Promoter hypomethylation and overexpression of TSTD1 mediate poor treatment response in breast cancer.

Epigenetic alterations play a pivotal role in cancer treatment outcomes. Using the methylation array data and The Cancer Genome Atlas (TCGA) dataset, we observed the hypomethylation and upregulation of thiosulfate sulfurtransferase-like domain containing 1 (TSTD1) in patients with breast cancer. We examined paired tissues from Taiwanese patients and observed that 65.09% and 68.25% of patients exhibited TSTD1 hypomethylation and overexpression, respectively. A significant correlation was found between TSTD1 hypomethylation and overexpression in Taiwanese (74.2%, p = 0.040) and Western (88.0%, p < 0.001) cohorts. High expression of TSTD1 protein was observed in 68.8% of Taiwanese and Korean breast cancer patients. Overexpression of TSTD1 in tumors of breast cancer patients was significantly associated with poor 5-year overall survival (p = 0.021) and poor chemotherapy response (p = 0.008). T47D cells treated with TSTD1 siRNA exhibited lower proliferation than the control group, and transfection of TSTD1 in MDA-MB-231 induced the growth of MDA-MB-231 cells compared to the vector control. Additionally, overexpression of TSTD1 in MCF7 cells mediated a poor response to chemotherapy by epirubicin (p < 0.001) and docetaxel (p < 0.001) and hormone therapy by tamoxifen (p =0.025). Circulating cell-free hypomethylated TSTD1 was detected in plasma of Taiwanese breast cancer patients with disease progression and poor chemotherapy efficacy. Our results indicate that promoter hypomethylation and overexpression of TSTD1 in patients with breast cancer are potential biomarkers for poor 5-year overall survival and poor treatment response.

Automatic Detection of the Circulating Cell-Free Methylated DNA Pattern of GCM2, ITPRIPL1 and CCDC181 for Detection of Early Breast Cancer and Surgical Treatment Response.

The early detection of cancer can reduce cancer-related mortality. There is no clinically useful noninvasive biomarker for early detection of breast cancer. The aim of this study was to develop accurate and precise early detection biomarkers and a dynamic monitoring system following treatment. We analyzed a genome-wide methylation array in Taiwanese and The Cancer Genome Atlas (TCGA) breast cancer (BC) patients. Most breast cancer-specific circulating methylated CCDC181, GCM2 and ITPRIPL1 biomarkers were found in the plasma. An automatic analysis process of methylated ccfDNA was established. A combined analysis of CCDC181, GCM2 and ITPRIPL1 (CGIm) was performed in R using Recursive Partitioning and Regression Trees to establish a new prediction model. Combined analysis of CCDC181, GCM2 and ITPRIPL1 (CGIm) was found to have a sensitivity level of 97% and an area under the curve (AUC) of 0.955 in the training set, and a sensitivity level of 100% and an AUC of 0.961 in the test set. The circulating methylated CCDC181, GCM2 and ITPRIPL1 was also significantly decreased after surgery (all p < 0.001). The aberrant methylation patterns of the CCDC181, GCM2 and ITPRIPL1 genes means that they are potential biomarkers for the detection of early BC and can be combined with breast imaging data to achieve higher accuracy, sensitivity and specificity, facilitating breast cancer detection. They may also be applied to monitor the surgical treatment response.

Epidemiology of Behcet's Disease in Taiwan: A Population-Based Study.

PURPOSE: To study the incidence and epidemiology of Behcet's disease in Taiwan. METHODS: This retrospective cohort study was conducted using the nationwide reimbursement database in Taiwan. One million registered beneficiaries of the Taiwan National Health Insurance system in 2000 were randomly selected. All medical claims of these persons were collected. The definition of having Behcet's disease was based on diagnostic codes. Persons who had incomplete registry data or diagnoses prior to 2001 were excluded. Annual incidence between 2001 and 2011 was calculated and risk factors for incidence were explored using the Cox proportional regression model. Characteristics of patients with Behcet's disease with and without uveitis were compared. RESULTS: A total of 236 newly diagnosed patients with Behcet's disease were found between 2001 and 2011. The average incidence was 2.40 cases per 100,000 person-years (ranging from 1.29 to 3.53). Female patients and those aged between 40 and 65 years were at the highest risk of Behcet's disease. Only 18.2% of the patients had also suffered from uveitis. The subspecialties of doctors making initial diagnoses and the number of prescribed immunomodulatory agents differed significantly between the patients with and without uveitis (p < 0.001 and <0.05, respectively). CONCLUSION: Incidence of Behcet's disease was not high in Taiwan and relatively few of the patients developed uveitis. Patients of working age or who were female were more likely to have Behcet's disease. However, age of onset and clinical severity differed between patients with and without uveitis.

Behcet's disease with uveitis in Taiwan.

BACKGROUND: Behcet's disease is a multisystemic inflammatory disease which may lead to blindness. The purpose of this study was to describe and compare the clinical features and visual outcome of Behcet's uveitis in Taiwan. METHODS: The medical charts of 227 consecutive patients (414 eyes) with Behcet's uveitis who were seen in the Uveitis Clinic of Taipei Veterans General Hospital were reviewed: 96 patients (group A) between 1984 and 1993 and 131 (group B) between 1994 and 2003. RESULTS: The male-to-female ratio was 1.6. The mean age at the time of uveitis onset was 30.8 years. Males were most affected in the 3rd and 4th decades and females in the 2nd to 5th decades. There were more skin and gastrointestinal lesions in males, and less skin and genital lesions in group B. HLA-B51 antigen was found in 35.7% of patients. Treatment with cyclosporin, azathioprine and methotrexate was more frequent in group B. Uveitis occurred bilaterally in 83.9% of patients. At the first visit, potential visual acuity (VA) was 0.1 or less in 24.7% of eyes in males and 11.4% in females. The mean time from presentation to loss of useful vision (> 0.1) was 51 months in 19.1% of eyes. Kaplan-Meier survival analysis estimated the risks of losing useful vision at 5, 10 and 15 years as being 22.6%, 43.0% and 58.5%, respectively. VA at the first and last visits were better and VA deterioration slower in group B. CONCLUSION: Visual outcome is poorer in males than in females and has improved in the recent decade, but still a significant proportion of patients lose their vision quickly. The number of new patients has not decreased.

Severe vaso-occlusive retinopathy as the primary manifestation in a patient with systemic lupus erythematosus.

Severe vaso-occlusive retinopathy as the initial manifestation of systemic lupus erythematosus (SLE) is rare. We report a 16-year-old female who developed bilateral visual impairment. Fundus examinations showed bilateral "cherry-red spot" appearance, multiple confluent cotton wool spots, and widespread arterial occlusion. Laboratory studies showed leukopenia, antinuclear antibody (+), and anti-double-stranded DNA antibody (+). Malar rashes, oral ulcers, and bilateral knee joint tenderness were noted during physical examination. SLE was diagnosed and pulse therapy started immediately. Best corrected visual acuity of the left eye improved to 6/10 after treatment. However, there was no visual improvement in the right eye. Four months later, bilateral panretinal laser photocoagulation was performed due to retinal neovascularization. However, tractional retinal detachment of the right eye and vitreous hemorrhage of the left eye still occurred. After undergoing cryoretinopexy of the right eye and intravitreous tissue plasminogen activator injection of the left eye, the visual acuity of the patient's right eye remained hand movement only at 10 cm, but that of the left eye returned to 6/10. The ocular and systemic conditions were stable in the follow-up period of more than 2 years. This case demonstrates that in patients with severe vaso-occlusive retinopathy, a generalized immunological disorder, like SLE, should be suspected.

Uveitis with biopsy-proven sarcoidosis in Chinese--a study of 60 patients in a uveitis clinic over a period of 20 years.

BACKGROUND: The aim of this study was to assess the clinical features of uveitis with biopsy-proven sarcoidosis in Chinese patients. METHODS: This was a retrospective study of uveitis patients with biopsy-proven sarcoidosis who consecutively visited the uveitis clinic of Taipei Veterans General Hospital from 1986 to 2005. Medical records were reviewed to obtain demographic data, initial symptoms, biopsy sites, pulmonary conditions detected by chest X-ray and manifestations of uveitis. From 2002 onwards, patients also received chest computed tomography (CT). RESULTS: A total of 60 uveitis patients with biopsy-proven sarcoidosis were identified. Forty-four patients (73%) were found in the last 4 years. Female predominance with a male-to-female ratio of 1:6.5 was found. The most common initial symptom was uveitis in 41 patients (68%). The most common positive biopsy sites were mediastinal lymph nodes, lung, conjunctiva and skin. Twenty (90.9%) of 22 patients with chest X-ray stage 0 showed >or= stage 1 on CT. The mean age at uveitis onset was 47.7+/-14.7 years (range, 21-76 years), with no gender difference (p=0.913). A peak incidence was found in the 6th decade of life. There was bilateral eye involvement in 54 patients (90%). Frequency of the manifestations of uveitis showed isolated anterior uveitis in 2 patients (3.3%), isolated posterior uveitis in 8 patients (13.3%), intermediate and posterior uveitis (i.e. anterior uveitis sparing) in 16 patients (26.7%), and panuveitis in 34 patients (56.7%). CONCLUSION: A marked increase was noted since 2002. One of the causes is the performance of chest CT. Chest CT is useful to discover mediastinal lymphadenopathy and other lesions suggestive of sarcoidosis, as well as to help guide tissue confirmation in patients with peculiar uveitis features indicative of sarcoidosis. Female predominance and peak incidence of uveitis onset in the 6th decade of life were found. The posterior segment was the most common localization of uveitis in biopsy-proven sarcoidosis in Chinese.

Familial sarcoidosis in Taiwan.

Sarcoidosis is a multisystemic granulomatous disease of unknown etiology and is uncommon in Taiwan. No cases of familial sarcoidosis have been reported in Taiwan. In this article, we report a mother and son pair who had sarcoidosis. The 56-year-old mother sought medical help for chronic cough for 3 months in 1993. Enlarged mediastinal lymph nodes were demonstrated on chest computed tomography. Besides, two small erythematous papules on her face were observed. Mediastinoscopic biopsy and skin biopsy showed non-caseating granulomatous inflammation. Sarcoidosis was thus diagnosed. The human leukocyte antigen (HLA)-typing of the patient was HLA-A2, A11, B35, B39, CW4, CW7, DR8 and DQ6. Eleven years later, her son was also diagnosed with sarcoidosis proved by mediastinoscopic biopsy. His HLA-typing was HLA-A2, A24, B39, B48, CW7, CW8, DR8 and DQ6. This is the first report of familial sarcoidosis in Chinese people. More cases are needed for further investigation of genetic predisposition among Chinese people.

Rifabutin-induced hypopyon uveitis in patients with acquired immunodeficiency syndrome infected with Mycobacterium avium complex.

Rifabutin is a semi-synthetic antimycobacterial agent mainly used in the prophylaxis and treatment of Mycobacterium avium complex (MAC) in acquired immunodeficiency syndrome patients. Uveitis as a side effect of rifabutin has been recognized and established since 1994, but there was no case previously described in Taiwan so far. We report 2 cases of rifabutin-induced hypopyon uveitis in patients with human immunodeficiency virus and MAC infection. Both patients received the regimen of clarithromycin and rifabutin to treat MAC infection. Uveitis resolved after discontinuing of rifabutin and treatment with topical corticosteroid and mydriatics. Early recognition of this entity can prevent invasive ocular procedures and treatments. Doctors who prescribe rifabutin should be aware of this ocular complication of uveitis and drug-drug interactions. Ophthalmologists should put this on the list of differential diagnoses for uveitis.

Outcome of resonant voice therapy for female teachers with voice disorders: perceptual, physiological, acoustic, aerodynamic, and functional measurements.

Teachers have a high percentage of voice problems. For voice disordered teachers, resonant voice therapy is hypothesized to reduce voice problems. No research has been done on the physiological, acoustic, and aerodynamic effects of resonant voice therapy for school teachers. The purpose of this study is to investigate resonant voice therapy outcome from perceptual, physiological, acoustic, aerodynamic, and functional aspects for female teachers with voice disorders. A prospective study was designed for this research. The research subjects were 24 female teachers in Taipei. All subjects received resonant voice therapy in groups of 4 subjects, 90 minutes per session, and 1 session per week for 8 weeks. The outcome of resonant voice therapy was assessed from auditory perceptual judgment, videostroboscopic examination, acoustic measurements, aerodynamic measurements, and functional measurements before and after therapy. After therapy the severity of roughness, strain, monotone, resonance, hard attack, and glottal fry in auditory perceptual judgments, the severity of vocal fold pathology, mucosal wave, amplitude, and vocal fold closure in videostroboscopic examinations, phonation threshold pressure, and the score of physical scale in the Voice Handicap Index were significantly reduced. The speaking Fo, maximum range of speaking Fo, and maximum range of speaking intensity were significantly increased after therapy. No significant change was found in perturbation and breathiness measurements after therapy. Resonant voice therapy is effective for school teachers and is suggested as one of the therapy approaches in clinics for this population.

Conjunctival biopsy in sarcoidosis.

BACKGROUND: Conjunctival biopsy is considered to be a simple, safe and specific diagnostic procedure for sarcoidosis. This study was designed to determine the value of this procedure in Taiwan. METHODS: This study was conducted from December 2003 to April 2005 at the uveitis clinic of Taipei Veterans General Hospital. Blind sampling was conducted, obtaining a biopsy sample measuring 1 cm long by 3 mm wide from both lower fornices. A positive result was defined as the presence of non-caseating granuloma when other granuloma-forming processes had been excluded. RESULTS: Twenty-nine patients (7 men, 22 women) were enrolled. Mean age at diagnosis was 47.8 +/- 12.4 years. The most common initial symptom was eye-related problems in 19 (65.5%) patients. Of 58 biopsies, 15 (25.9%) specimens in 11 (37.9%) patients proved to be positive. Four patients experienced bilateral involvement; 7 patients had unilateral involvement. No prominent conjunctival nodules or follicles were noted. Gender, age, presence of uveitis, initial symptoms, and chest condition comparisons revealed no association between positive and negative conjunctival biopsies. CONCLUSION: Blind and bilateral conjunctival biopsy, due to its ease, safety and specificity, could be the first biopsy inpatients with clinical or chest X-ray abnormalities suggesting sarcoidosis. None of our patients with positive biopsy had nodular lesions.

Necrotizing retinitis induced by Angiostrongylus cantonensis.

PURPOSE: To describe a case of bilateral necrotizing retinitis induced by Angiostrongylus cantonensis. DESIGN: Interventional case report. METHODS: A 52-year-old Asian woman developed eosinophilic meningitis after eating several undercooked snails. One week later, sudden onset of vision loss was noted in both eyes. Widespread yellow retinal exudates were accompanied by bullous retinal detachment in both eyes. RESULTS: Angiostrongylus cantonensis infection was confirmed by positive enzyme-linked immunosorbent assay of the serum and cerebrospinal fluid, and a positive Western blot test of the subretinal fluid. After treatment with mebendazole, levamisole, and corticosteroid, these necrotizing patches regressed gradually. However, the final visual acuity was no light perception. CONCLUSIONS: Angiostrongylus cantonensis infection should be considered as one of the causes of necrotizing retinitis.

Detection of varicella-zoster virus DNA in the iris of a zoster sine herpete patient.

A 55-year-old man presented with unilateral iridocyclitis and elevated intraocular pressure (IOP) in his right eye. Varicella-zoster virus (VZV) DNA was detected by polymerase chain reaction (PCR) in the iris of a patient of Zoster Sine Herpete. No symptoms or signs of herpes zoster like neuralgia or cutaneous eruptions on forehead were noted. His iridocyclitis was treated and responded well with systemic and topical acyclovior as well as topical steroid. However, the marked elevated IOP could not be controlled by maximal dosage of anti-glaucomatous medicine. The patient underwent trabeculectomy to control his IOP. Samples of aqueous humor and iris tissue were obtained and VZV was checked by PCR. VZV virus DNA was detected from samples of the aqueous humor and iris tissue patient of Zoster Sine Herpete by PCR analysis.

Laryngotracheal involvement as the initial manifestation of relapsing polychondritis.

Relapsing polychondritis (RP) is a rare multisystemic disease characterized by recurrent inflammation of cartilaginous and noncartilaginous tissues. When laryngotracheal or bronchial cartilages are involved, the disease can be life-threatening and needs aggressive treatment. Upper airway complaints are rare as initial presentations of RP. Here, however, we present a case of RP, with initial manifestations of cough and dyspnea that were treated as bronchial asthma for 6 months. Subglottic stenosis was found in April 2003, during a bronchoscopic examination, and emergency tracheostomy was performed. Auricular and nasal chondritis and bilateral scleritis developed 3 months after tracheostomy. High doses of methylprednisolone and immunosuppressive agents were used, and active inflammation in the eyes and ears was controlled, but the patient's upper airway was completely collapsed. This case is reported with the hope of increasing awareness about the potential for early upper airway involvement in RP.

Frosted branch angiitis in two Chinese young girls.

We examined 2 relatively healthy young girls who presented with acute red eyes and blurred vision. Each patient developed thick, inflammatory infiltrates surrounding the retinal vessels creating the appearance of frosted tree branches in both eyes. Marked inflammatory reactions with cells and flare were noted in anterior chambers. One patient even had hypopyon in both eyes. Initial visual acuity ranged from 6/6.7 to 6/60. Both patients showed rapid improvement with systemic and/or topical corticosteroid therapy, and all of the affected eyes regained a visual acuity of 6/6. The clinical appearances and courses of these two patients matched the condition previously described in Japan and labeled frosted branch angiitis. Before this article, there was only one case reported in Taiwan.

Postpartum endogenous Candida endophthalmitis.

Candida albicans is the most common pathogen causing intraocular fungal infection. Postpartum endogenous Candida endophthalmitis, however, is extremely rare. We report the case of a 33-year-old postpartum woman who presented with a 5-day history of decreased vision and had a positive blood culture for C. albicans. Fundus examination showed vitreous haze and multiple pre-retinal whitish lesions with indistinct borders. Systemic investigations revealed acute renal failure and cardiomegaly. After treatment with intravenous antifungal therapy, vitrectomy, and intravitreal injection of antimycotics, systemic and intraocular infections were eradicated successfully.

Syphilitic uveitis as the initial manifestation of HIV infection.

Syphilis is an uncommon cause of uveitis in HIV-infected patients. We report a case of bilateral panuveitis and describe its characteristics as the initial manifestation of HIV infection. A 74-year-old heterosexual male complained of blurred vision and floaters in both eyes for 40 days. Slit lamp examination showed diffuse keratic precipitates and cells in the anterior chamber of both eyes. Fundus examination revealed multiple small white dots and scattered retinal hemorrhage over the mid-equatorial retina with marked vitritis. Physical examination disclosed multiple erythematous papules over bilateral palms compatible with secondary syphilis. Serologic tests--the venereal disease research laboratory (VDRL) test, fluorescent treponemal antibody absorption (FTA-ABS) test, and Treponema pallidum hemagglutination (TPHA) test--were all positive. Aqueous fluid also showed positive FTA-ABS reaction. Under the impression of acquired secondary syphilis, enzyme-linked immunosorbent assay and Western blot test were performed and revealed concurrent HIV infection. After intravenous administration of penicillin-G, 18 million units daily for 2 weeks, the vitritis and retinochoroiditis improved. All patients with panuveitis of unknown cause should undergo VDRL and FTA-ABS screening. Subsequent testing for HIV antibody in leutic uveitis is also mandatory.