18 FTHK-5351 PET Patterns in Patients With Alzheimer’s Disease and Negative Amyloid PET Findings

Background@#and Purpose Alzheimer’s disease (AD) does not always mean amyloid positivity. [ 18 F]THK-5351 has been shown to be able to detect reactive astrogliosis as well as tau accompanied by neurodegenerative changes. We evaluated the [ 18 F]THK-5351 retention patterns in positron-emission tomography (PET) and the clinical characteristics of patients clinically diagnosed with AD dementia who had negative amyloid PET findings. @*Methods@#We performed 3.0-T magnetic resonance imaging, [ 18 F]THK-5351 PET, and amyloid PET in 164 patients with AD dementia. Amyloid PET was visually scored as positive or negative. [ 18 F]THK-5351 PET were visually classified as having an intratemporal or extratemporal spread pattern. @*Results@#The 164 patients included 23 (14.0%) who were amyloid-negative (age 74.9±8.3 years, mean±standard deviation; 9 males, 14 females). Amyloid-negative patients were older, had a higher prevalence of diabetes mellitus, and had better visuospatial and memory functions. The frequency of the apolipoprotein E ε4 allele was higher and the hippocampal volume was smaller in amyloid-positive patients. [ 18 F]THK-5351 uptake patterns of the amyloid-negative patients were classified into intratemporal spread (n=10) and extratemporal spread (n=13).Neuropsychological test results did not differ significantly between these two groups. The standardized uptake value ratio of [ 18 F]THK-5351 was higher in the extratemporal spread group (2.01±0.26 vs. 1.61±0.15, p=0.001). After 1 year, Mini Mental State Examination (MMSE) scores decreased significantly in the extratemporal spread group (-3.5±3.2, p=0.006) but not in the intratemporal spread group (-0.5±2.8, p=0.916). The diagnosis remained as AD (n=5, 50%) or changed to other diagnoses (n=5, 50%) in the intratemporal group, whereas it remained as AD (n=8, 61.5%) or changed to frontotemporal dementia (n=4, 30.8%) and other diagnoses (n=1, 7.7%) in the extratemporal spread group. @*Conclusions@#Approximately 70% of the patients with amyloid-negative AD showed abnormal [ 18 F]THK-5351 retention. MMSE scores deteriorated rapidly in the patients with an extratemporal spread pattern.

Effects of taurine and ginseng extracts on energy metabolism during exercise and their anti-fatigue properties in mice

BACKGROUND/OBJECTIVES@#Ginseng extract (GSE) and taurine (TR) are widely used antifatigue resources in functional foods. However, the mechanism underlying the antifatigue effects of GSE and TR are still unclear. Hence, we investigated whether GSE and TR have synergistic effects against fatigue in mice.MATERIALS/METHODS: L6 cells were treated with different concentrations of TR and GSE, and cell viability was determined using 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium. Oxidative stress was analyzed by immunocytochemistry using MitoTracker™ Red FM and an anti-8-oxoguanine antibody. Respiratory gas analysis was performed to investigate metabolism. Expression of an activated protein kinase was analyzed using immunohistochemistry. Gene expression of cluster of differentiation 36 and pyruvate dehydrogenase lipoamide kinase isozyme 4 was measured using reverse transcription– polymerase chain reaction. Mice were orally administered TR, GSE, or their combination for 30 days, and then fatigue-related parameters, including lactate, blood urea nitrogen, and glycogen, were measured after forced swimming. @*RESULTS@#TR and GSE reduced oxidative stress levels in hydrogen peroxide-stimulated L6 cells and enhanced the oxygen uptake and lipid metabolism in mice after acute exercise. After oral administration of TR or GSE for 30 days, the fatigue-related parameters did not change in mice. However, the mice administered GSE (400 mg/kg/day) alone for 30 days could swim longer than those from the other groups. Further, no synergistic effect was observed after the swimming exercise in mice treated with the TR and GSE combination for 30 days. @*CONCLUSIONS@#Taken together, our data suggest that TR and GSE may exert antifatigue effects in mice after acute exercise by enhancing oxygen uptake and lipid oxidation.

18F-THK5351 PET Positivity and Longitudinal Changes in Cognitive Function in β-Amyloid-Negative Amnestic Mild Cognitive Impairment

Purpose@#Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer’s disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ–) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer’s disease pathophysiology. Accordingly, we investigated associations between 18F-THK5351 PET positivity and cognitive decline among Aβ– aMCI patients. @*Materials and Methods@#The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: 18F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18F-THK5351 PET positivity on cognitive prognosis among Aβ– aMCI patients. @*Results@#Among the 25 Aβ– aMCI patients, 10 (40.0%) were 18F-THK5351 positive. The patients in the 18F-THK5351-positive group were older than those in the 18F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p<0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the 18F-THK5351-positive group deteriorated at a faster rate than those of the 18F-THK5351-negative group (B=0.003, p=0.033). @*Conclusion@#The results of the present study suggest that increased 18F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ– aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).

Longitudinal Decline of Striatal Subregional ¹⁸FFP-CIT Uptake in Parkinson's Disease / 대한핵의학회잡지

PURPOSE: Dopamine transporter imaging is suggested to be a useful imaging biomarker for Parkinson's disease (PD) progression and monitoring drug effects.We investigated the longitudinal decline characteristics of striatal [¹⁸F]FP-CIT uptake in PD.METHODS: We retrospectively reviewed 35 PD patients and 9 non-PD patients. All patients underwent [¹⁸F]FP-CIT PET at the initial diagnosis and follow-up. PET images were spatially normalized and analyzed with eight striatal and one occipital VOI templates. We measured the specific to non-specific binding ratio (SNBR) of the striatal subregions and calculated the absolute annual reduction (AAR) and relative annual reduction (%RAR) of the SNBRs.RESULTS: Total striatal SNBRs in PD patients were significantly lower than those in non-PD patients, with the most significant difference in the posterior putamen. Both AAR (0.26 ± 0.14 vs. 0.09 ± 0.19, p < 0.05) and %RAR (6.9 ± 3.5 vs. 1.2 ± 2.7, p < 0.001) of total striatal SNBRs were significantly greater in PD than non-PD patients. There were no significant differences in the AAR and %RAR of total striatal SNBRs between elderly and young onset PD. The AARs of the posterior putamen were higher in early PD than in advanced PD. Conversely, the %RARs were not significantly different between early and more advanced PD. The disease duration was significantly negatively correlated with the AAR but not with the %RAR of the posterior putamen.CONCLUSIONS: The longitudinal decline of striatal [¹⁸F]FP-CIT uptake in PD was nonlinear and significantly faster than that in non-PD, with a different rate of decline among the striatal subregions.

Molecular Imaging in Neurodegenerative Diseases

Neurodegenerative diseases are highly morbid and widespread in the nation with aged population. Since these are progressive and irreversible diseases, early detection and differentiation of the disease are important for possible therapeutic intervention. Alzheimer's disease and Parkinson's disease are the most frequent and costly devastating neurodegenerative diseases. Recent advances of molecular imaging, especially positron emission tomography (PET) technique, allows non-invasive evaluation of not only regional cerebral metabolism or perfusion, but also the change of neurotransmission and presence of abnormal protein such as beta amyloid. In Parkinsonism, dopamine transporter and vesicular monoamine transporter imaging are useful in the diagnosis and evaluation of the disease progression since these provide information about the integrity of presynaptic striatal dopaminergic neurons. In Alzheimer s disease, beta-amyloid imaging can assess the amyloid deposition. It improves early diagnosis and possibility of a presymptomatic diagnostic biomarker; improves understanding of the natural history of amyloid deposition; and has the capability to directly measure the effects of newly developed anti-amyloid therapies. Cholinergic and microglial imaging can be also useful in the early diagnosis of dementia and improves understanding of insights into pathophysiology of neurodegenerative diseases. Therefore, the ability of molecular imaging to identify and quantify cerebral pathology has significant implications for early detection, differential diagnosis, and therapeutic monitoring in neurodegenerative diseases.

Molecular Imaging in Neurodegenerative Diseases

Neurodegenerative diseases are highly morbid and widespread in the nation with aged population. Since these are progressive and irreversible diseases, early detection and differentiation of the disease are important for possible therapeutic intervention. Alzheimer's disease and Parkinson's disease are the most frequent and costly devastating neurodegenerative diseases. Recent advances of molecular imaging, especially positron emission tomography (PET) technique, allows non-invasive evaluation of not only regional cerebral metabolism or perfusion, but also the change of neurotransmission and presence of abnormal protein such as beta amyloid. In Parkinsonism, dopamine transporter and vesicular monoamine transporter imaging are useful in the diagnosis and evaluation of the disease progression since these provide information about the integrity of presynaptic striatal dopaminergic neurons. In Alzheimer s disease, beta-amyloid imaging can assess the amyloid deposition. It improves early diagnosis and possibility of a presymptomatic diagnostic biomarker; improves understanding of the natural history of amyloid deposition; and has the capability to directly measure the effects of newly developed anti-amyloid therapies. Cholinergic and microglial imaging can be also useful in the early diagnosis of dementia and improves understanding of insights into pathophysiology of neurodegenerative diseases. Therefore, the ability of molecular imaging to identify and quantify cerebral pathology has significant implications for early detection, differential diagnosis, and therapeutic monitoring in neurodegenerative diseases.

Pilot Study for the Prediction of Response to Radiotherapy Using (18)FFluorothymidine PET in Nasopharyngeal Cancer: Comparison with (18)FFDG PET / 핵의학분자영상

PURPOSE: This study was performed to know whether [(18)F]Fluorothymidine (FLT) positron emission tomography (PET) can be used to monitor early response to radiotherapy in comparison with [(18)F]Fluorodeoxyglucose (FDG) PET, and to establish the optimal imaging time for prediction of therapy response. MATERIALS AND METHODS: Two patients with nasopharyngeal cancer underwent serial FLT PET and FDG PET before and during radiotherapy. Three on-treatment FLT and FDG PET scans were performed on 1 week, 2 weeks and 3 weeks (at each time of 10 Gy, 20 Gy and 30 Gy delivered). The peak standardized uptake values (SUV(peak)) of primary tumors were measured on FLT and FDG PET. Then, percent changes of SUV(peak) after therapy were calculated. RESULTS: In two patients, baseline values of SUV(peak) on FDT PET were higher than those on FLT PET (FLT vs FDG; 3.7 vs 5.0, and 5.7 vs 15.0). In patient 1, FLT SUV(peak) showed 78%, 78% and 84% of decrease on 1 week, 2 and 3 weeks after treatment, whereas FDG SUV(peak) showed 18%, 52% and 66% of decrease, respectively. In patient 2, FLT SUV(peak) showed 75%, 75% and 68% of decrease, whereas FDG SUV(peak) showed 51%, 49% and 58% of decrease, respectively. Both patients reached to complete remission after radiotherapy. CONCLUSION: After radiotherapy, the decrease of FLT tumor uptake preceded the decrease of FDG tumor uptake in patients with nasopharyngeal cancer, and 1 week after therapy may be appropriate time for the assessment of early response. FLT PET might be more useful than FDG PET for monitoring early response to radiotherapy.

A Pilot Study for the Feasibility of F-18 FLT-PET in Locally Advanced Breast Cancer: Comparison with F-18 FDG-PET / 핵의학분자영상

PURPOSE: The aim of this study was to investigate the feasibility of 3'-[F-18]fluoro-3'-deoxythymidine positron emission tomography(FLT-PET) for the detection of locally advanced breast cancer and to compare the degree of FLT and 2'-deoxy-2'-[F-18]fluoro-d-glucose(FDG) uptake in primary tumor, lymph nodes and other normal organs. MATERIAL AND METHODS: The study subjects consisted of 22 female patients (mean age; 42+/-6 years) with biopsy-confirmed infiltrating ductal carcinoma between Aug 2005 and Nov 2006. We perfomed conventional imaging workup, FDG-PET and FLT PET/CT. Average tumor size measured by MRI was 7.2+/-3.4 cm. With visual analysis, Tumor and Lymph node uptakes of FLT and FDG were determined by calculation of standardized uptake value (SUV) and tumor to background (TB) ratio. We compared FLT tumor uptake with FDG tumor uptake. We also investigated the correlation between FLT tumor uptake and FDG tumor uptake and the concordant rate with lymph node uptakes of FLT and FDG. FLT and FDG uptakes of bone marrow and liver were measured to compare the biodistribution of each other. RESULTS: All tumor lesions were visually detected in both FLT-PET and FDG-PET. There was no significant correlation between maximal tumor size by MRI and SUVmax of FLT-PET or FDG-PET (p>0.05). SUVmax and SUV75 (average SUV within volume of interest using 75% isocontour) of FLT-PET were significantly lower than those of FDG-PET in primary tumor (SUVmax; 6.3+/-5.2 vs 8.3+/-4.9, p=0.02 / SUV75; 5.3+/-4.3 vs 6.9+/-4.2, p=0.02). There is significant moderate correlation between uptake of FLT and FDG in primary tumor (SUVmax; rho=0.450, p=0.04 / SUV75; rho=0.472, p=0.03). But, TB ratio of FLT-PET was higher than that of FDG-PET(11.7+/-7.7 vs 6.3+/-3.8, p=0.001). The concordant rate between FLT and FDG uptake of lymph node was reasonably good (33/34). The FLT SUVs of liver and bone marrow were 4.2+/-1.2 and 8.3+/-4.9. The FDG SUVs of liver and bone marrow were 1.8+/-0.4 and 1.6+/-0.4. CONCLUSION: The uptakes of FLT were lower than those of FDG, but all patients of this study revealed good FLT uptakes of tumor and lymph node. Because FLT-PET revealed high TB ratio and concordant rate with lymph node uptakes of FDG-PET, FLT-PET could be a useful diagnostic tool in locally advanced breast cancer. But, physiological uptake and individual variation of FLT in bone marrow and liver will limit the diagnosis of bone and liver metastases.

Radiopharmaceuticals for Neurotransmitter Imaging / 핵의학분자영상

Neurotransmitter imaging with radiopharmaceuticals plays major role for understanding of neurological and psychiatric disorders such as Parkinson's disease and depression. Radiopharmaceuticals for neurotransmitter imaging can be divided to dopamine transporter imaging radiopharmaceuticals and serotonin trnasporter imaging radiopharmaceuticals. Many kinds of new dopamine transporter imaging radiopharmcaeuticals has a tropane ring and they showed different biological properties according to the substituted functional group on tropane ring. After the first clinical trials with [123I]beta-CIT, alkyl chain substituent introduced to tropane ring amine to decrease time for imaging acquisition and to increase selectivity. From these results, [123I]PE2I, [18F]FE-CNT, [123I]FP-CIT and [18F]FP-CIT were developed and they showed high uptake on the dopamine transporter rich regions and fast peak uptake equilibrium time within 4 hours after injection. [11C]McN 5652 was developed for serotonin trnasporter imaging but this compound showed slow kinetics and high background radioactivity. To overcome these problems, new diarylsulfide backbone derivatives such as ADAM, ODAM, AFM, and DASB were developed. In these candidates, [11C]AFM and [11C]DASB showed high binding affinity to serotonin transporter and fast in vivo kinetics. This paper gives an overview of current status on dopamine and serotonin transporter imaging radiopharmaceuitcals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.

New Trend of tumor PET imaging radiopharmaceuticals / 한양의대학술지

Tumor PET imaging with radiopharmaceuticals plays a major role in the understanding of tumor biological information and for diagnosis of tumorswith non-invasive methods. These radiopharmaceuticals can be divided into two categories radiopharmaceuticals for metabolic process imaging and for specific receptor imaging. Most tumor imaging radiopharmaceuticals such as [18F]FDG, [18F]FLT, and [11C]choline can be trapped in tumor cells by specific metabolic processes of each radiopharmaceutical and show an increase in metabolism of tumor regions. Unlike these compounds, the hypoxia imaging adiopharmaceuticals such as [18F]FMISO and [64Cu]ATSM are trapped by oxidative metabolic mechanisms under only hypoxic conditions of tumor cells. For tumor specific receptor imaging, [18F]FES for estrogen receptor positive breast cancer may be used and recent clinical results showed the possibility of evaluating tumor therapy responseby estrogen receptor imaging with [18F]FES. This paper gives an overview of the current status of tumor PET imaging adiopharmaceuticals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.

Effects of Enterotoxins of Staphylococcus Aureus on Ciliary Activity of the Nasal Mucosa / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The pathogenesis of paranasal sinusitis has not been fully understood. The role of staphylococcal enterotoxins in the development of the paranasal sinusitis has recently been identified. The aim of the study is to investigate the in vitro effects of enterotoxin of Staphylococcus aureus on ciliary activity of the nasal mucosa and its in vivo activity on histology of sinus mucosa. MATERIALS AND METHOD: Maxillary sinus mucosa of the rabbit is harvested and prepared. Ciliary beat frequency (CBF) of the mucosa is observed in the culture media containing staphylococcal enterotoxin A (SEA). After direct instillation of SEA into the maxillary sinus, CBF and the histological finding of the maxillary sinus mucosa are examined. RESULTS: After exposure to low dose enterotoxin (0.03 or 0.3 ng/ml of SEA), CBF did not decrease. But, after exposure to high dose enterotoxin (1.5, 3, 30 ng/ml of SEA), CBF decreased significantly as a function of time. Twenty four hours after instillation of high dose (30 ng/ml) SEA, CBF decreased. Seven days after instillation of high dose SEA, sinusitis is observed. After instillation of low dose (0.3 ng/ml) SEA, CBF and epithelial integrity is not affected. But, subepithelial edema and the infiltration of inflammatory cells are observed. CONCLUSION: The induction of sinusitis with high dose SEA may be related to the ciliostatic effect of staphylococcal enterotoxin. But, low dose staphylococcal enterotoxin can induce sinus inflammation without ciliostatic effect.

A Case of 45,X Turner's Syndrome with Iron Deficiency Anemia due to Menometrorrhagia and Spontaneous Sexual Development / 대한내분비학회지

Short stature and gonadal dysgenesis are two characteristic clinical features of Turners syndrome. Very rarely, patients with Turners syndrome may menstruate and even be fertile. We experienced a case of Turners syndrome with spontaneous sexual development and menstruation. A 16-year-old girl was referred for severe anemia and menometrorrahgia. She had nearly normal features, with the exception of a short stature and a single right kidney. Also, she had spontaneous development of secondary sexual characteristics. We performed and anemia study and evaluated her short stature. In chromosomal study of her bone marrow and peripheral blood lymphocytes, she was revealed to have monosomy 45,X. Herein, this case is reported, with a brief review of literature

Long-Term Outcomes after Treatment of Diffuse In-Stent Restenosis with Rotational Atherectomy Followed by Beta-Radiation Therapy with a 188Re-MAG3-Filled Balloon

BACKGROUND AND OBJECTIVES: Intracoronary radiation therapy for in-stent restenosis has been demonstrated to reduce restenosis and major adverse cardiac events. However, the long-term angiographic and clinical outcomes after beta radiation therapy have not been sufficiently evaluated. SUBJECTS AND METHODS: The long-term angiographic and clinical outcomes of 50 consecutive patients who had received beta-radiation therapy with an 188Re-MAG3-filled balloon after rotational atherectomy for diffuse in-stent restenosis (lesion length>10 mm) in native coronary arteries were evaluated. The radiation dose was 15 Gy at a depth of 1.0 mm into the vessel wall. RESULTS: The mean lesion length was 25.6+/-12.7 mm. Radiation was delivered successfully to all patients, without any procedural or in-hospital complications. At the 6-month angiogram, the restenosis rate was 10% (5/50). There were no major adverse cardiac events (MACE), such as death, myocardial infarction or target lesion revascularization (TLR), by the 6-month follow-up. Long-term clinical data were obtained from all patients during 30.1+/-4.5 months of follow-up. No myocardial infarction and one noncardiac death occurred during follow-up. A two-year follow-up angiogram was performed in 26 (58%) of 45 patients that showed a patent radiation segment at the 6-month angiogram. Significant narrowing of the diameter stenosis greater than 50% occurred in 6 (23%) of 26 patients between 6- and 24-months after the beta-radiation. Late TLR was performed in 6 patients. The rate of 30-month death-free survival and MACE-free survival were 98.0+/-2.0 and 86.9+/-5.0%, respectively. CONCLUSION: Beta-radiation using an 188Re-MAG3-filled balloon after rotational atherectomy is associated with favorable long-term angiographic and clinical outcomes.

Late Intravascular Ultrasound Findings of Patients Treated with Brachytherapy for Diffuse In-Stent Restenosis

BACKGROUND AND OBJECTIVE: The long-term effects of beta-irradiation on intimal hyperplasia (IH) within the stented segment and vessel, and the lumen dimensions of non-stented adjacent segments, have not been sufficiently evaluated in patients with ISR. The long-term (24 months) effects of beta-irradiation ((188)Re-MAG3-filled balloon) were evaluated using intravascular ultrasound (IVUS) in patients with in-stent restenosis (ISR). SUCJECTS AND METHODS: A two-year follow-up IVUS was performed in 30 patients with patent ISR segments at the 6-monthly follow-up angiography. Serial IVUS images were acquired at 5 equidistant intra-stent sites and 3 different reference segment sites (1, 2 and 4 mm from stent margin). RESULTS: The mean intra-stent IH area and IH burden significantly increased between 6 and 24 months-from 2.1+/-1.1 to 2.6+/-1.4 mm2 (p<0.001) and from 26+/-10 to 33+/-14% (p<0.001), respectively. There were significant decreases in the mean external elastic membrane (from 10.1+/-3.9 to 9.7+/-3.9 mm2, p=0.015) and lumen area (from 5.6+/-2.3 to 5.1+/-2.3mm2, p=0.021) within the distal reference segments between 6 and 24 months. Target lesion revascularization (TLR) was performed between 6 and 24 months in 6 patients (20%) following the beta-irradiation therapy. There were no significant differences between the TLR and non-TLR groups, with the exception of a smaller minimum lumen CSA at 24 months in the TLR group. CONCLUSION: Because of a small amount of late loss between 6 and 24 months, most irradiated ISR vessel segments remained stable for up to 2 years. However, quantitative evidence of late catch-up was evident in most patients and was significantly associated with 24-month TLR in some patients with a smaller minimum lumen area.

Transseptal Transsphenoidal Pituitary Surgery in Children: Influence on Nasal Symptoms and Growth of the External Nose / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Transseptal transsphenoidal approach (TSTS) to pituitary neoplasms has been accepted as a safe and relatively atraumatic means of removing pituitary tumors. This study was performed to analyze the efficacy of TSTS and its influences on nasal symptoms and external nasal deformities in pediatric patients. MATERIALS AND METHOD: Medical records of 18 patients under the age of 15 years, and who underwent TSTS between 1985 and 2001, were reviewed retrospectively. To analyze long-term results, all 18 patients were interviewed in a standardized telephone survey. RESULTS: The most common presenting symptom was visual disturbance (56%) followed by headache (44%). Revision operations were needed in 5 (28%) patients. There were no significant complications such as intractable epistaxis, recurrent sinusitis, anosmia or external nasal deformity. The most common surgical complication was nasal obstruction (17%). CONCLUSION: TSTS is an effective means of removing pituitary neoplasms in pediatric patients and does not produce severe adverse effects on the nasal function and cosmesis.

The Effects of Celecoxib on Wound Healing in Murine Wound Models / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Celecoxib has suppressive effects on the growth, angiogenesis, metastasis of solid tumors including head and neck squamous cell carcinoma. Recent report suggests that celecoxib can also be usefully applied for preventing tumor recurrence in the postoperative conditions with possible residual tumors. The aim of this study is to investigate the effects of celecoxib on the post-surgical wound healing and the systems including the gastro-intestinal (GI) tracts. MATERIALS AND METHOD: Incisional and excisional wound models were created in the C3H mice and celecoxib was administered at a dose of 20 mg/kg/day to the wounded mice. Photographic documentation of the wounds was performed every week. The mice were serially sacrificed 3, 7, 14, and 28 days after wounding. The re-epithelialization and capillary number of the wounded skin were measured and the side effects of celecoxib were observed. RESULTS: Re-epithelialization was suppressed by celecoxib only in the early phase at the day 10 of wounding, which was all recovered in the late phase at day 14. The capillary number of the wounded bed was not affected by the celecoxib treatment. In addition, celecoxib had no significant side effects on the body weight change and the GI tracts of the wounded mice. CONCLUSION: This murine wound models suggest that celecoxib is a safe drug with no significant side effects to treat late wound healing or the GI tracts.

The Effects of Ostium Reopening and Stress on the Recovery of Maxillary Mucosal Lesion in Rabbits with Maxillary Sinusitis / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: There have been many studies concerning histologic changes and effectiveness of specific treatment in the experimentally induced sinusitis model, but there are few studies about natural course of paranasal sinusitis. This study aimed to analyze the natural course of sinusitis and the influence of stress on the natural disease course. MATERIALS AND METHOD: Natural ostia of 120 rabbits were occluded and reopened at 10 days after occlusion. Rabbits were divided into six groups according to duration from reopening to sacrifice. Each group was sacrificed at 1, 4, 8, 12, 19, 26 days after reopening of the natural ostium. Each group was divided into a control and stress subgroups. Radiologic, gross and histologic findings were analyzed. RESULTS: Percentage of rabbits showing partial or total haziness was highest at 3 days after reopening in the control subgroup and at 11 days in the stress subgroup. Percentage of the rabbits showing moderate or severe amount of pus in the sinus on gross examination was highest at 4 days in both subgroups. Degree of epithelial loss was most severe at 4 days in both subgroups. Subepithelial thickness was largest and inflammatory cell infiltrations were most severe at 8 days in both subgroups. Although there was a lack of statistical significance, stress subgroups showed more severe gross, radiologic, and histologic findings than those of control subgroups. CONCLUSION: This study shows that maxillary sinusitis is induced by natural ostium occlusion only and is improved with time without any treatment, and that stress might influence the severity of maxillary sinusitis.

Application of Endoscopic Surgery on Sinonasal and Nasopharyngeal Malignancy / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Since the first introduction of nasal endoscope, its use has been widened from chronic sinusitis to a variety of diseases ; endoscopic management for tumors of sinonasal cavity and nasopharynx has increased these days as well. In the present study, we reviewed the treatment results of endoscopically managed sinonasal and nasopharyngeal malignant tumors. SUBJECTS AND METHOD: Medical records of six patients with sinonasal or nasopharyngeal malignant tumor who were treated using endoscopic technique were retrospectively reviewed. Patients' ages at diagnosis ranged from 23 to 74 years. RESULTS: In five patients, endoscopic approach was the sole approach technique used. In one patient, the Caldwell-Luc approach together with the endoscopic approach was used because the whole mass couldn't be removed using the endoscopic approach only. Five patients remained disease free. In one patient, the disease recurred at 24 months after treatment, which was also successfully removed with the endoscopic approach. CONCLUSION: In properly selected cases, endoscopic management in sinonasal and nasopharyngeal malignancy can be justified with the following advantages: it showed no aesthetic problems and there were less functional loss compared to the traditional open approach.

Papillary Cystadenocarcinoma Arising from Minor Salivary Glands in the Retromolar Trigone / 대한이비인후과학회지

Papillary cystadenocarcinoma is a very rare malignant neoplasm of the salivary gland. We report a case of papillary cystadenocarcinoma arising from the minor salivary gland in the retromolar trigone of a 56-year-old female patient presenting intermittent hemorrhage from the oral cavity. We discuss the clinical and histopathological features of the papillary cystadenocarcinoma of the salivary gland with the review of the literature.

Cerebrospinal Fluid Rhinorrhea-Clinical Manifestations and Endoscopic Repair / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Endoscopic technique in intranasal repair of cerebrospinal fluid (CSF) leakage has many advantages over external approaches. This study aimed to review the clinical manifestations of CSF leakage and to investigate the efficacy of the endoscope in the diagnosis and the management of CSF leakage. SUBJECTS AND METHOD: Twenty-four cases of CSF rhinorrhea were reviewed retrospectively. RESULTS: Seven out of 22 patients had only rhinorrhea and 14 cases had meningitis. Four cases were successfully managed with conservative management including bed rest and lumbar drains. Intranasal repairs with endoscopes have been applied to 17 cases out of 20 operated cases including 1 case in which both endoscopic repair and craniotomy was used. Endoscopic repairs were not useful in 3 cases in which the operative exposures were insufficient and the leakage sites could not be accessible with endoscope. One case was treated with a craniotomy approach, and in-dwelling shunt operations were required in 2 cases. Leak sites were repaired with free grafts using buccal fat, nasal mucosa, or temporalis muscle and fascia. In some cases, especially when the defect was large, we incorporated bone or cartilage into the grafts. There was no recurrence after the endoscopic closure. CONCLUSION: Endoscopic approach is safe and effective in managing the CSF rhinorrhea except in cases in which the operative exposure with endoscope is insufficient.