patients (4 bilateral, 1 unilateral). In 3 cases, implantation was impossible due to severe ossification. Hearing results showed good hearing levels with poor speech perception in all cases. DISCUSSION: The rehabilitation of severe hearing loss caused by meningitis can present many challenges to clinicians. A critical point in the care is the urgent referral of patients to a cochlear implantation centre as soon as possible after the life-threatening condition has passed. The implementation of further diagnostic and the earliest possible implantation is the responsibility of the implantation centre itself. CONCLUSION: It is recommended to develop a new protocol with the involvement of allied professions to clear patient pathways for an effective treatment strategy. Orv Hetil. 2023; 164(19): 729-738.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva , Meningite , Criança , Adulto , Humanos , Estudos Retrospectivos , Fatores de Tempo , Audição , Implante Coclear/métodos , Perda Auditiva/etiologia , Perda Auditiva/cirurgia , Meningite/complicações , Resultado do Tratamento , Surdez/etiologia , Surdez/cirurgia
3.
Orv Hetil ; 161(18): 756-760, 2020 05 01.
Artigo em Húngaro | MEDLINE | ID: mdl-32338489

RESUMO

Despite the significant improvement in surgical and intensive care therapy, esophageal perforation is still a severe, life-threatening condition. As the underlying causes, the accompanying disorders, the localization and the extent of the inflammation vary, the surgeon may sometimes encounter unexpected situations. A 58-year-old female developed necrotizing mediastinitis due to esophageal perforation as the result of incarcerated thoracic hernia of the stomach, therefore, we had to perform esophagus extirpation and cervical esophagostomy. During the reconstruction of the intestinal tract, we found shrinkage of the complete esophageal stump with unknown cause. The gastric sleeve was joined to the hypopharynx. Insufficiency was solved with conservative therapy. The patient regained partial swallowing ability after complex dysphagia treatment. Hyophapharyngo-gastrostomy done due to non-malignant disease is extremely rare in the literature, however, it can be a surgical technique of choice if required as in our case. It should be followed by rehabilitation done by a team, with emphasis on dysphagia treatment. Orv Hetil. 2020; 161(18): 756-760.


Assuntos
Perfuração Esofágica/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Esofagectomia , Feminino , Gastrostomia , Humanos , Hipofaringe/cirurgia , Pessoa de Meia-Idade
4.
Eur Arch Otorhinolaryngol ; 276(6): 1643-1647, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30949825

RESUMO

INTRODUCTION: As average life-expectancy increases, a sufficient hearing rehabilitation for elderly patients with severe-to-profound sensorineural hearing loss becomes more important. Cochlear implantation is a relatively safe surgical procedure also for elderly patients, the higher risk is caused by general anesthesia. We report on four patients who underwent cochlear implantation under local anesthesia. METHODS: After detailed preoperative examinations (audiological tests, imaging, genetic tests, evaluation of motivation and compliance of the patient), four patient with severe-to-profound hearing loss were selected for cochlear implantation under local anesthesia. For the electrode insertion, we used the posterior suprameatal approach technique. Pre- and postoperative pure tone audiometry and speech-perception tests were conducted to prove the success of the procedure. RESULTS: The mentioned technique was applied; the average length of the operation was 52 min. The intraoperative measurements showed normal impedance and normal neuronal response telemetry, all the patients had sound experience during the intraoperative examination of the engineer. No complications were observed. The postoperative audiological tests showed a significant increase in the hearing perception. CONCLUSION: Cochlear implantation under local anesthesia is a safe and fast procedure for elderly patients. The intraoperative sound experience can give an extra motivation in the postoperative rehabilitation. Our results prove that by carefully selected elderly patients cochlear implantation can assure a significant increase in speech perception. We can establish that the new posterior suprameatal approach technique combined with local anesthesia presents a viable future option for those patients who were inoperable beforehand because of high risks of general anesthesia.


Assuntos
Anestesia Local/métodos , Implante Coclear/métodos , Perda Auditiva Neurossensorial , Idoso , Audiometria de Tons Puros/métodos , Feminino , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/psicologia , Perda Auditiva Neurossensorial/cirurgia , Humanos , Masculino , Seleção de Pacientes , Percepção da Fala , Resultado do Tratamento
5.
Ear Nose Throat J ; 97(7): E4-E7, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30036438

RESUMO

When cochlear implantation was first introduced, the mastoidectomy and posterior tympanotomy approach was the most frequently used technique to gain access to the middle ear and the cochlea. Since 2000, several authors have routinely used a non-mastoidectomy nonposterior tympanotomy technique, which has undergone several modifications. Alternative surgical techniques for cochlear implantation have recently been introduced, such as endomeatal-alone or suprameatal-alone and combined posterior tympanotomy/endomeatal approaches. The goal of this study was to describe another modification of this less invasive technique to perform cochlear implantation. Cochlear implantations were performed between January 1, 2002, and December 31, 2012, in 220 patients through the posterior suprameatal approach. In reviewing our experiences, we have concluded that this approach, which eliminates the need for mastoidectomy, is considered safe, time-efficient, and minimally invasive. The possible pitfalls and the microsurgical relevance of anatomic structures of this technique are discussed in detail. Using this technique, not all classical anatomic orientation points are identified. However, certain landmarks predict the depth and the three-dimensional location of invisible anatomic structures.


Assuntos
Pontos de Referência Anatômicos/cirurgia , Cóclea/cirurgia , Implante Coclear/métodos , Orelha Média/cirurgia , Processo Mastoide/cirurgia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Cóclea/anatomia & histologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
6.
Int J Artif Organs ; 40(6): 307-312, 2017 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-28525668

RESUMO

INTRODUCTION: The aim of this study was to compare the paranasal sinus volumes obtained by manual and semiautomatic imaging software programs using both CT and CBCT imaging. METHODS: 121 computed tomography (CT) and 119 cone beam computed tomography (CBCT) examinations were selected from the databases of the authors' institutes. The Digital Imaging and Communications in Medicine (DICOM) images were imported into 3-dimensonal imaging software, in which hand mode and semiautomatic tracing methods were used to measure the volumes of both maxillary sinuses and the sphenoid sinus. The determined volumetric means were compared to previously published averages. RESULTS: Isometric CBCT-based volume determination results were closer to the real volume conditions, whereas the non-isometric CT-based volume measurements defined coherently lower volumes. By comparing the 2 volume measurement modes, the values gained from hand mode were closer to the literature data. Furthermore, CBCT-based image measurement results corresponded to the known averages. CONCLUSIONS: Our results suggest that CBCT images provide reliable volumetric information that can be depended on for artificial organ construction, and which may aid the guidance of the operator prior to or during the intervention.


Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Processamento de Imagem Assistida por Computador/métodos , Prótese Maxilofacial , Seios Paranasais , Órgãos Artificiais/normas , Humanos , Tamanho do Órgão , Seios Paranasais/diagnóstico por imagem , Seios Paranasais/patologia , Seios Paranasais/cirurgia
7.
Pathol Oncol Res ; 21(3): 643-50, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25547827

RESUMO

Head and neck squamous cell carcinomas (HNSCC) show diverse clinicopathological features and are mostly linked with poor outcome. In this study, we tested if the expression of tumor growth, cell cycle and basement membrane anchorage related biomarkers allow prognostic and clinicopathological stratification of HNSCC. Archived HNSCC samples from 226 patients included into tissue microarrays (TMA) were tested using immunohistochemistry. Histopathological evaluation and the analysis of immunostaining for EGFR, Ki67, p53, p16(ink4) and Collagen XVII proteins were carried out in digital whole slides. Statistical evaluation was carried out using Pearson's Chi-square test and Kaplan-Meier survival analysis. In the tested cohort, hypopharyngeal cancers had the least favorable, and glottic cancers had the most favorable prognosis. High Ki67 positive tumor cell fractions were associated with significantly worse prognosis and elevated rate of lymph node metastasis. Both Ki67 and EGFR expression correlated significantly with the tumor localization. Ki67 index was the highest in the hypopharyngeal region and it proved to be the lowest in the glottic region. EGFR expression was the highest in the oral cavity and the lowest in the glottic region. The survival rate of patients with p16(ink4)-negative cancer was significantly lower than of those with p16(ink4)-positive disease. A significant inverse correlation was found between histological grade and the prognosis of HNSCC. Our data support that elevated Ki67 positive proliferating cell fractions contribute to the unfavorable prognosis of hypopharyngeal cancers, while glottic cancers have the most favorable prognosis because of the lowest Ki67 expression rate.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoantígenos/metabolismo , Carcinoma de Células Escamosas/mortalidade , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Receptores ErbB/metabolismo , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Técnicas Imunoenzimáticas , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Colágenos não Fibrilares/metabolismo , Prognóstico , Taxa de Sobrevida , Análise Serial de Tecidos , Proteína Supressora de Tumor p53/metabolismo , Colágeno Tipo XVII
8.
Pathol Oncol Res ; 17(3): 779-84, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21660524

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is an aggressive neoplastic disease of the lymphatic system, the activated B-cell type of this disease is likely to have a substantially worse prognosis. In this study, we report the favorable outcome of the activated B-cell type of DLBCL, though untreated, 7 years after diagnosis. In 2003, DLBCL localized to the root of tongue was found in the patient complaining of dysphonia and a pharyngeal globus perception but the patient did not agree to get any active hematological treatment. During the following years, the patient did not have any complaints. At the otorhinolaryngological control examination, in 2010, she was complaint-free, had normal laboratory parameters. Moreover a PET-CT scan did not reveal metabolic activity relating to malignancy. The extraordinary disease process can be explained by the spontaneous regression of the activated B-cell type DLBCL. Spontaneous regression of oral lymphoma has been published only exceptionally. To our knowledge, no report of spontaneous regression of activated B-cell type DLBLC has been reported.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico , Regressão Neoplásica Espontânea , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Remissão Espontânea , Tomografia Computadorizada por Raios X
9.
Lancet Oncol ; 12(4): 333-43, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21377930

RESUMO

BACKGROUND: No treatments are presently available to increase survival in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy. We aimed to assess efficacy and safety of zalutumumab, a human IgG1 monoclonal antibody targeting the epidermal growth factor receptor, for overall survival in such patients. METHODS: In our open-label, parallel-group, phase 3, randomised trial, we randomly allocated patients with squamous-cell carcinoma of the head and neck who were regarded as incurable with standard therapy, a WHO performance status of 0-2, and progressive disease within 6 months of platinum-based therapy in a 2:1 ratio to receive zalutumumab plus best supportive care (zalutumumab group) or best supportive care with optional methotrexate (control group) at medical centres in Europe, Brazil, and Canada. Randomisation was done via a centralised interactive voice-response system, stratified by performance status. Data were analysed when the randomisation code was broken, after the completion of the accrual and cleaning of the relevant data. An independent review committee, masked to treatment assignment, assessed tumour response and disease progression according to response evaluation criteria in solid tumours. Zalutumumab was given weekly by individual dose titration on the basis of skin rash. After a prespecified 231 deaths, we included all randomised patients in the survival analyses and all patients receiving at least one session of therapy in the safety analysis. The primary endpoint was overall survival, although progression-free survival was also assessed. This trial is registered with ClinicalTrials.gov, NCT00382031. FINDINGS: We randomly allocated 191 (67%) of 286 eligible patients to the zalutumumab group and 95 (33%) to the control group. Median overall survival was 6.7 months (95% CI 5.8-7.0) in the zalutumumab group and 5.2 months (4.1-6.4) in the control group (hazard ratio [HR] for death, stratified by WHO performance status, was 0.77, 97.06% CI 0.57-1.05; unadjusted p=0.0648). Progression-free survival was longer in the zalutumumab group than in the control group (HR for progression or death, stratified by WHO performance status, was 0.63, 95% CI 0.47-0.84; p=0.0012). 189 patients given zalutumumab and 94 controls were included in the safety analysis. The most common grade 3-4 adverse events were rash (39 [21%] patients in the zalutumumab group vs none in the control group), anaemia (11 [6%] vs five [5%]), and pneumonia (nine [5%] vs two [2%]). 28 (15%) patients in the zalutumumab group had grade 3/4 infections compared with eight (9%) in the control group. The most common serious adverse events were tumour haemorrhage (28 [15%] patients given zalutumumab vs 13 [14%] controls), pneumonia (13 [7%] vs three [3%]), and dysphagia (11 [6%] vs two [2%]). INTERPRETATION: Although zalutumumab did not increase overall survival, progression-free survival was extended in patients with recurrent squamous-cell carcinoma of the head and neck who had failed platinum-based chemotherapy. Zalutumumab dose titration on the basis of rash is safe. FUNDING: Genmab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Carcinoma/tratamento farmacológico , Carcinoma/mortalidade , Carcinoma de Células Escamosas , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/mortalidade , Neoplasias de Células Escamosas/tratamento farmacológico , Neoplasias de Células Escamosas/mortalidade , Compostos Organoplatínicos/uso terapêutico , Terapia de Salvação , Carcinoma de Células Escamosas de Cabeça e Pescoço , Falha de Tratamento
10.
Clin Ther ; 29(1): 84-98, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17379049

RESUMO

BACKGROUND: Most cases of vertigo are attributable to both peripheral and central vestibular disorders. Therefore, it would be of interest to determine whether a combination therapy having both peripheral and central actions would translate into more efficient symptom relief. OBJECTIVE: This study was conducted to evaluate the efficacy and tolerability of a fixed low-dose combination of cinnarizine 20 mg + dimenhydrinate 40 mg in the treatment of vertigo of central, peripheral, or combined central/peripheral origin. METHODS: This was a prospective, multicenter, randomized, double-blind, active- and placebo-controlled, parallel-group, outpatient study in men and women (age >30 years) with central, peripheral, or combined central/peripheral vestibular vertigo. Patients who assessed > or =1 vertigo symptom as being of medium intensity (> or =2) on a 5-point visual analog scale (from 0 = no symptoms to 4 = very severe symptoms) and who had abnormal vestibulospinal movement patterns on cramocorpography were eligible. Patients were randomly assigned to receive 1 tablet of the fixed combination of cinnarizine 20 mg + dimenhydrinate 40 mg, cinnarizine 50 mg, dimenhydrinate 100 mg, or placebo 3 times daily for 4 weeks. The primary efficacy end point was the decrease in mean vertigo score (MVS), which was composed of 12 individual vertigo symptoms, each assessed on the 5-point visual analog scale after 4 weeks of treatment. RESULTS: The study enrolled 246 patients, of whom 239 were evaluable for efficacy. Approximately two thirds of the efficacy population were female and one third male. The mean age was 51.3 years, and the mean duration of vertigo was 2.6 years. The least squares mean (SD) change from baseline in MVS was significantly greater in the group receiving the fixed combination (1.37 [0.66]) than in any of the comparator groups (cinnarizine 50 mg: 0.87 [0.53]; dimenhydrinate 100 mg: 0.83 [0.66]; placebo: 0.76 [0.48]; all comparisons, P < 0.001). The differences were clinically relevant, based on the Mann-Whitney estimator. The incidence of vertigo-associated nausea was significantly reduced in the fixed-combination group relative to the comparator groups (P< or = 0.016). Thirty-four patients reported adverse events, 6 each in the fixed combination and placebo groups, 12 in the cinnarizine group, and 10 in the dimenhydrinate group. None of these adverse events were considered serious. After 4 weeks of treatment, the tolerability of treatment was rated as very good or good by 57 (96.6%) patients in the fixed-combination group; the values for cinnarizine, dimenhydrinate, and placebo were 54 (93.1%), 42 (72.4%), and 50 (87.7%), respectively. CONCLUSIONS: In this study, the fixed low-dose combination of cinnarizine 20 mg + dimenhydrinate 40 mg was effective, clinically beneficial, and well tolerated in patients with vestibular vertigo of central and/or peripheral origin. It was significantly more effective in reducing the MVS compared with placebo and the routinely prescribed higher doses of cinnarizine (50 mg) and dimenhydrinate (100 mg).


Assuntos
Cinarizina/uso terapêutico , Dimenidrinato/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Vertigem/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cinarizina/efeitos adversos , Dimenidrinato/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Antagonistas dos Receptores Histamínicos H1/efeitos adversos , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico
11.
Cytometry A ; 67(2): 151-60, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16163698

RESUMO

BACKGROUND: The prognostic divergence of laryngeal and hypopharyngeal carcinomas is well known. Hypopharyngeal tumors are characterized by frequent metastasis formation and local recurrence, which is the source of the unfavorable prognosis of this subtype. The aim of this study was to define chromosomal alterations associated with the aggressive behavior of hypopharyngeal tumors. METHODS: Twenty-nine head and neck squamous cell carcinomas (larynx n = 14 and hypopharynx n = 15) were analyzed by comparative genomic hybridization (CGH). Fluorescence in situ hybridization (FISH) was used to validate the CGH data and to compare the amplification pattern of the most frequently altered gene (cyclin-D1, CCND1) located on 11q13. RESULTS: The average number of genetic alterations was significantly higher in the hypopharyngeal tumors (P = 0.02). A good correlation of FISH and CGH data were seen. Gains on 11q13 were present in both subtypes, whereas amplification of CCND1 was associated with the aggressive phenotype by FISH. Chromosomal alteration, which was rarely detected in hypopharyngeal tumors but was observed in more than 50% of laryngeal carcinomas, was 8q gain. CONCLUSION: Our CGH and FISH data show that head and neck squamous cell carcinomas contain complex cytogenetic alterations and further support the hypothesis that different molecular pathways are responsible for the progression of differently localized tumors of the upper aerodigestive tract.


Assuntos
Aberrações Cromossômicas , Neoplasias Hipofaríngeas/diagnóstico , Neoplasias Hipofaríngeas/genética , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/genética , Idoso , Cromossomos Humanos Par 11/genética , Ciclina D1/genética , Feminino , Dosagem de Genes , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico
12.
Neurosci Lett ; 385(2): 93-8, 2005 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-15927369

RESUMO

Dopamine (DA), released from the lateral olivocochlear efferent fibers, is suggested to be neuroprotective against ischemia and noise exposure in the mammalian cochlea because it can reduce the postsynaptic excitotoxic effect of glutamate on the dendrite of the afferent auditory neuron. Using in vitro microvolume superfusion method on isolated guinea pig cochlea preparation, we found that the selective mGluR2/3 agonist (2R,4R)-aminopyrrolidine-2,4-dicarboxylic acid (2R,4R-APDC) significantly increased the release of DA in a dose-dependent manner. Other mGluR agonists, acting on groups I and III receptors (3,5-dihydroxyphenylglycine, amino-4-phosphonobutyric acid) and antagonists (2-methyl-6-(phenylethynyl)pyridine), (2S)-2-amino-2-(1S,2S-2-carboxycyclopronan-1-yl-3-(xanth9-yl)propanoic acid, alpha-methylserine-O-phosphate), were ineffective. The GABA(A) antagonist bicuculline (10microM) could antagonize the effect of 2R,4R-APDC suggesting that the mGluR-mediated enhancement of DA release was most likely attributable to a disinhibitory mechanism involving local GABAergic fibers. Bicuculline alone could also elevate the DA outflow indicating that cochlear GABA controls local DA release tonically. Our findings expand the view on the local effects of glutamate in the cochlea by showing the ability of the excitatory neurotransmitter to alleviate its own action on type I afferents via mGluRs and initiate a neuroprotective mechanism.


Assuntos
Cóclea/metabolismo , Dopamina/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Sinapses/metabolismo , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Cóclea/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Citoproteção/fisiologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Vias Eferentes/metabolismo , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas GABAérgicos/farmacologia , Antagonistas de Receptores de GABA-A , Cobaias , Células Ciliadas Auditivas Internas/efeitos dos fármacos , Células Ciliadas Auditivas Internas/metabolismo , Masculino , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/metabolismo , Terminações Pré-Sinápticas/metabolismo , Receptores de GABA-A/metabolismo , Receptores de Glutamato Metabotrópico/efeitos dos fármacos , Gânglio Espiral da Cóclea/efeitos dos fármacos , Gânglio Espiral da Cóclea/metabolismo , Sinapses/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos
13.
J Clin Oncol ; 23(15): 3421-32, 2005 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-15908653

RESUMO

PURPOSE: To investigate the clinicopathologic effects of local neoadjuvant Leukocyte Interleukin Injection (LI) regimen in oral squamous cell carcinoma (OSCC) patients. Treatment regimen included LI 800 IU/d as interleukin-2 (IL-2), administered half peritumorally and half perilymphatically five times per week for 3 weeks; low-dose cyclophosphamide; indomethacin; zinc; and multivitamins. PATIENTS AND METHODS: Thirty-nine patients diagnosed with T2-3N0-2M0 OSCC participated in the pathology portion of this phase II multicenter study (19 LI-treated patients and 20 historical controls). Clinical responses were determined by imaging. Paraffin-embedded tumor samples were obtained at surgery for all patients. Surgery for the LI-treated group was performed between days 14 and 54 after the end of treatment. Histologic evaluation, pathologic staging, necrosis, and American Joint Committee on Cancer grading were performed from hematoxylin and eosin sections. Immunohistochemistry and morphometry determined cellular infiltrate. RESULTS: Two pathologically complete, two major (> 50%), and four minor responses (> 30% but < 50%) resulted from LI treatment (overall response rate, 42%). Histopathology showed that the intratumoral CD4+:CD8+ ratio was low (< 1) in patients not treated with LI (controls). An increase in tumor-infiltrating CD4+ and a decrease of CD8+ T cells was observed in LI-treated patients, leading to a significantly (P < .05) higher intratumoral CD4+:CD8+ ratio (> 2.5). This was paralleled by dendritic cell transition from tumor surface toward stromal interface (P < .05), with macrophage decrease and neutrophil accumulation, multifocal microscopic necrosis, and significant (P < .05) increase in tumor stroma of LI-treated patients compared with controls. CONCLUSION: LI-treated OSCC patients were characterized by a markedly altered composition of tumor-infiltrating mononuclear cells, increased CD4+:CD8+ ratio, and increased tumor stroma to epithelial ratio, all of which were distinct from controls.


Assuntos
Relação CD4-CD8 , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Interleucina-2/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Carcinoma de Células Escamosas/mortalidade , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Imunoterapia/métodos , Indometacina/uso terapêutico , Injeções Intralesionais , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias Bucais/mortalidade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do Tratamento
14.
Cancer Metastasis Rev ; 24(1): 107-27, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15785876

RESUMO

Squamous cell cancer in the head and neck region (HNSC) is unique concerning its progression since it remains locoregional for long time and visceral metastases develop only in a later stage of the disease. Accordingly, molecular markers of the local invasion and the lymphatic dissemination both have critical importance. HNSC progression is associated with deregulated control of cell proliferation and apoptosis but it seems equally significant the disregulation of the proteolytic machineries. Here we outline the lymphatic metastatic cascade for HNSC to depict key molecular determinants as possible prognostic factors or therapeutic targets identifying immunological selection as a major feature. Unlike in local spreading, invasive potential of cancer cells seems to be less significant during lymphatic dissemination due to the anatomical properties of the lymphatic vessels and tissues. There is a general believe that HNSC is one disease however, data indicate that the anatomical localization of the tumor (the "soil") such as oral, lingual, glottic or pharyngeal has a significant effect on the gene expression profile and corresponding biological behavior of HNSC. Furthermore, even the endocrine milieu of the host was proved to be influential in modulating the progression of HNSC. Gene expression profiling techniques combined with proteomics could help to define and select usefull genetic and biomarkers of progression of HNSC, some of them could well be potential novel therapeutic target.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Animais , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Progressão da Doença , Perfilação da Expressão Gênica , Neoplasias de Cabeça e Pescoço/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Invasividade Neoplásica , Neovascularização Patológica
15.
Eur J Neurosci ; 18(6): 1439-47, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-14511324

RESUMO

Pseudorabies virus was used to label transneuronally descending auditory projections following intracochlear injections. At different time points after injection, virus-infected cells were detected immunohistochemically in the central nervous system. Initially (25 h), virus was transported retrogradely to olivocochlear cells in the pons. At 32-72 h after injection, labelling occurred in higher order auditory brainstem nuclei as well as in the locus coeruleus and pontine dorsal raphe. At 90-108 h, virus-infected neurons were found bilaterally in the medial geniculate body and in layer V of the auditory cortex. Viral transneuronal labelling in the auditory cortex after intracochlear application confirms the existence of a continuous descending chain of neurons from the auditory cortex to the cochlea, via the medial and lateral olivocochlear systems. The transneuronal labelling of the locus coeruleus and pontine dorsal raphe suggests that noradrenergic and serotonergic inputs may substantially influence the activity of olivocochlear cells, and thus the cochlea.


Assuntos
Vias Auditivas/virologia , Monoaminas Biogênicas/metabolismo , Cóclea/patologia , Herpesvirus Suídeo 1/metabolismo , Neurônios/metabolismo , Pseudorraiva/fisiopatologia , Animais , Córtex Auditivo/citologia , Córtex Auditivo/virologia , Cóclea/virologia , Lateralidade Funcional , Cobaias , Locus Cerúleo/anatomia & histologia , Locus Cerúleo/virologia , Masculino , Neurônios/virologia , Núcleo Olivar/citologia , Núcleo Olivar/metabolismo , Núcleo Olivar/virologia , Pseudorraiva/patologia , Núcleos da Rafe/anatomia & histologia , Núcleos da Rafe/virologia , Fatores de Tempo
16.
Laryngoscope ; 113(1): 120-4, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12514394

RESUMO

OBJECTIVES/HYPOTHESIS: Nasal polyps are benign mucosal protrusions into the nasal cavity of multifactorial origin and are characterized by chronic mucosal inflammation. The suggested multifactorial pathological mechanisms comprise several factors including cytokines and immunoglobulin E (IgE). The study was designed to examine the suggested roles of IgE, interleukin-5 (IL-5), and transforming growth factor-beta1 (TGF-beta1) in the pathogenesis of nasal polyposis. METHODS: Nasal polyps (n = 34) and healthy nasal mucosa samples (n = 9) were taken during routine endonasal surgeries. Immunoglobulin E (n = 13), IL-5 (n = 22), and TGF-beta1 (n = 27) concentrations were measured with enzyme-linked immunosorbent assay technique in homogenized polyp tissue and in control mucosa. Atopic and nonatopic groups were selected and compared. Histomorphological examination and immunohistochemical analysis to detect IL-5 and TGF-beta1 were performed in five specimens. RESULTS: The level of tissue-bound IgE was significantly higher in polyps compared with control specimens and in atopic compared with nonatopic polyps, but between nonatopic polyps and control specimens the difference was not significant. However, significant correlation was found between tissue and serum IgE in the complete polyp (P =.001) and atopic polyps group (P =.05). Tissue IL-5 concentration was significantly higher in polyps compared with control specimens, in which it was below the limit (15 pg/mL), and there was no difference between atopic and nonatopic polyps. In atopic polyps there was significant correlation between tissue IgE and IL-5. Transforming growth factor-beta1 concentration proved to be significantly higher in control mucosa than in polyps, with no difference between atopic and nonatopic polyps. Immunohistochemical analysis revealed numerous IL-5-positive eosinophil cells and TGF-beta1 positivity in the lamina propria of polyp samples, but none in control specimens. CONCLUSIONS: High tissue TGF-beta1 quantity in healthy nasal mucosa without its active form on the cell surface and its low quantity in polyps may reflect its essential role in the inhibitory mechanisms of nasal polyposis. Interleukin-5 plays a key role in the eosinophil recruitment and activation, and both atopic and nonatopic pathways might activate this process. The main sources of IL-5 and TGF-beta1 are the eosinophils and macrophages. Immediate hypersensitivity, besides other mechanisms, might be related to atopic polyps, but the involvement of other, local allergic mechanisms in IgE production of nonatopic polyp tissue cannot be excluded.


Assuntos
Imunoglobulina E/metabolismo , Interleucina-5/metabolismo , Mucosa Nasal/metabolismo , Pólipos Nasais/patologia , Fator de Crescimento Transformador beta/metabolismo , Adolescente , Adulto , Biomarcadores/análise , Biópsia por Agulha , Estudos de Casos e Controles , Técnicas de Cultura , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina E/análise , Imuno-Histoquímica , Interleucina-5/análise , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Pólipos Nasais/imunologia , Pólipos Nasais/cirurgia , Probabilidade , Prognóstico , Estudos de Amostragem , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Fator de Crescimento Transformador beta/análise , Fator de Crescimento Transformador beta1
17.
Int Tinnitus J ; 8(2): 108-10, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-14763221

RESUMO

Cochlear implantation has been performed for 16 years by investigators at Semmelweis University. During this period, different types of cochlear implants have been used and, in 30% of cases, hearing was observed to be restored in the nonimplanted ear. In addition to contralateral hearing improvement, significant improvement was observed in the caloric responsiveness of the nonoperated labyrinth. The preoperative median value of the average slow-phase velocity of the caloric test increased, and the increase was statistically significant on the contralateral side. The reason for this caloric response improvement is unclear, although possible explanations are brain plasticity or presently obscure trophic influence on the vestibular system. Whereas the role of brainstem function in the improvement of the contralateral ear's caloric response remains unclear it is also possible that hearing impulses affect the labyrinth. Clearly, the influence of cochlear implants on vestibular function requires further investigation to explain the improvement of contralateral vestibular responsiveness.


Assuntos
Implante Coclear , Surdez/terapia , Audição/fisiologia , Vestíbulo do Labirinto/fisiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Implantes Cocleares , Surdez/etiologia , Eletronistagmografia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios
18.
Magy Onkol ; 44(3): 239-245, 2000 Oct 01.
Artigo em Húngaro | MEDLINE | ID: mdl-12050753

RESUMO

A recent survey of head and neck cancer indicated a sharp difference in survival between cancer of the hypopharyx and cancers formed in other head and neck sites. We have analyzed tumor size relative to clinical stage and vascularization as possible causes for such a difference in a series of 21 patients with cancers of the laryngopharynx (11 glottic and 10 hypopharyngeal). We found that the volume of the smallest cancers of the larynx at stage 2 are significantly larger than the volume of the cancers of the hypopharynx at stage 4 (p<0.05). Next, we have determined by immunohistochemistry and morphometry the microvessel density (MVD), microvessel perimeter (MVP) and VEGF expression of laryngo-hypopharyngeal cancers. Analysis of these data indicates that there is no difference in vascularization and VEGF expression between these two tumor types. These data strongly suggest that the invasive-but not the angiogenic phenotype of hypopharyngeal cancer cells could be responsible for the more aggressive biological behavior of this head and neck cancer subtype.

19.
Pathol Oncol Res ; 2(1-2): 43-47, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-11173582

RESUMO

The authors differentiate cancer types of the glottis setting out from the free margin or the ventricular surface of the true vocal cord. The latter is considered to be a reliant clinicopathological unit starting from the dividing line of the stratified-ciliated epithelium margins, whereas the so called junctional tumor differs in its histogenesis and invasivity. They give a detailed description of intralaryngeal extension of these tumours on the basis of histopathological investigations.

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