Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo

BACKGROUND: In mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN). Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions. METHODS: We examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2) gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC) knock-in mice using a real-time bioluminescence measurement system. RESULTS: Administration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms. CONCLUSION: These findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

Effect of Resveratrol, a SIRT1 Activator, on the Interactions of the CLOCK/BMAL1 Complex

BACKGROUND: In mammals, the CLOCK/BMAL1 heterodimer is a key transcription factor complex that drives the cyclic expression of clock-controlled genes involved in various physiological functions and behavioral consequences. Recently, a growing number of studies have reported a molecular link between the circadian clock and metabolism. In the present study, we explored the regulatory effects of SIRTUIN1 (SIRT1), an NAD+-dependent deacetylase, on CLOCK/BMAL1-mediated clock gene expression. METHODS: To investigate the interaction between SIRT1 and CLOCK/BMAL1, we conducted bimolecular fluorescence complementation (BiFC) analyses supplemented with immunocytochemistry assays. BiFC experiments employing deletion-specific mutants of BMAL1 were used to elucidate the specific domains that are necessary for the SIRT1-BMAL1 interaction. Additionally, luciferase reporter assays were used to delineate the effects of SIRT1 on circadian gene expression. RESULTS: BiFC analysis revealed that SIRT1 interacted with both CLOCK and BMAL1 in most cell nuclei. As revealed by BiFC assays using various BMAL1 deletion mutants, the PAS-B domain of BMAL1 was essential for interaction with SIRT1. Activation of SIRT1 with resveratrol did not exert any significant change on the interaction with the CLOCK/BMAL1 complex. However, promoter analysis using Per1-Luc and Ebox-Luc reporters showed that SIRT1 significantly downregulated both promoter activities. This inhibitory effect was intensified by treatment with resveratrol, indicating a role for SIRT1 and its activator in CLOCK/BMAL1-mediated transcription of clock genes. CONCLUSION: These results suggest that SIRT1 may form a regulatory complex with CLOCK/BMAL1 that represses clock gene expression, probably via deacetylase activity.

Characteristics of Deep Neck Infections in Pediatric Patients Compared with Adults / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The purpose of this article was to investigate the difference of clinical manifestations in deep neck infections between pediatric patients and adult patients and to consider their respective treatment. SUBJECTS AND METHOD: The author reviewed the experience of 158 patients with deep neck infections from 1995 to 2004. Peritonsillar abscess, superficial infection, and infections related to external neck wound and head and neck tumors were excluded. Among 158 patients, 43 patients were children. To find out the characteristics of deep neck infection with pediatric patients, the author compared these patients with adult patients using student t-test and chi-square test. RESULTS: Compared with adult patients, pediatric patients with deep neck infections were found to have less dysphagia as a symptom, lower complication rate, fever higher than 38degrees C, and the white blood cell count of more than 15,000/mm3 (p0.05). CONCLUSION: The author suggests that the prognosis of the pediatric patients with deep neck infections seems to be relatively good compared with adult patients and the severity of the disease should not be overestimated on the ground of high fever or white blood cell count.

A Case of Ancient Schwannoma Masquerading as Originating from Cervical Spinal Nerve / 대한이비인후과학회지

Schwannoma is a benign, solitary, and slow growing tumor which may arise from the nerve sheath of the peripheral, sympathetic, and cranial nerves. Ancient schwannoma is a rare variant of schwannoma with atypical tumor cells with nuclear pleomorphism and hyperchromatism. It may be confused with a malignant mesenchymal tumor or schwannoma with malignant transformation. We report a case of an ancient schwannoma being adjacent to the transverse process of the fourth cervical spine.

A Case of Adenoid Cystic Carcinoma of the Nasal Septum Misdiagnosed as Pleomorphic Adenoma / 대한이비인후과학회지

Adenoid cystic carcinoma is one of the most common minor salivary gland malignancies of the paranasal sinuses and nasal cavity and has a propensity for frequent local recurrencesand distant metastasis. It sometimes has variable histopathologic patterns in the same tumor, which makes diagnosis difficult. A very rare case of adenoid cystic carcinoma of the nasal septum, initially thought to be pleomorphic adenoma, is presented along with a review of the literature.

Predisposing Factors of Complicated Deep Neck Infection: An Analysis of 158 Cases

Both the introduction of antibiotics and improvements in oral hygiene have made deep neck infections occur less frequently today than in the past. Nevertheless, the complications from these infections are often life-threatening. The purpose of this article was to review the clinical findings of deep neck infections and identify the predisposing factors of these complications. The present study reviewed 158 cases of deep neck infections between the years of 1995 to 2004, 23 of which had life-threatening complications. Cases were excluded if they had peritonsillar abscesses, superficial infections, infections related to external neck wounds, or head and neck tumors. The authors used multiple linear regression and the logistic regression analysis in order to determine the clinical parameters that are associated with longer hospitalizations and complicated deep neck infections, respectively. The multiple linear regression showed that patients with a large number of involved spaces, diabetes mellitus, and complications required longer hospitalizations (p < 0.05). The logistic regression showed that patients with more than two involved spaces were more likely to have complicated deep neck infections (p < 0.05). Patients with odontogenic causes had negative correlation (p < 0.05). We recommend that high-risk groups, such as diabetic patients and/or patients with more than two involved spaces, should be more closely monitored throughout their hospitalization.

A Case of Vocal Cord Candidiasis / 대한이비인후과학회지

Candidal infection is recently reported to increase in certain predisposing condition, although isolated candidiasis from larynx is infrequently recognized and reported. Iisolated whitish lesions of vocal cord may be confused with precancerous lesions, squamous cell carcinoma, or verrucous carcinoma. A 62-year-old male visited our department for continuous hoarseness. Flexible laryngoscopy disclosed a whitish irregular exophytic mucosal lesion in right true vocal cord, which extended to anterior commissure and subglottis. Laryngeal microscopic surgery was done because of a concern regarding the possibility of glottic cancer. A pathologic biopsy revealed distorted and septated hypae and yeasts, scattered in moderate dysplasia. The patient was treated with itraconazole for 4 weeks, and followed up without any recurrence of candidiasis or dysplasia.

The Effect of Postural Restrictions in the Treatment of Benign Paroxysmal Positional Vertigo / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The treatment of Benign Paroxysmal Positional Vertigo (BPPV) consist of repositioning maneuver in order to remove otolithic debris, and subsequent postural restrictions to prevent debris from reentering into the canal. But, it is doubtful how much postural restrictions could have an effect on the final outcomes of BPPV. The purpose of this study is to find out the effect of postural restrictions when imposed on as one of the treatment methods of BPPV, out-broken due to otolithic debris in the posterior semicircular canal, and to find out the necessity of postural restrictions. SUBJECTS AND METHOD: Seventy cases diagnosed as BPPV of the posterior semicircular canal were studied. All the patients were treated by modified Epley Maneuver. They were divided into two groups. The first group (group A, 35 patients) was instructed to sleep in a semi-sitting position and not to move their heads forward or backward, whereas the second group (group B, 35 patients) was not taught to do any specific thing. The gathered information from all the patients was analyzed by age of onset, gender, duration of the disease, and cure rates or recurrence rates. RESULTS: In group A, the average age was 54.5 years and mean duration of symptoms was 116.5 days. On the other hands, in the group B, the average age and the mean duration was 54.8 years and 86.7 days, respectively. The cure rates of the group A and B were 91.4% and 94.3%, respectively. The recurrence rates were 12.5% and 9.1% for group A and group B patients, respectively. No statistically significant difference was found between two groups regarding patient age, duration of symptoms, and cure rates or recurrence rates. CONCLUSION: From the analysis of this study, it can be said that postural restrictions imposed after the repositioning maneuver do not have a significant effect on the final outcomes of BPPV, so they are not recommendable.

Management of Cerebrospinal Fluid Rhinorrhea / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The cerebrospinal fluid rhinorrhea usually occurs as a result of trauma or surgical procedure such as endoscopic sinus surgery, neurosurgery and its incidence has shown tendency to increase recently. This study demonstrates the outcome of the treatment method of 24 CSF rhinorrhea cases. SUBJECTS AND METHOD: We reviewed the medical records of 24 patients treated at Chonnam National University Hospital from 1994 to 2003. RESULTS: The most common cause of cerebrospinal fluid rhinorrhea was iatrogenic trauma. The most common site was ethmoid. The treatment methods were selected according to the cause, interval to treatment, underlying diseases and subjective symptoms. In our review were conservative treatments only or operations such as endoscopic approach and external ethmoidectomy. The overall success rate was 91% (22/ 24). CONCLUSION: Management and repair of cerebrospinal fluid rhinorrhea should be individualized.

A Case of Dural Arteriovenous Fistula with Multitudinous Feeders Treated by Transvenous Embolization / 대한이비인후과학회지

Dural arteriovenous fistula (DAVF) is an uncommon condition. However, it is important for otologists because it is the most common cause of pulsatile tinnitus and may also present with intracranial hemorrhage and neurological disturbance. Many therapeutic approaches, such as surgery and endovascular techniques, have been proposed to obliterate the lesions. Surgery may be accompanied by massive blood loss. Transarterial embolization seldom obliterates transverse-sigmoid sinus DAVFs completely and permanently. In recent years, several authors have reported the effect of transvenous embolization of transverse-sigmoid sinus DAVFs in English literature. We recently experienced a case of sigmoid DAVF treated by transvenous embolization and report it with a review of the literature.

Studies on Relationships between Inflammatory Cell, Cytokines and Clinical Features in Pediatric Otitis Media with Effusion / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Retension of inflammatory cells and cytokines in the middle ear cleft can result in ongoing chronic otitis media with effusion. This study aims to investigate the role of these inflammatory cells and cytokines in the middle ear effusion (MEE) of children with otitis media with effusion. MATERIALS AND METHOD: We analyzed 46 pediatric middle ear effusion samples for IL-6, IL-10, TNF-alpha and inflammatory cells and tried to elucidate the relationship between the concentration of these cytokines, inflammatory cells and clinical features. RESULTS: 1) The concentration of TNF-alphain MEE from children younger than 2 years was significantly higher than the levels of children older than 2 years (p<0.05). 2) The concentration of TNF-alpha in MEE of preoperative medication group was significantly lower than the levels of non-medication group (p<0.05). 3) The concentration of IL-6 in MEE of the ears with hearing threshold poorer than 35 dB was significantly higher than the levels of the ears with hearing threshold better than 35 dB (p<0.05). CONCLUSION: The results showed that TNF-alpha and IL-6 are intimately involved in the inflammatory cascade of the middle ear and suggest regulation of these cytokines as possible sites of future therapeutic intervention in otitis media with effusion.

A Comparison of Clinical Outcomes between Decompressive Lumbar Laminectomy Alone and with Arthrodesis in Degenerative Lumbar Spinal Stenosis

To evaluate the relationship between surgical procedures and clinical outcomes in degenerative lumbar spinal stenosis, we retrospectively analyzed the results of the patients who had been performed decompressive lumbar spinal surgery. Eighty-five patients with degenerative lumbar spinal stenosis underwent decompressive lumbar spinal surgery between Jan. 1994 and Dec. 1996. The patients were randomly assigned to one of two groups; decompression alone(47 patients) and decompression with arthrodesis(38 patients). Among the patients with arthrodesis, the instruments were placed in 34 patients. The follow-up duration was 16-51 months(mean; 32.8 months). Functional outcome was excellent or good in 96% of the patients with decompression alone and in 97% of those with decompression with arthrodesis(p=0.667), and the overall patient's satisfaction was 87.5% and 89.5%, respectively. Although the various factors, which could be possible influent to the clinical outcome, were considered, there were no statistically significant differences in results between the two groups. The findings of this study demonstrate that the spinal fusion procedure has no benefit in clinical outcomes of the patients with degenerative lumbar spinal stenosis. Thus the fusion procedures with instrumentation should be used only in carefully selected patients because of its potential risks of serious complications, such as nerve root injury, massive bleeding, and infection.

Probable Primary Leptomeningeal Melanoma: A Case Report

Primary leptomeningeal melanomas(PLMs) are rare aggressive central nervous system(CNS) tumors without systemic foci. It can be very difficult, however, to clearly distinguish PLMs from those that have metastasized. We report a case of malignant leptomenigeal melanoma occurring in the right temporal convexity of a 77-yearold woman. Almost all malignant CNS melanomas in the old are secondary to the cutaneous melanoma and can cause diverse neurological manifestations; certain clinical findings of the presented case-namely, the patient's age, vague neurologic findings and absence of cutaneous lesions -are therefore interesting. Thorough clinical checkups, including whole-body bone scan, whole spine MRI, abdominal ultrasound, and tumor marker studies to find extracranial lesions revealed no abnormalities. Based on these clinical findings, we suppose-though are not certain-that the tumor of the presented case is a PLM.