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BACKGROUND: Laryngopharyngeal reflux (LPR) disease has many symptoms such as globus pharyngeus, excessive throat clearing and hoarseness. The aim of this study was to investigate the effect of stellate ganglion block (SGB) in addition to proton pump inhibitors (PPI) on LPR. METHODS: Fifty patients complaining of more than 3 typical LPR symptoms for over 3 months were enrolled in the study. The P group took PPI for 8 weeks. The SP group took PPI and interwent a series of 8 SGB procedure once a week during the period of treatment. The blocks were performed one at a time unilaterally on the right and left stellate ganglions by injecting 1% mepivacaine 6 ml. We evaluated the reflux symptom index (RSI) before treatment and following 4 weeks and 8 weeks of treatment in both groups. RESULTS: After 4 weeks of treatment, the RSI of the P group decreased, but not significantly, to 16.6 +/- 6.8 compared with the baseline value of 19.2 +/- 2.7 (P = 0.093), whereas the RSI of the SP group decreased significantly to 9.8 +/- 3.3 compared with the baseline value of 19.0 +/- 4.7 (P = 0.000). After 8 weeks of treatment, the RSI of the P group decreased significantly to 13.7 +/- 6.7 (P = 0.001) and the RSI of the SP group also decreased significantly to 7.7 +/- 3.4 (P = 0.000). There were significant differences in the RSI between the two groups after 4 weeks (P = 0.000) and 8 weeks (P = 0.001) of treatment. CONCLUSIONS: The symptoms of LPR improved earlier when PPI therapy was combined with SGB compared with PPI therapy alone.
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Humanos , Rouquidão , Refluxo Laringofaríngeo , Mepivacaína , Faringe , Inibidores da Bomba de Prótons , Gânglio EstreladoRESUMO
OBJECTIVES: The transoral removal of stones by sialodochoplasty has been popularized in the treatment of submandibular sialolithiasis. However, the effectiveness of sialodochoplasty is controversial, and there are no reports on the long-term outcomes of this procedure. The purpose of this study was to assess the effectiveness and long-term outcomes of sialodochoplasty in patients with submandibular sialolithiasis. METHODS: We conducted a cross-sectional study that included retrospective chart reviews and prospective telephone or interview surveys of 150 patients treated for submandibular sialolithiasis from March 2001 to January 2008. The patients were treated with two different procedures by two different surgeons. One surgeon performed a transoral sialolithectomy without sialodochoplasty in 107 patients (SS group), and the other surgeon performed a transoral sialolithectomy with sialodochoplasty in 43 patients (SP group). RESULTS: The success rate of transoral sialolithectomy was 98.1% in the SS group and 93% in the SP group. The recurrence rates of symptoms or stones were 1.9% and 4.7% in the SS and SP groups, respectively. The incidence of postoperative transient hypoesthesia was 13.1% in the SS group and 34.9% in the SP group. The mean operating times were 29.79 and 47.44 minutes in the SS and SP groups, respectively. The mean percentage of general anesthesia was 42.1% in the SS group and 83.7% in the SP group. CONCLUSION: Sialodochoplasty in addition to transoral sialolithectomy for submandibular sialolithiasis did not affect the rate of symptom or stone recurrence, but did increase the postoperative hypoesthesia incidence and general anesthesia percentage.
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Humanos , Anestesia Geral , Estudos Transversais , Hipestesia , Incidência , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Cálculos das Glândulas Salivares , TelefoneRESUMO
Peripheral T cell neoplasms (PTCNs) comprise a group of uncommon and heterogenous lymphoid malignancies. They are more difficult to diagnose and treat and have a worse prognosis than B cell lymphomas. NK/T cell lymphoma is the most common histologic subtype in the head and neck. Unspecified type is the most common subtype of PTCNs but is not reportedin oral cavity or nasal cavity. We report a case of a perforating palatal ulceras a rare presentation of peripheral T cell lymphoma with a review of literature.
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Actinomicose , Cabeça , Linfoma , Linfoma de Células B , Linfoma de Células T Periférico , Boca , Cavidade Nasal , Pescoço , Palato Duro , Prognóstico , ÚlceraRESUMO
Although liposarcomas are second most frequently encountered sarcomas that occur in soft tissue, liposarcomas of the head and neck are very uncommon. Liposarcomas of the retropharyngeal space are rare and do not cause symptoms until they reach a large size to cause mass effect. Depending on the location of the pharyngeal tumor, patients may present with foreign body sensation on throat, swallowing difficulty, respiratory difficulty, a painless neck mass, or obstructive sleep apnea. Recently we have experienced a case of retropharyngeal liposarcoma causing obstructive sleep apnea, so we report our clinical experiences with a brief review of literature.
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Humanos , Deglutição , Corpos Estranhos , Cabeça , Lipossarcoma , Pescoço , Faringe , Sarcoma , Sensação , Síndromes da Apneia do Sono , Apneia Obstrutiva do SonoRESUMO
Eosinophilic otitis media is characterized by thickened, bulging and pale tympanic membrane with viscous or gelatinous secretion in the middle ear cavity. Gelatin-like fluid contains many eosinophils and this disease may occur in patients with adult onsetbronchial asthma. It is intractable otitis media which resists all therapy including myringostomy and tympanomastoidectomy due to abnormal mucosa until the allergic factor is controlled. In these patients, oral steroid is very effective in controlling the disease. Major complication of eosinophilic otitis media is sensorineural hearing loss which may occur despite steroid therapy. We report two cases of patients with bilateral otitis media with bronchial asthma, which were treated with oral and topical steroid therapies.
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Adulto , Humanos , Asma , Orelha Média , Eosinófilos , Fibrinogênio , Gelatina , Perda Auditiva Neurossensorial , Mucosa , Otite Média com Derrame , Otite Média , Otite , Membrana TimpânicaRESUMO
BACKGROUND AND OBJECTIVES: Septal surgery is one of the common causes of nasal septal perforation. In cases of bilateral septal mucosal tearings, autologous cartilage is usually inserted between the injured mucosa. Additionally, we applied the fibrin glue on the margin of injured mucosal surface for the fixation of inserted cartilage and for the promotion of mucosal regeneration. The aim of this study was to evaluate the efficacy of this method in the prevention of nasal septal perforation. SUBJECTS AND METHOD: A total 378 cases of septal surgery was performed during past 2 years. Bilateral septal mucosal injuries at the corresponding area occurred in 32 patients. In group 1 (23 patients), autologous cartilage was inserted between the injured mucosa. In group 2 (9 patients), autologous cartilage was inserted and fibrin glue was applied on the mucosal margin of cartilage insertion site. We compared the perforation rate between two groups. RESULTS: In group 1, nasal septal perforation occurred 8 of 23 patients (34.7%) and in group 2, 1 of the 9 patients (11.1%) had perforation. Although the occurrence rate of perforation was significantly lower in group 2, statistical significance between two groups were absent because of the small number of patients who experienced the septal perforation. CONCLUSION: The application of fibrin glue after cartilage insertion at the defect site is thought to be very useful in the prevention of nasal septal perforation. We report these results as a preliminary data for the future study about the usefulness of fibrin glue in the prevention of nasal septal perforation.
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Humanos , Cartilagem , Adesivo Tecidual de Fibrina , Fibrina , Mucosa , Perfuração do Septo Nasal , RegeneraçãoRESUMO
BACKGROUND AND OBJECTIVES: In hemithyroidectomy, most surgeons don't care about postoperative hypothyroidism because of the remaining functioning contralateral thyroid lobe, but the incidence of hypothyroidism after hemithyroidectomy is reported from 5 to 35%. The purpose of this study was to assess the incidence, natural history, factors contributing to hypothyroidism after hemithyroidectomy. SUBJECTS AND METHOD: 212 consecutive cases of hemithyroidectomized patients diagnosed from Feb. 2001 through Dec. 2004 were retrospectively analyzed. One hundred thirty-six of 212 cases were enrolled in this study after the exclusion criteria applied. The definition of postoperative hypothyroidism was based on serum TSH and free T4 level. The relationship between hypothyroidism and several factors, such as mean age, sex, preoperative free T4, TSH, microsomal antibody, thyroglobulin antibody levels and lymphocytic infiltration of the resected gland, were stastically analyzed. RESULTS: The fifty eight of 136 patients (42.6%) became biochemical hypothyroidism postoperatively. Among them, 11 patients (8.1%) showed overt hypothyroidism and 47 patients (34.5%) showed subclinical hypothyroidism. In postoperative hypothyroid group, preoperative TSH, microsomal and thyroglobulin Ab levels and lymphocytic infiltration were significantly higher than in postoperative euthyroid group (p<0.05). The odds ratio of preoperative microsomal Ab, thyroglobulin Ab level and lymphocytic infiltration of resected gland was 17.18, 3.01 and 2.26 folds, respectively. CONCLUSION: In this study, we confirmed that there was unexpectedly high incidence of postoperative hypothyroidism after hemithyroidectomy. We propose that preoperative high TSH level, positive microsomal Ab, thyroglobulin Ab and marked lymphocytic infiltration of resected gland could be predicitive factors of postoperative hypothyroidism after hemithyroidectomy.
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Humanos , Hipotireoidismo , Incidência , História Natural , Razão de Chances , Estudos Retrospectivos , Tireoglobulina , Glândula Tireoide , TireoidectomiaRESUMO
BACKGROUND AND OBJECTIVES: With the recent introduction of a routine calcium screening, the incidence of parathyroid adenoma, a rare disease but also the most frequent cause of primary hyperparathyroidism, has increased. The increased incidence, however, has not been met readily by ENT surgeons since the clinical symptoms, diagnostic and operative techniques of the disease are not familiar to them. The purpose of this study was to assess the clinical characteristics, effectiveness of preoperative localization test and surgical outcomes of parathyroid adenoma with primary hyperparathyroidism. SUBJECTS AND METHOD: Ten consecutive cases of parathyroid adenoma with hyperparathyroidism surgically treated from Jun. 2001 through Jan. 2005 were included in this study. Preoperative localization test was performed with combinations of radionuclide parathyroid scan, ultrasonography and CT scan. Intact parathyroid hormone (iPTH), total calcium, phosphate, alkaline phosphatase were checked before and after surgery. RESULTS: The clinical manifestations were osteoporosis (90%), neuromuscular symptoms (70%), peptic ulcer (60%), ureter stone (60%) and renal stone (40%) in order of frequency. Diagnosis was delayed in most of the patients for 1 to 9 months because of their nonspecific symptoms. Sensitivities of parathyroid scan, neck ultrasonography and neck CT as preoperative localization test were 80%, 85.7% and 80%, respectively. The most common postoperative complication was temporary hypocalcemia due to hungry bone syndrome. It was easily corrected by calcium and vitamin D supplements. CONCLUSION: We reconfirmed that parathyroid adenoma with hyperparathyroidism needed to be presented as a systemic disease with numerous clinical features, and therefore, a team approach involving an endocrionolgist would be essential. Surgical treatment via unilateral approach for preoperatively localized single parathyroid adenoma was successful without any complications, but a prospective randomized study is needed.
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Humanos , Fosfatase Alcalina , Cálcio , Diagnóstico , Hiperparatireoidismo , Hiperparatireoidismo Primário , Hipocalcemia , Incidência , Programas de Rastreamento , Pescoço , Osteoporose , Hormônio Paratireóideo , Neoplasias das Paratireoides , Paratireoidectomia , Úlcera Péptica , Complicações Pós-Operatórias , Doenças Raras , Tomografia Computadorizada por Raios X , Ultrassonografia , Ureter , Vitamina DRESUMO
BACKGROUND AND OBJECTIVES: In patients with extensive polyposis of maxillary sinus or antrochoanal polyp, it is very difficult to remove entire diseased mucosa through middle meateal antrostomy and often require the procedure of canine fossa puncture. The aim of this study was to analyze the complications associated with this procedure. MATERIALS AND METHOD: We performed a prospective study and questionnaire about complications on 56 patients who had undergone a canine fossa puncture and removal of diseased mucosa with microdebrider. RESULTS: A total of 91 canine fossa punctures were performed in 56 patients. Twenty five patients (44.6%) experienced more than one adverse effect. The most common complaint was facial or cheek swelling (29.7%) followed by facial or cheek pain (24.8%), facial bruise (17.9%), facial numbness (11.9%), dental numbness (7.9%), tingling sensation (5.9%) and infection of puncture site (1.9%). Most complications (94.1%) resolved within 4 weeks after surgery. Only one patient (0.9%) had persistent facial numbness even at 14 months after the procedure. CONCLUSION: Removal of extensive polyposis and diseased mucosa of the maxillary sinus with microdebrider through canine fossa puncture is a very useful technique. However, a significant number of patients experience temporary or permanent complications after surgery. Surgeons should be aware of these side effects and inform the patients before performing the surgical procedure.
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Humanos , Bochecha , Contusões , Endoscópios , Hipestesia , Seio Maxilar , Mucosa , Pólipos , Estudos Prospectivos , Punções , Inquéritos e Questionários , SensaçãoRESUMO
BACKGROUND AND OBJECTIVES: Completion thyroidectomy (CT) is defined as the resection of residual thyroid tissue following the initial operation of less than a total thyroidectomy. But completion thyroidectomy is a rare surgical procedure associated with increased morbidity and is related to recurrent laryngeal nerve injury and hypoparathyroidism. The purpose of present study is to evaluate the various clinical and pathological situation of completion thyroidectomy (CT) and the safety of completion thyroidectomy (CT) according to various parameters. SUBJECTS AND METHOD: From February 2001 through July 2005, 32 consecutive cases who underwent completion thyroidectomy (CT) were retrospectively analyzed. Prophylactic CT was performed in 17 cases and therapeutic CT was performed in 15 cases. Their mean follow-up was 19.8+/-0.6 months (3-44 months). The various parameters were retrospectively analyzed between two groups. These parameters included the time interval between the first and second operations, complication associated with CT, duration of hospital stay, preoperative imaging, preoperative fine needle aspiration cytology, frozen biopsy and permanent pathology. RESULTS: Prophylactic CT was composed of ten cases of follicular carcinoma and seven cases of papillary carcinoma. Therapeutic CT was composed of four cases of papillary carcinoma, one case of follicular carcinoma and 10 cases of benign nodule. The time interval between the first and second operations was 48.9+/-1.3 days (prophylactic CT) and 15.1+/-.8 years (therapeutic CT). The duration of hospital stay was not significantly different between two groups. Transient hypocalcemia occurred in 11.8% (2/17, prophylactic CT) and 13.3% (2/15, therapeutic CT), respectively. Permanent hypocalcemia occurred in 5.9% (1/17, prophylactic CT) and 6.7% (1/15, therapeutic CT). Recurrent laryngeal nerve injury occurred in 0% (0/17, prophylactic CT) and 13.3% (2/15, therapeutic CT) Hypocalcemia was not significantly different between two groups, but the difference of recurrent laryngeal nerve injury was significant. CONCLUSION: Completion thyroidectomy might be a safe operation with minimal morbidity. However, in those therapeutic CT cases where previous operation records are unavailable, special care was needed in preserving the recurrent laryngeal nerve and parathyroid gland. We also suggest that even in unilateral thyroidectomy, the parathyroid gland should be preserved.
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Biópsia , Biópsia por Agulha Fina , Carcinoma Papilar , Seguimentos , Hipocalcemia , Hipoparatireoidismo , Tempo de Internação , Glândulas Paratireoides , Patologia , Nervo Laríngeo Recorrente , Traumatismos do Nervo Laríngeo Recorrente , Estudos Retrospectivos , Glândula Tireoide , TireoidectomiaRESUMO
Branch retinal vein occlusion(BRVO) is the most frequent entity of retinal vascular abnormality following diabetic retinopathy; a review of diagnosis for all our new outpatients verifies this, Sudden loss of visual acuity occur in the vast majority of BRVO patients. Other complications are macular edema, capillary nonperfusion, neovascularization, vitreous hemorrhage and so on. We did a clinical analysis of 71 patients with BRVO(71 eyes), who were considered to be treated with laser photocoagulation to prevent vitreous hemorrhage. We confirmed the fact that laser photocoagulation could prevent vitreous hemorrhage to a significant degree, but we were unable to demonstrate any statistical correlation between the occurrence of vitreous hemorrhage and the time of laser photocoagulation.
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Humanos , Argônio , Capilares , Retinopatia Diabética , Diagnóstico , Fotocoagulação , Edema Macular , Pacientes Ambulatoriais , Veia Retiniana , Retinaldeído , Acuidade Visual , Hemorragia VítreaRESUMO
Deep neck infections affect fascial compartment of the head and neck, and their contents. Fever, pain, and swelling are the most common presenting symptoms. Also, the development of septic shock or mediastinitis depends on the degree of progression of the disease. The advent of antibiotics decreases the incidence and mortality of the deep neck infection. Antibiotics also alters the causation and management of this disease. In a recent report, mixed species with anaerobe were found in 50% of patients, whereas Staphylococci and Hemolytic streptococci were the leading causes of deep nect infections in the past. Also, in the case of immunocompromised host, deep neck infections caused by tuberculosis or fungus are not excluded. We experienced a 23 year old man with deep neck infection caused by tuberculosis presenting bone destruction of cervical spine. In this article, we reviewed the etiology, diagnosis, and treatment of this case, with a review of literatures.
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Feminino , Humanos , Adulto Jovem , Antibacterianos , Vértebras Cervicais , Diagnóstico , Febre , Fungos , Cabeça , Hospedeiro Imunocomprometido , Incidência , Mediastinite , Mortalidade , Pescoço , Abscesso Retrofaríngeo , Choque Séptico , Coluna Vertebral , TuberculoseRESUMO
Frosted branch angiitis menifests with acute visual loss in an otherwise young healthy patient. The fundus findings are dramatic and characterized by severe white sheathing of the retinal vessels. A variable amount of anterior chamber and vitreous inflammation also occur. Fluorescein angiography demonstrates leakage of dye from the retinal vessels with no evidence of vascular stasis or occlusion. The clinical findings respond dramatically to systemic corticosteroids. The authors experienced a case of frosted branch angiitis which occured in 5year-old female whose fundus findings were marked white sheathing and macular thicking.
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Feminino , Humanos , Corticosteroides , Câmara Anterior , Angiofluoresceinografia , Inflamação , Vasos Retinianos , VasculiteRESUMO
No abstract available.
Assuntos
Adulto , Humanos , Coelhos , Pulmão , Células Epiteliais Alveolares , PneumonectomiaRESUMO
BACKGROUND: Status epilepticus (SE) shows stereotyped progression of electroencephalogram (EEG) and behaviors in human and some SE models. We analysed semiologic features with the electroencephalographic characteristics of kainic acid (KA)-induced SE which showed different patterns from the previously reported patterns of SE. METHODS: Seventeen male Sprague-Dawley rats weighing 150~220 grams were used. SE was induced 5~7 days after the place-ment of epidural electrodes on the rats, using 13 mg/kg kainic acid I.p.. EEGs were recorded and behaviors were contin-uously observed until the end of SE. RESULTS: After the initial akinesia which was apparent within minutes of the KA injection, limbic motor seizure (LMS) composed of facial clonus, head nodding, and akinesia were repeated. Each LMS progressed into more vigorous patterns composed of facial clonus, head nodding, bilateral upper extremity clonus and rearing, without akinesia. Each cycle was repeated as the SE progressed. Severe LMS made up of facial clonus, head nodding, bilateral upper extremity clonus, rearing, falling, and jumping was followed and reiterated. After severe LMS, rats entered subtle SE. In the EEG, repeated discrete seizures mostly consisted of low voltage regular sharp waves and spikes with flat periods. After entering into the LMS, discrete seizure, merging seizure, continuous ictal discharges & periodic epileptiform discharges (PEDs) appeared sequentially in a single cycle and also reiterated. Even during subtle SE, rhythmic cycles were composed of alternating continuous ictal discharges and PEDs. PEDs were gradually replaced by sharp waves or spikes and rats recovered from SE. CONCLUSIONS: Semiologic features and the EEG sequence of KA-induced SE were composed of a series of rhythmic cycles, which have separate EEG patterns in a single cycle. Late EEG patterns of SE were more prominent as the SE progressed.
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Animais , Humanos , Masculino , Ratos , Eletrodos , Eletroencefalografia , Cabeça , Ácido Caínico , Ratos Sprague-Dawley , Convulsões , Estado Epiléptico , Extremidade SuperiorRESUMO
BACKGROUND: Refractory status epilepticus (RSE) requires urgent and effective treatment. Recently, midazolam was suggested as a useful drug in controlling RSE. In order to evaluate the effectiveness and adverse effects of midazolam, we compared midazolam with thiopental sodium. METHODS: Fourteen consecutive RSE in 13 patients from January 1998 to August 1999 were treated. Two RSE were happened in one patient. When the SE was refractory as a result of standard treatment, midazolam and thiopental sodium was alternatively used as therapeutic agent. RESULTS: Out of 9 RSE treated with midazolam, 5 were resolved. Four unresolved RSE received additional thiopental sodium. Thiopental sodium was initially administered in 5 out of 14 RSE. Among the 5 RSE improved by midazolam, no one had midazo-lam- induced hypotension or pneumonia. Three patients had respiratory suppression and needed artificial ventilation. RSE was controlled in 2 out of 4 patients treated with thiopental sodium after midazolam. In these patients, hypoten-sion was developed in 3, pneumonia in 2, and respiratory suppression in all. In 5 RSE treated with thiopental sodium alone, RSE were successfully treated in 3 patients. Complications were hypotension in 2, pneumonia/unknown infec-tion in 3, and respiratory suppression in 4. CONCLUSIONS: Midazolam was comparably effective as thiopental sodium in the treatment of RSE, with less adverse effects. We suggest that midazolam be used in the treatment of RSE before thiopental sodium is administered.
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Humanos , Hipotensão , Midazolam , Pneumonia , Estado Epiléptico , Tiopental , VentilaçãoRESUMO
BACKGROUND: Nonlinear mutual cross prediction (MCP) characterizes dynamic interdependence among nonlinear systems. MCP also reveal relative strength of the coupling between systems, thus provides information about the direc-tion of interdependence. The aim of this study is to apply MCP algorithm to multi-channel EEG and to characterize spatio- temporal pattern of seizure. METHODS: We analyzed MCP of EEG of three medically intractable temporal lobe epilepsy patients, who underwent temporal lobectomy (left 2, right 1). Asymmetry of nonlinear cross predictability between channels was investigated. Five epochs of interictal EEG free from epileptiform discharge(s) and of ictal EEG were analyzed. RESULTS: In interictal period, both frontal and occipital region appeared a weak driving force while awake and this driving force was further weakened during sleep. Before the onset of the seizure (preictal phase), the intensity of driving system became slightly stronger around seizure foci in 3 out of 8 seizures while no significant change was seen on the naked eyes. However this change was dim and not continuous. At the onset of seizure (ictal phase), 5 out of 8 seizures showed strong driving force around seizure foci. Three seizures without significant change initially had strong driving force as synchronous seizure discharges became built-up and spreading to surrounding areas in the middle of seizure. All seizures showed ipsilateral frontotemporal strong driving force and centroparietal response system, which was typical spatio-temporal distribution of MCP. CONCLUSION: MCP analysis may be a useful method for detecting spatio-temporal distribution and propagation pattern in temporal lobe epilepsy.
Assuntos
Humanos , Eletroencefalografia , Epilepsia do Lobo Temporal , Convulsões , Lobo TemporalRESUMO
BACKGROUND: Immediate early gene (IEG) is supposed to be linked in the continuous seizure induced long-term changes of specific neurons. We tried to investigate the effects of focal interictal epileptiform discharges on the c-JUN expression in the rat brain which is not clearly understood. METHODS:Epidural electrodes were placed on a male Sprague-Dawley weighing 150~230 g and benzathine penicillin (Pc) was applied cortically. After focal interictal epileptiform discharges were successfully identified, EEG was recorded regularly. Cardiac perfusion and extraction of the brain was done at 2, 4, 24 hours and 1 week after the Pc application. Sixteen rats were evenly distributed into 4 groups. Immunocytochemical staining with specific antisera (Santa Cruz) was performed. RESULTS: The epileptiform discharges were induced within an hour after topical Pc applications. At 2 hours after Pc application, c-JUN was moderately expressed in the dentate gyrus (DG) and weakly expressed in the CA3 pyramidal cell, amygdala, pyriform cortex, thalamus, and neocortex. At 4 hours, c-JUN was minimally expressed in DG and other regions. Whereas, at 24 hours, c-JUN was maximally expressed in the DG and also in the CA3 pyramidal cell, amygdala, pyriform cortex, thalamus, and neocortex. One week after Pc application, c-JUN was moderately expressed in the DG and weakly expressed in the CA3 pyramidal cell, amygdala, pyriform cortex, and neocortex. CONCLUSIONS: This data showed that even focal interictal epileptic activity can induce IEG encoded c-JUN protein in the specific distant brain regions of a rat until a late period and the expression pattern showed a synchronous and bimodal pattern.