Association between multiple sclerosis and chronic periodontitis: a population-based pilot study.

BACKGROUND AND PURPOSE: The pathogenesis of multiple sclerosis (MS) is still not fully understood, but multiple infections are known to be crucial in the development of the disease. Periodontitis caused by periodontopathic polymicrobial infections is among the most common chronic infectious disorders. This case-control study aimed to investigate the association between chronic periodontitis (CP) and MS using a population-based dataset in Taiwan. METHODS: This study included 316 cases who had a diagnosis of MS and 1580 randomly selected controls. We performed conditional logistic regressions to investigate the association between MS and having been previously diagnosed with CP. RESULTS: The results reveal that the prevalence of earlier CP was 25.6% and 15.4% for cases and controls, respectively (P < 0.001). Conditional logistic regression analysis revealed that cases were 1.86 [95% confidence interval (CI) = 1.39-2.48] times as likely as controls to have been previously diagnosed with CP, after adjusting for sociodemographic characteristics as well as hyperlipidemia, hypertension, coronary heart disease, alcohol abuse/alcohol-dependence syndrome, tobacco use disorder and chronic obstructive pulmonary disease. After analyzing by gender, it was realized that while female cases had a higher chance than female controls of having earlier CP (adjusted odds ratio = 2.08; 95% CI = 1.49-2.95), there was no statistical association detected between these two conditions in men. CONCLUSIONS: This study provides evidence for an association between CP and MS in female, but not male, subjects. Further epidemiological studies are needed to confirm the association and gender-specific differences found in the present study.

Association analysis of dopaminergic gene variants (Comt, Drd4 And Dat1) with Alzheimer s disease.

Defects in dopaminergic transmission play important roles in the disturbance of synaptic plasticity and even in advanced cognitive behavior. However, the relationship between genes involved in the regulation of dopamine levels and predisposition for Alzheimer s disease (AD) remains unclear. The potential association of dopamine-modulating gene polymorphisms with AD was evaluated. We performed a case-control study with 120 patients and 86 healthy controls. Two catechol-O-methyltransferase (COMT) single-nucleotide polymorphisms (SNPs) (rs2020917 and rs4646312), two dopamine D4 receptor (DRD4) SNPs (rs3758653 and rs916455), and four dopamine transporter (DAT1) SNPs (rs2937639, rs6347, rs12516948 and rs11133762) were investigated. The T allele at the DRD4 SNP (rs3758653) was found to be significantly associated with AD. Our results also showed that haplotype frequencies, observed from the analyzed SNPs, were distributed significantly differently in AD patients vs control subjects. Moreover, a strong association was observed between the A allele at rs6347 of DAT1 and moderate stage of dementia. These observations suggest that genetic variations in the dopamine-modulating genes, COMT, DRD4 and DAT1, may contribute to AD pathogenesis in the Taiwanese population.

Clinical characteristics and treatment delay of cerebral infarction in tuberculous meningitis.

BACKGROUND: Cerebral infarction (CI) complicating tuberculous meningitis (TBM) is a major risk factor of permanent disability. The prevention of this complication is an important issue in the quality care of TBM patients. AIM: Our aim was to evaluate the clinical characteristics of TBM patients with CI. METHODS: Ninety-one adult patients with TBM were studied between 1999 and 2007. Clinical, neuroradiological and cerebrospinal fluid data of patients with CI were compared with those without CI. RESULTS: Thirty of the 91 patients had CI, including symptomatic CI occurring before admission in 10 patients, symptomatic CI occurring during hospitalisation in four and silent CI in 16 patients. When compared with non-CI patients, patients with CI were younger and associated with focal weakness on presentation, and had basal meningeal enhancement and hydrocephalus on brain images. Prolonged doctor delays of antituberculosis and steroid therapies, neurosurgical intervention, focal weakness and dementia as sequelae, and poor outcomes were associated with patients with CI than non-CI patients. CONCLUSION: Contrast-enhanced brain imaging is helpful to explore the basal meningeal enhancement in CI patients, and contributes to early diagnosis and treatment of TBM. Early antituberculosis and steroid therapies may help prevent CI in TBM patients.

IL-10 and TNF-alpha promoter polymorphisms in susceptibility to systemic lupus erythematosus in Taiwan.

OBJECTIVES: The genetic control of Interleukin-10 (IL-10) and Tumour necrosis factor-alpha (TNF-alpha) production and the possible interaction between the two cytokines in influencing SLE susceptibility as well as clinical features has not been completely evaluated in the Taiwanese population. METHODS: We investigated the association of IL-10 and TNF-alpha promoter polymorphisms (-1082, -819 and -592 for IL-10 gene; -308 for TNF-alpha gene) with SLE in a total of 172 Taiwanese patients and 215 controls. RESULTS: Our results indicate that IL-10 A/T/A-A/T/A genotype was associated with Taiwanese SLE, whereas no significance was observed between TNF-alpha genotype and SLE. Furthermore, the TNF-alpha G allele frequency of the polymorphism at -308 was significantly decreased in patients with oral ulcers. The combined frequencies of IL-10 A/T/A haplotype and TNF-alpha G-G genotype were significantly increased in SLE patients. In addition, the combined frequencies of IL-10 A/T/A haplotype and TNF-alpha G-G genotype were significantly decreased in patients with oral ulcers. CONCLUSIONS: These results suggest a significant correlation of the combined IL-10 and TNF-alpha genetic polymorphisms contribute to SLE susceptibility and clinical features in the Taiwanese population.

Association of COL11A2 polymorphism with susceptibility to Kawasaki disease and development of coronary artery lesions.

Kawasaki disease (KD) is a pediatric systemic vasculitis of unknown etiology wherein genetic influence is suspected. Gene clusters within the HLA region at chromosome 6p21.3 have been linked to KD and other autoimmune disorders. As collagen is a strong autoantigen inducing chronic inflammation in patients with vasculitis, this study tests a hypothesis that single-nucleotide polymorphism (SNP) of a collagen gene, COL11A2, located in this HLA region may affect susceptibility to Kawasaki disease and its arterial sequels. SNP sites rs2294478 (at promoter) and rs2076311 (at intron 19) were genome-typed on 93 KD patients and 680 healthy subjects. Genotypic and allelic frequencies analyses found A allele at rs2076311 as a risk allele for KD. Clinical association study showed protective potential of C/C genotype at rs2294478 and A/A at rs2076311 for developing coronary artery lesions (CALs) in patients. In addition, C-A haplotype of COL11A2 gene associates with KD development and can serve as a genetic marker to differentiate KD patients lacking CALs from those with such lesions. Our findings suggest the involvement of genetic variations of COL11A2 in Kawasaki disease and CAL formation.

Single nucleotide polymorphism rs2229634 in the ITPR3 gene is associated with the risk of developing coronary artery aneurysm in children with Kawasaki disease.

Kawasaki disease (KD) is the most common form of pediatric vasculitis. Though its etiology is unknown, researchers have suggested that it is related to genetics. The inositol 1,4,5-triphosphate receptor type 3 (ITPR3) gene has a strong association with the development of type 1 diabetes and, plays a critical role in the development of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Graves' disease. The aim of study is to examine the association of ITPR3 polymorphisms with KD risk in Taiwanese children. This study evaluates the single nucleotide polymorphisms (SNP) rs2229634 in the ITPR3 gene with KD in a case-control study involving 93 KD patients and 680 healthy, gender- and age-matched controls. The frequency of the rs2229634 T/T genotype was significantly higher in KD patients with coronary artery aneurysm (CAA) than in patients without CAA [odds ratio (OR) = 2.56, 95% confidence interval (95% CI) = 1.35-4.88, P = 0.004]. In addition, KD patients with the T/T genotype elevated mean serum levels of C-reactive protein compared with patients with the C/C or C/T genotype (12.2 mg dL(-1) vs. 8.5 mg dL(-1) , P = 0.036). In conclusion, the results of this study suggest that the rs2229634 SNP in the ITPR3 gene is associated with the risk of CAA formation in Taiwanese KD patients.

Complications impaired endothelial progenitor cell function in Type 2 diabetic patients with or without critical leg ischaemia: implication for impaired neovascularization in diabetes.

AIMS: This study tested the hypothesis that migratory function of endothelial progenitor cells (EPCs) is impaired in Type 2 diabetic patients with or without critical leg ischaemia. METHODS: Seventy-four patients were classified into four groups: Type 2 diabetic (n = 21) and non-diabetic patients (n = 10) with critical leg ischaemia and Type 2 diabetic patients without lower extremity vascular disease (n = 30) and healthy subjects (n = 13). The number and functional activity of circulating and cultured EPCs were determined. RESULTS: The migratory function of cultured EPCs was significantly impaired in diabetic patients without (median, 48, interquartile range, 46, 49 count/view/well) and with (median, 51, interquartile range, 46, 60 count/view/well) critical leg ischaemia and non-diabetic patients with critical leg ischaemia (median, 49, interquartile range, 47, 55 count/view/well) compared with healthy subjects (median, 63, interquartile range, 57, 65 count/view/well) (P < 0.0001). The number of circulating EPCs was lower in Type 2 diabetic patients without lower extremity vascular disease (median, 3500, interquartile range, 1600, 6600/10(6) cytometric events) than Type 2 diabetic patients with critical leg ischaemia (median, 5300, interquartile range, 2400, 11,100/10(6) cytometric events), non-diabetic patients with critical leg ischaemia (median, 5550, interquartile range, 2000, 32,100/10(6) cytometric events) and healthy subjects (median, 5400, interquartile range, 2700, 8700/10(6) cytometric events) (P = 0.413). CONCLUSIONS: The migratory function of EPCs is impaired in patients with Type 2 diabetes, even in those without critical leg ischaemia. These findings present an important new insight into the pathogenesis of impaired neovascularization and critical limb ischaemia in diabetic patients and provide avenues of future clinical study.

Polymorphisms in the DNA repair gene XRCC1 and associations with systemic lupus erythematosus risk in the Taiwanese Han Chinese population.

XRCC1 plays a central role in mammalian DNA repair processes. Two polymorphisms of XRCC1, rs1799782 (Arg > Trp at codon 194) and rs25487 (Arg > Gln at codon 399), are common in the Han Chinese population. Our objective was to analyze the relationship between these two functional single-nucleotide polymorphisms (SNPs) and systemic lupus erythematosus (SLE) in the Taiwanese Han Chinese population. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) on 172 SLE patients and 160 normal controls. Our data indicate that the frequency of A/G at codon 399 differed between patients and controls (p = 0.01; odds ratio: 1.80; 95% confidence interval: 1.17-2.75), but the allelic frequency analysis did not reveal significant differences. For the SNP at codon 194, there were no differences in either allelic or genotype frequencies between SLE patients and normal subjects. Clinical association studies of SLE symptoms revealed the involvement of the A/G polymorphism at codon 399 in SLE pathogenesis. Our results indicate that a functional SNP at codon 399 of XRCC1 is associated with the development of SLE.

Environmental risk factors associated with West Nile virus clinical disease in Florida horses.

The objective of this study was to examine the extrinsic risk factors of West Nile virus (WNV) clinical disease in Florida horses as established from confirmed and negative horses tested within the state from 2001 to 2003. An Arboviral Case Information Form (ACF) was submitted by a referring veterinarian at the time of testing to the Florida Department of Agriculture and Consumer Services on every horse suspected of a viral encephalitis in Florida. A follow-up survey that focused on arbovirus prevention and farm ecology was created and mailed to the owner of each tested horse. Data from the follow-up survey indicated peak WNV prevalence in the late summer months in Florida. Quarter horses were the most commonly affected breed. The WNV vaccine was highly protective and natural water on the property also had a protective association. Factors that increased the risk of WNV to horses were the use of fans and a stable construction of solid wood or cement. Some risk indicators were dead birds on the property and other ill animals on the property. Data from this retrospective study have helped identify factors associated with WNV transmission in equines in Florida. Horses that have not been vaccinated and show clinical signs of arboviral infection from June to November should be tested for WNV. Horses that have been vaccinated and show clinical signs should be tested when the vaccination was administered within 1 month or greater than 6 months prior to the onset of clinical symptoms associated with WN infection.

Analysis of ERCC2/XPD functional polymorphisms in systemic lupus erythematosus.

Sunlight/ultraviolet (UV) irradiation has been recognized as an important risk factor for developing systemic lupus erythematosus (SLE). However, the interpretation of genetic variations involved in UV-light sensitivity is largely unknown. Recent studies indicated that two genetic variations of ERCC2/XPD gene (rs1799793 in exon 10 and rs13181 in exon 23) have been found to exert negative influences on nucleotide excision repair system. To analyse the possible contribution of the ERCC2/XPD functional single nucleotide polymorphisms in genetic susceptibility to SLE, the rs13181 and rs1799793 SNPs in ERCC2/XPD were genotyped by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Association was studied by case-control analyses using samples from 172 SLE patients and 160 healthy controls. Haplotype analysis was performed to detect the association with genetic predisposition to SLE and the clinical features. Although these two functional genetic variations are linked to several immune dysfunction-induced diseases, no statistically significant differences in allele or genotype frequencies were observed between SLE patients and controls. Haplotype analysis showed that none of ERCC2/XPD haplotypes was associated with the incidence of SLE disease, nor the preference of clinical features. In conclusion, the ERCC2/XPD functional polymorphisms analysed in this study showed no association in genetic susceptibility to SLE.

Dementia is associated with open-angle glaucoma: a population-based study.

PURPOSE: Previous epidemiologic studies that focused on the association between open-angle glaucoma (OAG) and dementia showed inconsistent results. In the present study, we explored the association between OAG and dementia in an ethnic Chinese (i.e., Taiwanese) population using a population-based data set. METHODS: We retrieved data on study subjects for this case-control study from the Longitudinal Health Insurance Database 2000. We identified 7770 patients who had a diagnosis of dementia as cases, and 7770 subjects matched in terms of sex and age, which were randomly extracted as controls. A conditional logistic regression conditioned on age group, sex, and index year was used to assess the association of dementia with previously diagnosed OAG among the sampled patients. RESULTS: Of 15,540 patients, 1.70% had prior OAG, including 2.02% of the dementia group and 1.38% of the controls. After adjusting for patient socioeconomic characteristics and comorbid medical disorders, dementia patients were more likely to have had prior OAG than controls (odds ratio (OR): 1.44; 95% confidence interval (CI): 1.12-1.85; P<0.01). In addition, female dementia patients were more likely to have had prior OAG than controls (OR: 1.93; 95% CI: 1.35-2.77; P<0.001), whereas no statistical difference in prior OAG between male dementia patients and controls was found. CONCLUSIONS: Female dementia patients were associated with a higher proportion of prior OAG than were the controls.

Diagnosis and monetary quantification of occupational injuries by indices related to human capital loss: analysis of a steel company as an illustration.

Prevention of occupational injuries is an important task of human resource management. In this study, new indices of human capital loss of occupational injury including cumulative injury rate, proportion of potential workdays lost, and potential salary lost were applied to the analysis of registry data of occupational injuries from 1986 to 1994 of a steel company in Taiwan. In addition, we compared these indices with disabling frequency rate and severity rate. The results showed that the average disabling frequency rate and cumulative injury rate of the whole company were 4.12 and 0.41, respectively; and the average disabling severity rate and proportion of potential workdays lost of the whole company were 563 and 229 x 10(-6), respectively, during 1986-1994. There was no consistent improvement in occupational safety in this period. The average potential salary lost of the whole company was more than US$ 2 million per year with a discount rate of 0.04, which was equivalent to 92 times of average annual income of a worker. The major monetary loss were due to non-traffic injuries of operators and traffic injuries of non-operators, which amounted to US$ 145 and 152 per person per year. As the new indices can provide additional information on lifetime occupational risk and human capital loss in monetary values, we concluded that they may be useful supplementary tools for monitoring and analyzing occupational injury data in a company.

Tuberculous meningitis in a Filipino maid.

Tuberculous meningitis, while not uncommon in Taiwan, has not been reported among foreign workers. We report the first case of tuberculous meningitis in a 37-year-old Filipino maid in Taiwan, who presented with headache, fever and vomiting. She had been well before this episode and the small screening films of the chest radiograph obtained on her arrival in Taiwan 15 months previously, and every 6 months thereafter showed no evidence of tuberculosis. The suspicion of tuberculous meningitis was delayed until disturbance of consciousness manifested and a standard chest radiograph showed a diffuse miliary pattern in both lung fields. A cerebrospinal fluid sample that was sent for a polymerase chain reaction-based assay specific for Mycobacterium tuberculosis showed a positive result. The patient recovered with sequelae of mildly incoherent speech and urinary incontinence after antituberculous medication and short-course steroid treatment. Clinicians should be aware of the possibility of tuberculous meningitis in foreign workers with complaints of fever and headache. Because high-quality chest radiographs are a prerequisite for early detection of pulmonary tuberculosis, we recommended that standard posterior-anterior chest radiographs should be obtained as part of the routine health examination for foreign workers.

Bilateral anomalous origins of the posterior meningeal artery from the ascending pharyngeal arteries.

We present a rare case of angiographically confirmed dural arteriovenous fistula supplied mainly by the posterior meningeal artery with bilateral anomalous origins from the bilateral ascending pharyngeal arteries. The bilaterality of the origins of the posterior meningeal artery is important in the angiographic diagnosis and management of a dural vascular malformation in the posterior fossa or the posterior part of the falx cerebri.

LRIG1 modulates aggressiveness of head and neck cancers by regulating EGFR-MAPK-SPHK1 signaling and extracellular matrix remodeling.

EGFR overexpression and chromosome 3p deletion are two frequent events in head and neck cancers. We previously mapped the smallest region of recurrent copy-number loss at 3p12.2-p14.1. LRIG1, a negative regulator of EGFR, was found at 3p14, and its copy-number loss correlated with poor clinical outcome. Inducible expression of LRIG1 in head and neck cancer TW01 cells, a line with low LRIG1 levels, suppressed cell proliferation in vitro and tumor growth in vivo. Gene expression profiling, quantitative RT-PCR, chromatin immunoprecipitation, and western blot analysis demonstrated that LRIG1 modulated extracellular matrix (ECM) remodeling and EGFR-MAPK-SPHK1 transduction pathway by suppressing expression of EGFR ligands/activators, MMPs and SPHK1. In addition, LRIG1 induction triggered cell morphology changes and integrin inactivation, which coupled with reduced SNAI2 expression. By contrast, knockdown of endogenous LRIG1 in TW06 cells, a line with normal LRIG1 levels, significantly enhanced cell proliferation, migration and invasiveness. Such tumor-promoting effects could be abolished by specific MAPK or SPHK1 inhibitors. Our data suggest LRIG1 as a tumor suppressor for head and neck cancers; LRIG1 downregulation in cancer cells enhances EGFR-MAPK-SPHK1 signaling and ECM remodeling activity, leading to malignant phenotypes of head and neck cancers.

Genetic polymorphisms of the DNA repair gene MPG may be associated with susceptibility to rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. A previous study indicated that a DNA repair system was involved in the development of RA. In this study, we investigated the association of four N-methylpurine-DNA glycosylase (MPG) gene polymorphisms (rs3176364, rs710079, rs2858056, and rs2541632) with susceptibility to RA in 384 Taiwanese individuals (192 RA patients and 192 control subjects). Our data show a statistically significant difference in genotype frequency distributions at rs710079 and rs2858056 SNPs between RA patients and control groups (P = 0.040 and 0.029, respectively). Our data also indicated that individuals with the GG genotype at rs2858056 SNP may have a higher risk of developing RA. In addition, compared with the haplotype frequencies between case and control groups, individuals with the GCGC haplotype appeared to be at a greater risk of RA progression (P = 0.003, OR = 1.75; 95% CI = 1.20-1.55). Our results suggest that rs710079 and rs2858056 polymorphisms and the GCGC haplotype in the MPG gene are associated with the risk of RA progression, and thus may be used as molecular markers of RA if they are confirmed by further research.

Botulinum toxin for diabetic neuropathic pain: a randomized double-blind crossover trial.

BACKGROUND: Diabetic neuropathy is a common complication in diabetes, with patients typically experiencing diverse sensory symptoms including dysesthesias in the feet and usually accompanied by sleep disturbance. There is still no comprehensive understanding of the underlying biologic processes responsible for diabetic neuropathic pain. Thus, the current symptomatic therapy remains unsatisfactory. Recent experimental evidence suggests that botulinum toxin type A (BoNT/A) may not only inhibit the release of acetylcholine at the neuromuscular junctions, but also modulate afferent sensory fiber firing, thereby relieving neuropathic pain. METHODS: A double-blind crossover trial of intradermal BoNT/A for diabetic neuropathic pain in 18 patients was conducted to evaluate the effectiveness. RESULTS: We find significant reduction in visual analog scale (VAS) of pain by 0.83 +/- 1.11 at 1 week, 2.22 +/- 2.24 at 4 weeks, 2.33 +/- 2.56 at 8 weeks, and 2.53 +/- 2.48 at 12 weeks after injection in the BoNT/A group, as compared to the respective findings for a placebo group of 0.39 +/- 1.18, -0.11 +/- 2.04, 0.42 +/- 1.62, and 0.53 +/- 1.57 at the same timepoints (p < 0.05). Within the BoNT/A group, 44.4% of the participants experienced a reduction of VAS >/=3 within 3 months after injection, whereas there was no similar response in the placebo group. At the 4-week postinjection stage, improvement in sleep quality was measured using the Chinese version of the Pittsburgh Sleep Quality Index. CONCLUSIONS: This pilot study found that botulinum toxin type A significantly reduced diabetic neuropathic pain and transiently improved sleep quality. Further large-scaled study is warranted.

HLA-E gene polymorphism associated with susceptibility to Kawasaki disease and formation of coronary artery aneurysms.

OBJECTIVE: Kawasaki disease (KD) is a pediatric systemic vasculitis of unknown cause for which a genetic influence is supposed. The purpose of this study was to identify possible genetic variants in the major histocompatibility complex (MHC) region that are associated with KD and the development of coronary artery aneurysms (CAAs) in a Taiwanese population. METHODS: The 168 genetic variants covering the MHC locus were analyzed in an association study of a Taiwanese cohort of 93 KD patients and 680 unrelated healthy children matched for sex and age with the study patients. RESULTS: Eleven single-nucleotide polymorphisms (SNPs) were associated with the occurrence of KD. The SNP located at the 3'-untranslated region of HLA-E (rs2844724) was highly associated (P < 1 x 10(-7)). In addition, the frequency of the C allele was higher in KD patients without CAAs than in controls (P < 0.001) due to a significantly increased frequency of the CC and CT genotypes. Plasma levels of soluble HLA-E were significantly higher in KD patients than in controls regardless of the presence of CAAs. Furthermore, there was a trend toward higher plasma levels of soluble HLA-E in KD patients with the CT and TT genotypes of the HLA-E gene polymorphism. CONCLUSION: Our results suggest that the HLA-E gene polymorphism may play a role in the pathogenesis of KD.

A/C polymorphism in the interleukin-18 coding region among Taiwanese systemic lupus erythematosus patients.

Interleukin-18 (IL-18) is associated with chronic inflammation, autoimmune diseases and various cancers and infectious diseases. An IL-18 genetic A/C polymorphism at coding position 105 (rs549908) has been linked with asthma and rheumatoid arthritis. We tested a hypothesis that the IL-18 genetic polymorphism confers systemic lupus erythematosus (SLE) susceptibility. Study participants were Taiwanese SLE patients and a healthy control group. Our results indicate (1) a significantly higher A allele frequency in SLE patients (P = 0.003; OR = 1.97; 95% CI = 1.26-3.08) and (2) a significantly higher A allele frequency in SLE patients with a central nervous system disorder (P = 0.027; OR = 7.18; 95% CI = 0.95-54.28). Our results suggest that the A/C polymorphism contributes to SLE pathogenesis.