A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis.

OBJECTIVE: Lorecivivint (LOR; SM04690), an investigational Wnt pathway modulator, previously demonstrated patient-reported and radiographic outcome improvements vs placebo in clinically relevant subjects with moderate to severe knee osteoarthritis (OA). This study's objective was to identify effective LOR doses. DESIGN: Subjects in this 24-week, Phase 2b, multicenter, randomized, double-blind, placebo (PBO)-controlled trial received an intra-articular injection of 2 mL LOR (0.03, 0.07, 0.15, or 0.23 mg), PBO, or dry-needle sham. The primary efficacy endpoints were changes in Pain NRS [0-10], WOMAC Pain [0-100], WOMAC Function [0-100], and radiographic mJSW outcomes, which were measured using baseline-adjusted analysis of covariance at Week 24. Multiple Comparison Procedure-Modeling (MCP-Mod) was performed for dose modeling. RESULTS: In total, 695/700 subjects were treated. Pain NRS showed significant improvements vs PBO after treatment with 0.07 mg and 0.23 mg LOR at Weeks 12 (-0.96, 95% CI [-1.54, -0.37], P = 0.001; -0.78 [-1.39, -0.17], P = 0.012) and 24 (-0.70 [-1.34, -0.06], P = 0.031; -0.82 [-1.51, -0.12], P = 0.022). Additionally, 0.07 mg LOR significantly improved WOMAC Pain and Function subscores vs PBO at Week 12 (P = 0.04, P = 0.021), and 0.23 mg LOR significantly improved both WOMAC subscores at Week 24 (P = 0.031, P = 0.017). No significant differences from PBO were observed for other doses. No radiographic progression was observed in any group at Week 24. MCP-Mod identified 0.07 mg LOR as the lowest effective dose. CONCLUSION: This 24-week Phase 2b trial demonstrated the efficacy of LOR on PROs in knee OA subjects. The optimal dose for future studies was identified as 0.07 mg LOR.

Predicting outgrowth of IgE-mediated cow's milk allergy: Diagnostic tests in children under two years of age.

BACKGROUND: Limited studies conducted on children <2 years old and/or involving a skin prick test (SPT) for fresh milk (FM) have examined the predictive value of allergometric tests for outgrowth of cow's milk allergy (CMA). We investigated the optimal decision points for outgrowth (ODPfo) with SPT for commercial cow's milk extract (CE) and FM and specific immunoglobulin E (sIgE) levels for milk proteins to predict outgrowing allergy in children <2 years old. METHODS: SPTs for CE and FM, tests for sIgEs (cow's milk, casein, α-lactoalbumin, ß-lactoglobulin) and oral food challenges (OFC) were performed in children referred for evaluation of suspected CMA, and 15 months after diagnosis. RESULTS: Fifty-one children (median age, 7.5 months; range, 2-23 months) were enrolled. Five had a history of anaphylaxis and 26 of 48 children with a positive initial challenge underwent milk elimination. The last OFC was performed in 28 children of whom 13 reacted to milk. The initial SPT responses to CE and FM and milk sIgE levels of the patients with persistent CMA were higher at diagnosis, with ODPfo of 7mm, 9mm, and 10.5kU/L, respectively; these values remained higher with ODPfo of 4mm, 11mm, and 10.5kU/L at the last OFC. CONCLUSION: Higher initial SPTs for FM and CE and higher initial sIgE levels for cow's milk proteins are associated with a reduced likelihood of outgrowth. Initial milk sIgE level <10.5kU/L and initial SPT for fresh milk <9mm are related to the acquisition of tolerance in the follow-up period.

Tolerance to baked and fermented cow's milk in children with IgE-mediated and non-IgE-mediated cow's milk allergy in patients under two years of age.

BACKGROUND: IgE-mediated cow's milk allergy (CMA) has been shown consistent in milder heated-milk tolerant and severe heated-milk reactant groups in patients older than two years. Little is known whether fermentation of milk gives rise to similar clinical phenotypes. We aimed to determine the influence of extensively heated and fermented cow's milk on the IgE-mediated and non-IgE-mediated CMA in children younger than two years. METHODS: Subjects followed with the diagnosis of IgE-mediated and non-IgE-mediated CMA for at least six months underwent unheated milk challenge. IgE-mediated and non-IgE-mediated groups were categorised as unheated milk-reactive and tolerant, separately. Unheated milk-reactive groups were further challenged sequentially with fermented milk (yoghurt) and baked milk, 15 days apart. Allergy evaluation with skin tests, prick-to-prick tests and atopy patch tests were performed. RESULTS: Fifty-seven children (median age: 14 months; range: 7-24 months) underwent unheated milk challenge. Eleven of 27 children with IgE-mediated CMA and 14 of 30 children with non-IgE-mediated CMA tolerated unheated milk. Among subjects who reacted to unheated milk; 15 of 16 subjects (93%) with IgE-mediated CMA also reacted to yoghurt, whereas 11 of 16 subjects (68%) with non-IgE-mediated CMA tolerated fermented milk. Thirteen subjects (81%) of the unheated milk-reactive IgE-mediated group tolerated to heated milk. None of 16 subjects of unheated milk-reactive non-IgE-mediated group reacted to baked milk. CONCLUSION: The majority of children under the age of two years with both IgE-mediated and non-IgE-mediated CMA tolerated baked-milk products. Yoghurt was tolerated in two thirds of unheated milk reactive patients suffering from non-IgE-mediated CMA.

Leakage testing for different adhesive systems and composites to permanent teeth.

AIM: To explore the microleakage of different adhesive systems and flowable composites to permanent teeth. SUBJECTS AND METHODS: In this study, a total of 84 human premolar teeth were used. Class V cavities were prepared on the buccal surfaces. The teeth were randomly assigned to six groups of 14 teeth each as follows: The first group - etch-rinse adhesive applied and cavities filled with flowable composite, the second group - etch-rinse adhesive applied and cavities filled with bulk-fill resin composite, the third group - one-stage self-etch (SE) adhesive applied and cavities filled with flowable composite, the fourth group - one-stage SE adhesive applied and cavities filled with bulk-fill resin composite, the fifth group - two-stage SE adhesive applied and cavities filled with flowable composite, and the sixth group - two-stage SE adhesive applied and cavities filled with bulk-fill resin composite. All specimens were then stored for 24 h at 37°C in distilled water. Teeth were then thermocycled for 500 cycles between 5°C and 55°C prior to immersion in 0.5% basic fuchsin for 24 h. Two mesiodistal cuts of each tooth were photographed for leakage with a digital camera. The dye infiltrated surface for each specimen was measured and data were collected with a software program. Statistical evaluations were done by nonparametric Kruskal-Wallis test and Mann-Whitney U-test. RESULTS: There were statistically significant differences in mean microleakage ratio among the groups (P < 0.05). The first group had shown significantly increased microleakage areas than the other four groups (third, fourth, fifth, and sixth groups) (P < 0.05), except for the second group (P > 0.05). It was also no significant different between the mean microleakage areas of group fourth and group fifth (P > 0.05). The sixth group had exhibited the lowest microleakage areas, and it was statistically significant (P < 0.05) compared to the other groups. CONCLUSION: In this study, it has been found that the use of total etch adhesive systems resulted in high leakage values.

Effect of Erbium:yttrium aluminum garnet laser on bond strength of a total-etch adhesive system to caries-affected dentin on gingival wall.

PURPOSE: To assess the effect of the erbium:yttrium aluminum garnet (Er:YAG) laser on bond strength of a total-etch adhesive system to the caries-affected dentin on the gingival wall. MATERIALS AND METHODS: Ten human molars with proximal carious lesions were randomly divided into two groups. In the first group, the carious dentin was removed with a bur, whereas in the second group it was removed with the Er:YAG laser. Carious lesions were excavated with one of these two techniques until laser fluorescence values decreased to 15 in the center of the lesions. The teeth were then restored with a total-etch adhesive system (Adper Single Bond 2) and composite resin (Filtek Z250). Five teeth from each group were sectioned to obtain 1 mm2 stick-shaped microtensile specimens from each tooth. Twenty-five specimens were obtained for each group with using this technique. The data were analyzed in independent-samples t-test (α = 0.05). For each removal technique, one sample was analyzed using scanning electron microscopy. RESULTS: No statistically significant differences were found between the bond strength of the Er:YAG laser and the bur-treated groups (P > 0.05). CONCLUSION: The Er:YAG laser treatment did not negatively affect the bonding performance of the total-etch adhesive system to caries-affected dentin on the gingival wall.

Pronounced interferon-alpha production from plasmacytoid dendritic cells in patients with Behçet's disease following CpG D ODN stimulation.

OBJECTIVE: Several lines of evidence point to a polarized T-helper-1 (Th1) immune response in Behçet's disease (BD). Interferon (IFN)-alpha which has an ability to promote strong Th1 type immune response has been shown to increase in patients with BD. In order to clarify if plasmacytoid dendritic cells (pDCs) abnormally respond to a stimulus in patients with BD, we investigated the levels of intracellular IFN-alpha and beta in pDCs with or without CpG D ODN stimulation. METHODS: The study population consisted of 8 patients with clinically active BD, 8 ankylosing spondilitis (AS) patients having active disease and 11 healthy volunteers. pDC subsets in peripheral blood mononuclear cells (PBMCs) cultures were analysed by flow cytometry. RESULTS: The percentage of IFN-alpha+ pDCs in unstimulated PBMCs cultures from patients BD was significantly higher (p=0.036) than in AS and HC. But this difference disappeared in stimulated PBMCs cultures (p=0.167). The mean fluorescence intensity (MFI) of IFN-alpha+ pDCs in stimulated PBMCs cultures of BD patients was significantly higher than those from patients with AS and HC. The percentage of IFN-beta+ pDCs in unstimulated PBMCs cultures from patients with BD and AS was significantly higher (p=0.004) than in HC. But this difference was not significant in stimulated PBMCs cultures (p=0.694). When compared to healthy subjects, the MFI of IFN-beta + pDCs in unstimulated and stimulated PBMCs cultures from patients with BD and AS was not different (p=0.287, p=0.152, respectively). In patients with BD, the percentage and MFI of IFN-alpha+ pDCs were higher (p=0.012 for all) in stimulated PBMCs cultures as compared to unstimulated ones. CONCLUSION: We suggest that increased frequency of IFN-alpha+ pDC in BD patients and the higher sensitiveness of these cells to CpG D ODN stimulus contribute to high serum IFN-alpha levels found in these patients which eventually resulted in Th1 type immune response.

Turkish version of impact on family scale: a study of reliability and validity.

BACKGROUND: Although there is a considerably high prevalence of developmental disorders in Turkey there are not many assessment tools related to evaluating the impact of these children on their family. The aim of this study was to determine the validity and reliability of the Turkish version of the Impact on Family Scale (IPFAM), a health related quality of life measurement to be utilized in clinical trials, health care services, research and evaluation. METHODS: Caregivers of 85 children with developmental disabilities answered the questionnaire and 65 of them answered it twice with a one week interval. The reliability of the measurement was assessed by Cronbach's alpha coefficient, and with intraclass correlation coefficient (ICC) for test-retest reliability. Construct validity was assessed by calculating the correlation between total impact score of IPFAM, WeeFIM and the physiotherapists' evaluation via Visual Analogue Scale (VAS) to determine the child's disability. RESULTS: Test-retest reliability was found to be ICC = 0.953 for total impact, 0.843 for financial support, 0.940 for general impact, 0.871 for disruption of social relations and 0.787 for coping. Internal consistency was tested using Cronbach's alpha and was found to be 0.902 for total impact of IPFAM. For construct validity the correlation between total impact score of IPFAM and WeeFIM was r = -0,532 (p < 0.001) and the correlation between total impact score of IPFAM and the physiotherapist's evaluation was r = 0.519 (p < 0.001). CONCLUSION: The Turkish version of IPFAM was found to be a reliable and valid instrument for assessing the impact of developmental disorders of the child on the family.

Synovial lymphoid neogenetic factors in Behçet's synovitis: do they play a role in self-limiting and subacute course of arthritis?

OBJECTIVE: Lymphoid neogenesis seems to play an important role in the persistence of chronic inflammation and has been shown in various disorders characterized by chronic inflammation including rheumatoid arthritis. Arthritis of Behçet's disease is characterized by non-erosive arthritis in which the disease course is considered to be subacute and self limiting. However, molecular mechanisms underlying those features of Behçet's arthritis have not been defined yet. In order to determine the contribution of lymphoid neogenesis in the disease course of Behçet's arthritis, we investigated the synovial fluid (SF) levels of CXCL 12, CXCL 13, CCL 21 homeostatic chemokines and the percentage of SF naive lymphocytes expressing their receptors such as CXCR4+ and CCR7+. We further measured the SF TGF-Beta and INF-Beta levels which are known to contribute lymphoid neogenesis via leading persistent expression of CXCR4 on T cells and inhibiting T cell apoptosis, respectively. METHODS: Fifty-one [15 BD, 17 RA, and 19 osteoarthritis (OA)] patients with at least one- sided knee arthritis were enrolled in the study. Patients with BD constituted the study group, and RA, OA patients were used as positive and negative control groups, respectively. The SF levels of CXCL 12, CXCL 13, CCL 21, TGF-Beta and INF-Beta were measured by ELISA. CXCR4, CCR7 chemokine receptors on SF lymphocytes were tested by Flow- cytometry. Kruskal-Wallis test and Mann-Whitney U test were used for statistical analysis where appropriate. RESULTS: Synovial fluid CCL 21 levels were found to be increased in RA patients as compared to BD and OA patients (p = 0.003, and p = 0.013, respectively). No significant difference was detected between BD and OA patients with respect to CCL 21 levels. Both CXCL 12 and CXCL 13 SF levels were found to be higher in RA and BD patients as compared to OA patients (CXCL-12; p = 0.012, and p = 0.024), (CXCL 13; p < 0.001, and p = 0.007). However, no difference with regard to SF levels of both CXCL 12 and CXCL 13 were found between RA and BD patients. Percentages of both CD3+CXCR4+ lymphocytes and CD3+CCR7+ lymphocytes in the SF of RA patients were detected to be increased as compared to those of BD and OA patients (CD3+CXCR4+; p = 0.019, p = 0.048, respectively), (CD3+CCR7+; p = 0.023, p = 0.001, respectively). However, no differences with respect to the percentages of SF lymphocytes expressing CD3+CXCR4+ or CD3+CCR7+ were found between BD and OA patients. Both TGF-Beta and INF-Beta SF levels were found to be higher in RA patients as compared to BD and OA patients (TGF-Beta; p = 0.041, and p = 0.003), (INF-Beta; p = 0.012, and p = 0.016). However, no differences with regard to SF levels of both TGF-Beta and INF-Beta were found between BD and OA patients. CONCLUSION: Considering the subacute, self limiting and non-erosive course of arthritis observed in BD, our finding of detection of lower levels of CCL21 and TGF-Beta1 and IFN-Beta in BD patients, seems to prevent the development of LN and chronic inflammation in Behçet's synovitis. In support of this view, percentages of SF naïve T lymphocytes were found to be lower in BD patients comparing with those of the RA. Absence of tertiary lymphoid structures in BD patients, may explain the spontaneous resolution of Behçet's arthritis in most of the cases.

Dendritic cell subsets and type I interferon system in Behçet's disease: does functional abnormality in plasmacytoid dendritic cells contribute to Th1 polarization?

OBJECTIVE: Several lines of evidence point to a polarized T-helper-1 (Th1) immune response in Behçet's disease (BD). However, it is not yet clear which factors are involved in the proposed Th1 mediated pathogenesis of BD. Dendritic cells (DCs) are antigen presenting cells which play a crucial role in the polarization of immune response. No previous study has examined the possible role of DCs in the pathogenesis of BD. We conducted both quantitative and functional analysis of the peripheral blood DC subsets in BD patients with different clinical presentations. METHODS: Thirty-eight patients with BD, 12 healthy controls (HC), and 12 patients with undifferentiated spondylarthritis (uSpA) were enrolled in the study. Peripheral blood DC subsets were analysed by flow cytometry and were further characterized for maturation with CCR7. Serum levels of interferon (IFN)-alpha and IFN-b were measured by ELISA. RESULTS: BD patients had a decreased percentage of plasmacytoid DCs (pDCs) compared to HC (p = 0.036). IFN-alpha levels were found to be increased in BD patients as compared to HC and uSPA (p < 0.001, p = 0.005, respectively). BD patients had decreased levels of IFN-Beta as compared to HC and uSpA (p = 0.013, p = 0.004, respectively). No difference was found between HC and patients with uSpA regarding IFN-Beta levels. Subgroup analysis of BD patients disclosed normalization of percentage of pDCs and the level of IFN-Beta in patients receiving IFN-alpha-2b. CONCLUSION: We suggest abnormalities in pDCs and type I IFNs appear to be a master switch leading to the pathogenicity in BD by directing immune response towards Th1.

Serum MMP-2 and MMP-9 in patients with Behçet's disease: do their higher levels correlate to vasculo-Behçet's disease associated with aneurysm formation?

OBJECTIVES: Basic and clinical studies have revealed a strong correlation between matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, and the formation of abdominal aortic aneurysms. In addition, previous studies have clearly shown that MMP-2 and MMP-9 play an important role in the pathogenesis of vasculitis characterized by aneurysm formation such as Kawasaki disease, temporal arteritis and Takayasu arteritis. Depending on those findings, we hypothesized that circulating MMP-2 and MMP-9 could be useful markers to demonstrate vascular aneurysmatic involvement in patients with Behçet's disease (BD). METHODS: Fifty-eight patients with BD, and 20 healthy controls were enrolled in the study. We assessed the disease activity of patients according to the Leeds activity score system. We compared the Leeds activity scores of patients with their serum levels of MMP2 and MMP-9. Patients with BD were categorized as active (total activity score > or = 5) or inactive (total activity score < 5). Patients were further categorized with respect to their extent of involvement as muco-cutaneous or systemic. Patients with systemic involvement were subdivided into ocular or vascular involvement. Patients with vascular involvement were subgrouped as thrombotic or aneurysmatic involvement. The levels of MMP-2 and MMP-9 were measured by ELISA. RESULTS: Serum MMP-9 but not MMP-2 levels were significantly higher both in patients with active and inactive disease as compared to healthy controls (p = 0.008 and 0.013 respectively). We found positive correlation between Leeds activity score and serum MMP-2 levels in patients with vascular involvement (p = 0.035 and r = 0.485), and serum MMP-9 levels in active BD patients (p = 0.003 and r = 0.599). The serum levels of MMP-2 and MMP-9 in patients with systemic involvement were higher than those of healthy controls but not patients with mucocutaneous involvement (p = 0.046 and 0.002 respectively). The serum levels of MMP-2 in patients with vascular involvement were found to be higher than those of healthy controls and patients with mucocutaneous involvement (p = 0.001 and 0.003, respectively) but not different in those with ocular involvement. The serum levels of MMP-9 in patients with vascular involvement were found to be higher than those of healthy controls and ocular disease (p = 0.001 and 0.033 respectively) but not different in those with mucocutaneous involvement. The serum levels of MMP-2 in patients with aneurysmatic involvement were found to be higher than those of healthy controls, mucocutaneous and ocular involvement (p = 0.004, 0.008 and 0.004 respectively). The serum levels of MMP-2 in patients with thrombotic involvement were found to be higher than those of healthy controls and mucocutaneous (p = 0.018 and 0.033 respectively) but not ocular involvement. The serum levels of MMP-9 in patients with aneurysmatic involvement were found to be higher than those of healthy controls, mucocutaneous and ocular involvement (p = 0.001, 0.048 and 0.007 respectively). The serum levels of MMP-9 in patients with thrombotic involvement were found to be higher than those of healthy controls but not mucocutaneous and ocular involvement (p = 0.046). CONCLUSIONS: We concluded that serum MMP-2 and MMP-9 levels can be used as an activity indicator for vasculo-Behçet's or active Behçet's patients, respectively. But they can not be used as a marker reflecting the systemic involvement of patients with BD. The systemic expressions of MMP-2 and MMP-9 were strongly associated with vasculo-Behçet's disease, particularly aneurysmatic involvement, suggesting their pathogenetic roles in vasculo-Behçet's disease complicated with aneurysm formation.

Assessment of sexual functions in patients with chronic liver disease.

We aimed to determine the sexual problems and the prevalence of erectile dysfunction (ED) in patients with chronic liver disease by means of International Index of Erectile Function (IIEF). A total of 81 patients with stable chronic liver disease were included in the study. Patients were grouped as mild to moderate (Child Pugh A and B) (n=10), chronic hepatitis (hepatitis B, C and D) (n=28) and carriers (n=43) according to the type of their chronic liver disease. All patients were asked to complete a questionnaire including IIEF and demographics. The IIEF domain scores were calculated and ED grading was determined on erectile function domain. IIEF domain scores were compared between these groups. The mean age was 54.8 +/- 10.8 y. Using the IIEF, the prevalence of any ED was 50.6% for all patients, and 50, 50, and 51.1% for cirrhosis, chronic hepatitis and carriers, respectively. The IIEF domain scores were not significantly different among the patient groups. Sexual functions did not appear to be affected by the stable chronic liver disease.

Vascular endothelial growth factor and monocyte chemoattractant protein-1 in Behçet's patients with venous thrombosis.

OBJECTIVE: Vascular lesions can involve both arterial and venous systems which are often the major causes complicating the disease course of Behçet's disease (BD). Vascular endothelial growth factor (VEGF) is a stimulant of angiogenesis secondary to ischemia while monocyte chemoattractant protein 1 (MCP-1) is induced by shear stresses leading to vascular collateral development. MCP-1 has been also shown to contribute to the recanalization of venous thrombi. Tumor necrosis factor-alpha (TNF-alpha) is known to play a major role in the pathogenesis of BD. Furthermore, up-regulation of secreted MCP-1 and VEGF was observed following stimulation with TNF-alpha. In view of the above functions of VEGF, MCP-1 and TNF-alpha, we hypothesized that these factors may be important in the pathogenesis of thrombosis seen in BD. METHODS: A total of 36 patients with a diagnosis of BD were studied. BD patients were separated into 3 groups with respect to vascular involvement. Group BD-AT (n = 9) with acute thrombosis, BD-CT (n = 12) with chronic thrombosis and BD-MC (n = 15) with mucocutaneous involvement only. The control group (group H) was comprised of 20 healthy persons. In addition, patients with acute, DC-AT (n= 11) and patients with chronic DC-CT (n = 9) thrombosis without BD served as disease controls. Serum measurements of VEGF MCP-1 and TNF-alpha were performed by quantitative sandwich ELISA. The acute phase reactants, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured. RESULTS: The levels of VEGF were significantly higher in the patients in group BD-AT than either in group BD-CT or BD-MC (p = 0.03 and p < 0.001, respectively). However, no significant difference was found for VEGF levels of thrombotic patients regarding the cause (BD-AT vs. DC-AT, p = 0.063; BD-CT vs. DC-CT, p = 0.084) or the stage of thrombosis (DC-AT vs. DC-CT, p > 0.05). Both BD patients and disease controls with acute thrombosis had significantly higher levels of MCP-1 as compared to corresponding chronic thrombosis patients (BD-AT vs. DC-CT; p < 0.001; DC-AT vs. DC-CT, p < 0.001). Patients with BD and disease controls had significantly higher serum TNF-alpha level when compared with healthy subjects. No significant difference with respect to serum TNF-alpha level was noted when patient subgroups with BD and disease controls were compared with each other Serum levels of VEGF, MCP-1, and TNF-alpha were not found to be correlated with either ESR or CRP (p > 0.05). CONCLUSIONS: Increased levels of VEGF and MCP-1 detected in BD thrombosis suggest the possible role of those angiogenic cytokines in the pathogenesis. Although not specific for BD, detection of VEGF or MCP-1 levels seems to serve as an assay for differentiation of BD patients with acute thrombosis from chronic.

The proportional Venn diagram of Behçet's disease-related manifestations among young adult men in Turkey.

OBJECTIVES: To determine the frequency of the features associated with Behçet's disease (BD) in a young men population and generate a proportional Venn diagram of those features. METHODS: Data was collected from 3714 otherwise healthy men recruited for military service at the entrance. Study was conducted in a two-step procedure. Firstly, all participants were questioned by a general practitioner via using visual Behçet's questionnaire. Those participants, in whom at least one BD-related manifestation of the disease (oral ulcer, genital ulcer, folliculitis, erythema nodosum, uveitis, venous involvement of the lower extremities) have been demonstrated, were further examined by a rheumatologist at the second-stage of the study. RESULTS: The areas of intersection among the 6 individual BD-related manifestations produced 63 mutually exclusive symptom groups. Sixteen out 63 of these groups were functionally operative in our study population. Forty-seven (1.2%) of the all participants were considered to have at least 1 of the BD-related manifestation after examined by rheumatologist. The prevalence rates of the individual manifestations among the study population were as follows; oral ulcer 29 (0.78%), folliculitis 31 (0.83%), genital ulcer 9 (0.24%), venous involvement 13 (0.35%), erythema nodosum 4 (0.10%) and uveitis 3 (0.08%). The group consisting of oral ulcer with folliculitis was the largest proportion of participants followed by the group having oral ulcer only, accounting for 0.29% and 0.18%, respectively. Four (0.1%) of the participants were fulfilled the International Study Group for BD criteria following rheumatologic and ophthalmologic examinations. After excluding the group having oral ulcer with folliculitis, additional 12 cases had features suggesting BD though they didn't fulfill the International Study Group for BD criteria. CONCLUSION: The Venn diagram of this study demonstrates that International Study Group for BD criteria can detect almost the quarter of 16 cases suspected as having BD. We suggest that the application of information regarding the frequencies of individual BD-related manifestations and their association with each other in a general population might serve as a helpful tool for physicians while making diagnosis.

Inhibition of inducible nitric oxide synthase reduces bacterial translocation in a rat model of acute pancreatitis.

INTRODUCTION: Translocation of bacteria from the gut into pancreatic necrosis is an important factor in the development of septic complications and mortality in acute pancreatitis. S-methylisothiourea (SMT) is an inducible nitric oxide synthase inhibitor that has been shown to decrease bacteria] translocation in sepsis and thermal injury. AIM: To investigate whether SMT could affect bacterial translocation in acute necrotizing pancreatitis. METHODOLOGY: Forty-five Sprague-Dawley rats were studied. Acute pancreatitis was induced in Group I and Group II by injection of taurocholate and trypsin into the common biliopancreatic duct. Group III underwent laparotomy with the manipulation (but not cannulation) of the pancreas and received saline injection. Group I rats received normal saline as a placebo, and Group II rats received SMT after surgery for 2 days. At 48 hours, blood was drawn for serum amylase determinations. Bacterial translocation to mesenteric lymph nodes and distant sites (pancreas, liver, and peritoneum) were examined. A point scoring system of histologic features was used to evaluate the severity of pancreatitis. RESULTS: Plasma amylase levels and pancreatic histologic score were significantly reduced in Group II rats given SMT compared with those in Group I rats given saline (p < 0.01, p < 0.05, respectively). All Group I rats had bacterial translocation to mesenteric lymph nodes compared with 7 of 12 rats in Group II (p < 0.05). There was no difference in bacterial translocation to distant organs between the two groups, although rates tended to be lower in Group II compared with Group I (p > 0.05). Bacterial counts in the pancreas were significantly reduced in Group II rats compared with those in Group I rats (p < 0.05). CONCLUSION: Treatment with SMT appears to have ameliorated the course of acute pancreatitis; however, mortality was not affected.

Fulminant hepatic failure as the initial manifestation of primary hepatocellular carcinoma.

A 20-year-old male, with no history of chronic liver disease, presented with fulminant hepatic failure. The cause was not established until post mortem when it was found that he had a primary hepatocellular carcinoma in a non-cirrhotic liver. To our knowledge, this is the third report of hepatocellular carcinoma presenting in this manner. Although rare, primary malignancies of the liver should be considered in the differential diagnosis of fulminant hepatic failure, especially when other more common causes are excluded.