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Increase of Plasma IL-12/p40 Ratio Induced by the Combined Therapy of DNA Vaccine and Lamivudine Correlates with Sustained Viremia Control in CHB Carriers

  • Im, Se-Jin;Yang, Se-Hwan;Yoon, Seung-Kew;Sung, Young-Chul
    • IMMUNE NETWORK
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    • v.9 no.1
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    • pp.20-26
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    • 2009
  • We previously reported that $IFN-{\gamma}$ producing T cell responses induced by the combined therapy of DNA vaccine and lamivudine for one year are important for the induction of sustained virological response (SVR). However, $IFN-{\gamma}$ production is not sufficient to predict sustained viremia control in chronic hepatitis B (CHB) carriers treated. Methods: Twelve CHB carriers were intramuscularly immunized 12 times at a 4-week interval with 8mg of HBV DNA vaccine during the standard lamivudine treatment (100mg/daily/1 year). The level of cytokines during and after the combined therapy in plasma of all 12 CHB carriers treated was determined by each ELISA kit. Six out of 12 CHB carriers revisited the clinic, and their HBV DNA levels were examined. Results: The combined therapy increased plasma IL-12 and IL-12/p40 ratio during the treatment (baseline vs. peak level: $41.8{\pm}8.3$ vs. $163.1{\pm}29.2\;pg/ml$; p<0.01 and $0.96{\pm}0.25$ vs. $3.58{\pm}0.86$; p<0.01, respectively), and the peak level of plasma IL-12 and IL-12/p40 ratio was evoked at 6 to 10 months during the combined therapy. In particular, CHB carriers with SVR had two and three-fold higher level of the peak plasma IL-12 and plasma IL-12/p40 ratio than non-virological responders (NVRs), respectively ($218.0{\pm}41.4$ vs. $108.1{\pm}28.6\;pg/ml$; p=0.09 and $5.35{\pm}1.38$ vs. $1.80{\pm}0.29$; p<0.05, respectively), while p40 level was consistent during the combined therapy. In addition, there was no significant temporal correlation between the peak IL-12/p40 ratio and the elevation of serum alanine amino-transferase (ALT) in this study, contrast to $IFN-{\alpha}$ therapy which induced peak IL-12 level following ALT flares. Conclusion: Our results indicate that the combined therapy induces the increase of plasma IL-12 and IL-12/p40 ratio, which are associated with long-term SVR in CHB carriers.

AN EXPERIMENTAL STUDY ON THE OSSEOINTEGRATION OF THE TI-6AL-4V BEAD COATING IMPLANTS (Ti-6Al-4V 비드코팅 임프란트 시제품의 골유착에 대한 실험적 연구)

  • Woo, Jin-Oh;Park, Bong-Wook;Byun, June-Ho;Kim, Seung-Eon;Kim, Gyoo-Cheon;Park, Bong-Soo;Kim, Jong-Ryoul
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.30 no.1
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    • pp.52-59
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    • 2008
  • The geometric design of an implant surface may play an important role in affecting early osseointegration. It is well known that the porous surfaced implant had much benefits for the osseointegration and the early stability of implant. However, the porous surfaced implant had weakness from the transgingival contamitants, and it resulted in alveolar bone loss. The other problem identified with porous surface implant is the loss of physical properties resulting from the bead sintering process. In this study, we developed the new bead coating implant to overcome the disadvantages of porous surfaced implant. Ti-6Al-4V beads were supplied from STARMET (USA). The beads were prepared by a plasma rotating electrode process (PREP) and had a nearly spherical shape with a diameter of 75-150 ${\mu}m$. Two types of titanium implants were supplied by KJ Meditech (Korea). One is an external hexa system (External type) and the other is an internal system with threads (Internal type). The implants were pasted with beads using polyvinylalcohol solution as a binder, and then sintered at 1250 $^{\circ}C$ for 2 hours in vacuum of $10^{-5}$ torr. The resulting porous structure was 400-500 ${\mu}m$ thick and consisted of three to four bead layers bonded to each other and the implant. The pore size was in the range of 50-150 ${\mu}m$ and the porosity was 30-40 % in volume. The aim of this study was to evaluate the osseointegration of the newly developed dental implant. The experimental implants (n=16) were inserted in the unilateral femur of 4 mongrel dogs. All animals were killed at 8 weeks after implantation, and samples were harvested for hitological examination. All bead coated porous implants were successfully osseointegrated with peripheral bone. The average bone-implant contact ratios were 84.6 % (External type) and 81.5 % (Internal type). In the modified Goldner's trichrome staining, new generated mature bones were observed at the implant interface at 8 weeks after implantation. Although, further studies are required, we could conclude that the newly developed vacuum sintered Ti-6Al-4V bead coating implant was strong enough to resist the implant insertion force, and it was easily osseointegrated with peripheral bone.

A Study on the Effect of Herbal-acupuncture with Phellodendri Cortex Solution on Collagen-induced Arthritis in DBA/1J Mice (황백약침이 콜라겐 유도 관절염 생쥐에 미치는 영향)

  • Kim, Jae-Young;Lee, Hyun
    • Korean Journal of Acupuncture
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    • v.24 no.2
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    • pp.163-184
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    • 2007
  • Objectives & Methods : The purpose of this study is to observe the effects of Phellodendri Cortex Herbal-acupuncture solution (PC-HAS) at Joksamni (ST36) on collagen II induced arthritis in DBA-1J mice. The author performed several experimental items to analyze arthritis evaluation, change of weight, spleen size and adhesion rate, change of cytokine level, IgG, IgM and anti-collagen II, chang of immunocyte count, histological change of CIA mouse joint. Results : 1. In the PC-HA group, arthritis index, the incidence of arthritis and joint edema were significantly decreased. 2. In the PC-HA group, the change of spleen size, spleen adhesion rate and the knee joint were significantly decreased. 3. The levels of $IL-1{\beta}$, IL-6 and INF- in serum of the CIA mouse were significantly decreased by PC-HA. 4. The levels of IgG, IgM and anti-collagen II in serum of the CIA mouse were significantly decreased by PC-HA. 5. In the CIA mouse spleen cell culture, the levels of IFN- , IFN- / IL-4, IL-10 were significantly decreased by PC-HA, but the level of IL-4 was significantly increased by PC-HA. 6. In the PC-HA group, the ratios of $CD3e^+$ to $CD45R^+$ cell, $CD4^+$ to $CD8^+$ cell and $CD4^+/CD25^+$ cell were similarly maintained as normal group in the CIA mouse spleen cell. 7. In the PC-HA group, $CD4^+CD25^+$ and $CD45R^+/CD69^+$ cell were significantly decreased in the lymph nodes. 8. In the PC-HA group, $CD3^+/CD69^+$ and $CD11b^+/Gr-1^+$ cell were significantly decreased in knee joint. 9. In histology, the cartilage destruction and synovial cell proliferation in the PC-HA group were similar with that of the normal group and the collagen fiber expressions in the PC-HA group were similar with that of the normal group. Conclusions : Form the result above, the results suggest that the PC-HA at ST36 has significant effect on collagen-induced arthritis, and can be put to practical use in the future rheumatoid arthritis clinic.

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Influence of review system using computerized program for Acute Respiratory Infection upon practicing doctors' behaviour (전산프로그램을 이용한 급성호흡기감염증 청구자료 심사 시행 후 개원의의 진료 및 청구 행태 변화)

  • Chung Seol-Hee;Park Eun-Chul;Jeong Hyoung-Sun
    • Health Policy and Management
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    • v.16 no.2
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    • pp.49-76
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    • 2006
  • The aim of this study was to explore the effects of a computerized review program which was introduced in August 1, 2003, using claims data for acute respiratory infection related diseases. National Health Insurance (NHI) claims data on respiratory infection related diseases before and after the introduction, with six month intervals respectively, were used for the analysis. Clinic was the unit of observation, and clinics with only one physician whose specialty was internal medicine, pediatrics, otorhinolaryngology and family medicine and clinics with a general practitioner were selected. The final sample had 7,637 clinics in total. Indices used to measure practice pattern was prescription rates of antibiotics, prescription rates of injection drug per visit, treatment costs per claim, and total costs per claim. Changes in the number of claims for major disease categories and upcoding index for disease categories were used to measure claiming behavior. Data were analysed using descriptive analysis, t-test for indices changes before and after the introduction, analysis of variance (ANOVA) for practice pattern change for major disease categories, and multiple regression analysis to identify whether new system influenced on provider' practice patterns or not. Prescription of antibiotics, prescription rates of injection drug, treatment costs per claim, and total costs per claim decreased significantly. Results from multiple regression analysis showed that a computerized review system had effects on all the indices measuring behavior. Introduction of the new system had the spillover effects on the provider's behavior in the related disease categories in addition to the effects in the target diseases, but the magnitude of the effects were bigger among the target diseases. Rates of claims for computerized review over total claims for respiratory diseases significantly decreased after the introduction of a computerized review system and rates of claims for non target diseases increased, which was also statistically significant. Distribution of the number of claims by disease categories after the introduction of a computerized review system changed so as to increase the costs per claims. Analysis of upcoding index showed index for 'other acute lower respiratory infection (J20-22)', which was included in the review target, decreased and 'otitis media (H65, H66)', which was not included in the review target, increase. Factors affecting provider's practice patterns should be taken into consideration when policies on claims review method and behavior changes. It is critical to include strategies to decrease the variations among providers.

Effect of Water Extract of Peonia Suffruticosa and Prunus Percica on Anti-inflammation (목단피((牧丹皮).도인(桃仁) 배합(配合)이 항염증(抗炎症) 작용(作用)에 미치는 영향)

  • Kim, Young-Il;Lee, Sung-Jun;Huh, Jin;Lee, Tae-Hyung;Shin, Dong-Gean;Lee, Jae-Cheol;Shin, Yong-Seo;Yun, Young-Gab
    • Herbal Formula Science
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    • v.18 no.1
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    • pp.105-120
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    • 2010
  • Paeonia Suffruticosa and Prunus Persica have been used as oriental medicine for removal of fever, alleviation of pain, an anti-phlogistic effect and removal of extravasated blood. However, it has been never shown the effects of these herbal medicines on anti-inflammatory processes. This experiment was performed to show how these herbs could act as anti-inflammatory medicines at cellular level. Anti-inflammation effects of water extracts from Paeonia Suffruticosa and Prunus Persica as well as their mixture have been investigated, and the results were follows; 1) each extract slightly suppressed the expression and production of inflammatory mediators and enzymes such as NO, iNOS, IL-$1{\beta}$, and TNF-$\alpha$ in lipopolysaccharid(LPS)-stimulated RAW264.7 cells and mouse primary peritoneal macrophages in a dose-dependent manner. These suppressive effects, however, were synergistically increased by their mixture. 2) Each extract of Paeonia Suffruticosa and Prunus Persica insignificantly suppressed the activation and activity of NF-${\kappa}B$ in LPS-stimulated RAW264.7 cells, which controls the expression of inflammatory mediators such as NO, iNOS, IL-$1{\beta}$, and TNF-$\alpha$. However, extract mixture of Paeonia Suffruticosa and Prunus Persica suppressed effectively the activation and activity of NF-${\kappa}B$. 3) Each of Paeonia Suffruticosa and Prunus Persica induced translocation of NF-${\kappa}B$ to the nucleus from the cytosol and DNA-binding activity of nuclear NF-${\kappa}B$ in LPS-activated RAW264.7 cells. The extract mixture of Paeonia Suffruticosa and Prunus Persica showed more significant suppression of the NF-${\kappa}B$ translocation and its DNA-binding activity, as compared to those of the each extract. These results suggest that the extract mixture of Paeonia Suffruticosa and Prunus Persica may affect different control mechanisms for NF-${\kappa}B$ activation and the expression and production of NF-${\kappa}B$-dependent inflammatory mediators, indicating that this extract mixture may be useful for treatment of inflammatory diseases.

Misuse of testosterone replacement therapy in men in infertile couples and its influence on infertility treatment

  • Song, Seung-Hun;Sung, Suye;Her, Young Sun;Oh, Mihee;Shin, Dong Hyuk;Lee, Jinil;Baek, Jeongwon;Lee, Woo Sik;Kim, Dong Suk
    • Clinical and Experimental Reproductive Medicine
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    • v.46 no.4
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    • pp.173-177
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    • 2019
  • Objective: We investigated the clinical characteristics of men with testosterone replacement therapy (TRT)-induced hypogonadism and its effect on assisted reproductive technology (ART) in infertile couples. Methods: This study examined the records of 20 consecutive male patients diagnosed with azoospermia or severe oligozoospermia (< 5 × 106/mL) who visited a single infertility center from January 2008 to July 2018. All patients were treated at a primary clinic for erectile dysfunction or androgen deficiency symptoms combined with low serum testosterone. All men received a phosphodiesterase 5 inhibitor and TRT with testosterone undecanoate (Nebido®) or testosterone enanthate (Jenasteron®). Patients older than 50 years or with a chronic medical disease such as diabetes were excluded. Results: The mean age of patients was 37 years and the mean duration of infertility was 16.3 ± 11.6 months. At the initial presentation, eight patients had azoospermia, nine had cryptozoospermia, and three had severe oligozoospermia. Serum follicle-stimulating hormone levels were below 1.0 mIU/mL in most patients. Three ongoing ART programs with female factor infertility were cancelled due to male spermatogenic dysfunction; two of these men had normal semen parameters in the previous cycle. After withholding TRT, serum hormone levels and sperm concentrations returned to normal range after a median duration of 8 months. Conclusion: TRT with high-dose testosterone can cause spermatogenic dysfunction due to suppression of the hypothalamic-pituitary-testicular axis, with adverse effects on infertility treatment programs. TRT is therefore contraindicated for infertile couples attempting to conceive, and the patient's desire for fertility must be considered before initiation of TRT in a hypogonadal man.

External Fixation of Retaining Ligament in Correction of Facial Disfigurement in Type-1 Neurofibromatosis Patients (유지 인대의 외부 고정을 통한 제1형 신경섬유종증 환자의 안면부 변형 교정)

  • Myung, Yu-Jin;Lee, Yoon-Ho
    • Archives of Plastic Surgery
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    • v.38 no.3
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    • pp.257-262
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    • 2011
  • Purpose: In neurofibromatosis patients, complete surgical excision of the mass is almost impossible and surgical treatment usually consists of multiple serial excisions that only result in a debulking effect. Remnant tumor mass has a gravitational effect on facial soft tissues that leads to sagging of skin and soft tissue, and eventually, facial disfigurement and asymmetry. The purpose of our surgical method is to perform soft tissue lifting with longer lasting effect with less surgical risk of damaging facial nerve and vessels. With external fixation using K-wire or surgical screw, the procedure only called for a short incision length and had additional adhesive properties that enabled anchoring of soft tissue in a lifted position for a longer postoperative period. Methods: A total of 5 neurofibromatosis patients (NF-1) visited our clinic for mass reduction and face lifting. The age of patients ranged from 13 to 42 (mean 28.8 years), and most patients had a long history of multiple excisions in the past. Face lifting was performed in 2 different areas, the periorbital area in 3 patients, and the midface in 2 patients. The materials used in fixation of retaining ligament were K-wire (n=3) and titanium screw (n=2). Results: Follow up period was from 5 month to 3 years and 1 month (mean=2 years and 1 month). All patients conveyed satisfaction with the results and no major complications were reported. The lifting effect lasted for as long as 3 years, and there were no complaints of relapse of soft tissue depression or sagging within the operated area. 1 patient (M/13) needed secondary k-wire insertion and additional mass excision in 1 year and 10 months postoperatively due to tumor growth. In two patients with K-wire fixation, mild dimpling and tenderness were observed in the follow up period, but in about 2 months postoperatively, dimpling was relieved and there was no need for removal of fixating material. Conclusion: Surgical lifting in neurofibromatosis patients can be challenging, for mass excision cannot be done completely and gravitational effect by residual mass can be persistent. External fixation of the retaining ligament in patients with neurofibromatosis can give satisfactory results-for incision length is relatively shorter, and the lifting effect can last longer compared to other various face lifting techniques.

The Reactivity to 2TU PPD Tuberculin Skin Test after Percutaneous Multiple Puncture BCG Vaccination (건강한 영아에서 경피다자법 BCG 접종후 2TU 투베르쿨린 검사의 반응성)

  • Roh, Hye Ok;Lee, Woo Gill
    • Pediatric Infection and Vaccine
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    • v.6 no.1
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    • pp.101-106
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    • 1999
  • Purpose : Tuberculosis, a major public health problem, is an important cause of childhood infectious diseases. To decrease the tuberculosis morbidity rate, BCG vaccination and chemoprophylaxis are performed. Recently 2TU PPD skin test was introduced as a diagnostic method for tuberculous infection. We studied the positive conversion rate of 2TU PPD test after percutaneous multiple puncture BCG vaccination. Methods : Four hundred seventy six infants from well baby clinic of Samsung Cheil Hospital were enrolled. They were immunized with percutaneous multiple puncture technique BCG(Japan BCG laboratory, Japan) at 1 month of age. Approximately 6 months later, tuberculin skin test using RT23 2TU PPD was performed. Induration size, family history of tuberculosis and number of BCG scars were evaluated. Induration greater than or equal to 5mm was defined as positive conversion. Results : Among 476 infants, 248(52.1%) were male and 228(47.9%) were female. PPD skin tests were performed $6.2{\pm}0.5$($mean{\pm}S.D.$) months after BCG vaccination. Mean induration size was $7.3{\pm}3.2mm$ and positive conversion rate was 85.5%. Total number of BCG scars was $15.5{\pm}3.2$. Conclusion : The seroconversion rate by 2TU PPD test after percutaneous multiple puncture BCG vaccination was high. But, more comparative studies with various age groups may be needed for 2TU PPD test used as diagnostic method of tuberculosis in the hospitals.

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A STUDY ON THE INFLUENCE OF EPINEPHRINE CONTAINED IN DENTAL LOCAL ANESTHETIC AGENTS ON THE BLOOD SUGAR OF DIABETES DURING MINOR ORAL SURGERY (치과용 국소마취제에 포함된 Epinephrine이 당뇨 환자의 소수술시 혈당에 미치는 영향에 관한 연구)

  • Yun, Hyung-Jin;Rim, Jae-Suk
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.27 no.5
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    • pp.463-471
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    • 2005
  • Recently, the number of diabetic patients have been increased with westernized living way and meal habitation. The regulation of blood sugar concentration is very important for diabetic patients to keep homeostasis and, to prevent acute or chronic complications. Epinephrine combined with lidocaine is used in dental clinic extensively. And epinephrine combined with lidocaine also effects on decreasing the blood leakage volume by constricting micro vessle and arteriole. But, So far there are few researches about the effect of epinephrine contained in dental local anesthetic agent on the blood sugar of diabetes during minor oral surgery. The purpose of this study was intended to investigate whether epinephrine which combined with dental local anesthetics influence body glucose level in diabetes patients by glucose monitoring. The subject of this study were 38 diabetic patients and 38 normal adults, each patient was checked body glucose after a meal 2 hours later with resting state, and injection 1:100000 epinephrine with dental lidocaine 54 ml or lidocaine 54 ml only. And then the body glucose level was checked 5 minutes and 30 minutes after injection. The results were analyzed by two way ANOVA test (p<0.05). The results were as follows: In the experimental group 1, the mean of the blood sugar level was 180.3 mg/dl before an anesthetic injection, 182.8 mg/dl after 5minutes of the anesthetic injection and 182.2 mg/dl after 30minutes of the anesthetic injection. The change of the blood sugar level was not statistically by two-way ANOVA tests (p<0.05). In the experimental group 2, the mean of the blood sugar level was 237 mg/dl before an anesthetic injection, 234.5 mg/dl after 5minutes of the anesthetic injection and 231.8 mg/dl after 30minutes of the anesthetic injection. The change of the blood sugar level was not statistically by two-way ANOVA tests (p<0.05). In the controlled group 1, the mean of the blood sugar level was 117.6 mg/dl before an anesthetic injection, 119.1 mg/dl after 5minutes of the anesthetic injection and 129.3 mg/dl after 30minutes of the anesthetic injection. The change of the blood sugar level was not statistically by two-way ANOVA tests (p<0.05). In the controlled group 2, the mean of the blood sugar level was 104.2 mg/dl before an anesthetic injection, 102 mg/dl after 5minutes of the anesthetic injection and 105.3 mg/dl after 30minutes of the anesthetic injection. The change of the blood sugar level was not statistically by two-way ANOVA tests (p<0.05).

A Study on the Effects of Local Factors on the Oral Ulcers Observed in Behcet s Disease (베체트 병의 구강궤양에 대한 국소인자의 영향에 관한 연구)

  • Myoung-Chan Kim;Chong-Youl Kim
    • Journal of Oral Medicine and Pain
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    • v.17 no.2
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    • pp.75-86
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    • 1992
  • Of the many first-occuring major manifestations of Behcet's disease, the oral ulcer is most frequently observed, shows the highest mean recurrence rate, and the longest mean duration period. A study of the relationship between mechanical irritation buy local factors and the recurrence of oral ulcers was carried out to see if there is a correlation. The subjects chosen for the study were 81 patients who were referred to the Department of Oral Diagnosis at Yonsei University Dental Hospital from the Behcet clinic of Severace Hospital after being diagnosed as Behcet's disease patients. 1. By Shimuzu's classification, possible type was the most numerous with 55.55% ; while suspected type was 19.76% ; incomplete type, 17,28% ; and complete type, 7.41% were observed in that order. The male to female ration was 1 to 1.61, and the average age of onset was 17.63 years. 2. Oral ulcers developed most frequently on the tongue (48.28%), and lip(23.15%), buccal mucosa (20.69%), palate\pharynx(4.43%), and gingiva(3.45%) also showed ulceration. 3. 38.27% of the patients were HSV positive : 27.16% were CRP positive ; 12.34% were ASO positive ; 9.87% were RF positive ; and 3.7% were ANA positive. 4. According to the answers to the survey, fatigue(85.18%) was most frequently associated with Behcet's diseage. Trauma by tooth brushing (22.22%), un specified reasons (20.98%), hard food chewing (12.35%), and irritation by dentition and/or prosthesis (13.58%) were observed in association with Behcet's disease. 23.46% had a history of tonsilitis. 5. Oral ulcers on the anterior part of tongue and buccal mucosa were associated with local irritatants. 6. Oral ulcers on the lip and posterior portion of tongue were not associated with local irritants. Local irritation by dentition and oral ulcer on the anterior part of tongue and buccal mucosa was observed to coexit with one another : in other words, lo9cal factors can act to cause of recurrence of an oral ulcer and to delay the healing process in Behcet's disease. Therefore, elimination of local factors along with systemic therapy must be recommended when treating oral ulcers.

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