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To evaluate the association between serum carotenoids and quantitative measures of retinal vasculature in elderly Singapore Chinese subjects. The following details were collected in 128 healthy subjects: sociodemographics, lifestyle information, medical and drug history, and anthropometric measurements. Serum concentrations of carotenoids were estimated in fasting venous blood using high performance liquid chromatography. Retinal vascular parameters were quantitatively measured from retinal photographs using a computer-assisted program (Singapore I Vessel Assessment). The mean age of the population was 54.1 years (range 40 to 81 years). In multiple linear regression analysis, per SD decrease in retinal arteriolar caliber [β = 0.045 (0.003 to 0.086), p = 0.036], per SD increase in retinal venular caliber [β = -0.045 (-0.086 to -0.003), p = 0.036] and per SD increase in arteriolar branching angle [β = -0.039 (-0.072 to -0.006), p = 0.021] were associated with decreased serum lutein. Per SD increase in retinal venular tortuosity [β = -0.0075 (-0.0145 to -0.0004), p = 0.039] and per SD increase in arteriolar branching angle (β = -0.0073 [-0.0142 to -0.0059], p = 0.041) were associated with decreased serum zeaxanthin. None of the other carotenoids demonstrated meaningful relationship with quantitative measures of retinal vasculature. Lower levels of lutein and zeaxanthin demonstrated significant relationship with adverse quantitative measures of retinal vasculature in elderly healthy subjects., Competing Interests: Alexandra Health Private Limited does not alter our adherence to PLOS ONE policies on sharing data and materials.

Evidence of LRRK2 haplotypes associated with Parkinson's disease (PD) risk was recently found in the Chinese population from Singapore, and a common LRRK2 missense variant, Gly2385Arg, was independently detected as a putative risk factor for PD in the Chinese population from Taiwan. To test the association between the Gly2385Arg variant in a large case-control sample of Chinese ethnicity from Singapore, and to perform functional studies of the wild type and Gly2385Arg LRRK2 protein in human cell lines. In a case-control study involving 989 Chinese subjects, the frequency of the heterozygous Gly2385Arg genotype was higher in PD compared to controls (7.3 vs. 3.6%, odds ratio = 2.1, 95% CI: 1.1-3.9, P = 0.014); these values yield an estimated population attributable risk (PAR) of approximately 4%. In a multivariate logistic regression analysis with the disease group (PD vs. controls) as the dependent variable and the genotype as an independent factor with adjustments made for the effect of age and gender, the heterozygous Gly2385Arg genotype remained associated with an increased risk of PD compared to wild type genotype (odds ratio = 2.67, 95% CI: 1.43-4.99, P = 0.002). The glycine at position 2385 is a candidate site for N-myristoylation, and the Gly2385Arg variant replaces the hydrophobic glycine with the hydrophilic arginine, and increases the net positive charge of the LRRK2 WD40 domain. In transfection studies, we demonstrated that both the wild type and Gly2385Arg variant LRRK2 protein localize to the cytoplasm and form aggregates. However, under condition of oxidative stress, the Gly2385Arg variant was more toxic and associated with a higher rate of apoptosis. Our study lends support to the contention that the Gly2385Arg is a common risk factor for PD in the Chinese population. Our bioinformatics and in-vitro studies also suggest that the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms.

A recent meta-analysis observed a greater significant inverse association of the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y variant with Parkinson's disease (PD) for Asian (predominantly Japanese) populations compared with Caucasian populations. We performed an independent case-control study in 335 PD and 341 control subjects with data from a Chinese population to investigate the age-of-onset effect of the UCHL1 variant in PD. The Y/Y and Y/S genotypes were less frequent in the PD young-onset group than in controls and the frequency of the Y alleles was higher in young controls compared to young-onset PD (age at examination

Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.

A common heterozygous leucine-rich repeat kinase 2 (LRRK2) mutation 6055G > A transition (G2019S) accounts for about 3-7% of familial Parkinson's disease (PD) and 1-1.6% sporadic PD in a number of European populations. To determine the prevalence of the G1019S mutation in our Asian population, we conducted genetic analysis of this mutation in 1000 PD and healthy controls. The G2019S mutation was not detected in any of our study subjects. The prevalence of G2019S mutation is rare (< 0.1%) in our population, suggesting that occurrence of this mutation may vary amongst different ethnic races. This has important clinical implication when implementing guidelines for genetic testing.

Background: The expression of depression in Asian temporomandibular disorder (TMD) patients may differ from that of their Caucasian counterparts. This study examined the prevalence of depressive symptoms and their association with non-specific physical symptoms (NPSs) reporting in Asian patients., Methods: Two hundred and fifty-five Asian TMD patients (68 males; 187 females) with a mean age of 33.0 years were selected for this study. Research diagnostic criteria (RDC)/TMD history questionnaire was input directly into computers by patients using the NUS TMDv.1.1 software. Symptom Checklist 90 (SCL-90) depression and NPS scales were generated online and automatically archived for statistical analysis. Data were subjected to ANOVA/Scheffe's test and Pearson's correlation at significance level 0.05 and 0.01, respectively., Results: 43.1 and 50.6% of the patients scored moderate-to-severe on the depression and NPS scales, respectively. The percentage of patients with diffuse physical symptoms remained high (45.5%), even after pain items were excluded from the computation. NPS scores ranged from 0.34 to 1.64, while depression scores ranged from 0.27 to 1.21. A significant and positive correlation (r = 0.74) was observed between depression and NPS scores., Conclusions: The prevalence of depressive symptoms and NPSs was lower in Asian TMD patients. Psychological distress experienced by female Asian TMD patients was comparable to their male counterparts. Results also suggest that depressive symptomatology is associated with the reporting of multiple NPSs.

Background: Intracranial germ cell tumours (IGCT) are rare. We present our experience in Therapeutic Radiology Department, National Cancer Centre, Singapore., Methods: A retrospective study was conducted through case notes review on 25 patients with IGCT referred between January 1988 and January 1999., Results: The median age at diagnosis was 13 years (range 6-22). The tumours were mainly pineal germinoma (72%). Median follow-up for living patients was 2.57 years (range 0.12-10.8). Median radiotherapy (RT) dose to whole brain, primary site and spine was 35.3,54 and 30 Gys respectively. Four to six cycles of BEP or JEB chemotherapy (CM) were given in 10 patients. As for the whole study group, the seven-year overall survival (OS) and recurrence-free survival (RFS) were 86% (95% CI 72-100) and 78% (95% CI 60-100) respectively. The 10-year OS and RFS were 65% (95% CI 36-100) and 78% (95% CI 60-100) respectively. The germinoma group had 75% 10-year OS and 86% 10-year RFS. Mixed germinoma and non-germinoma germ cell tumours (NGGCT) group had 50% one-year RFS and 44% two-year OS. Acute side-effects of RT and CM were minimal. There was no statistically significant difference in side-effects when treatment modalities were compared., Conclusion: In the treatment of intracranial germinoma, we recommend biopsy and CSRT. Primary chemotherapy (+/- low-dose cranial RT) should be used in the protocol or clinical trial settings. Chemo-radiotherapy is recommended for mixed germinoma and NGGCT. A multicentre trial is needed to address various controversial issues.

This postal survey was carried out in 1999 amongst dental technicians in Singapore to assess their status of training, interest towards a local dental technology course and national certification. A hundred and seven questionnaires were sent to technicians of 37 private and two institutional laboratories. Sixty technicians responded giving a response rate of 56.1%. Half of the respondents were above 40 years and more than 40% were not formally trained. Ninety-five percent (95%) agreed that there was a need for national certification. The preferred duration of a structured dental technology course was three years part-time followed by two years full-time. This study has shown that there is a need to train new and existing technicians through introduction of a local structured dental technology course and continuing education. National certification could be introduced when more technicians are formally trained.

Prospective randomized clinical trials have shown the effectiveness of combined adjuvant 5-fluorouracil-based chemotherapy and radiotherapy after surgical resection of rectal cancer. To assess toxicity of this therapy, prospective data were collected from 236 Asian rectal cancer patients treated with combined 5-fluorouracil-based chemotherapy and radiotherapy after surgery. Almost 82% of patients completed planned therapy. Grade 3 and 4 diarrhea, stomatitis, and granulocytopenia occurred in approximately 18-21% of patients. There were two treatment-related deaths from granulocytopenia and sepsis. With median follow-up of 3.5 years, median disease-free and overall survival was 75 and 88 months, respectively. In conclusion, combined adjuvant 5-fluorouracil-based chemotherapy and radiotherapy after surgical resection of rectal cancer is tolerable in Asian patients with moderate toxicity.

Background: The objective of the current study was to describe the survival of nasopharyngeal carcinoma (NPC) patients in Singapore, verify the prognostic value of the revised 1997 TNM staging system, and develop a multivariate prognostic model for NPC. In addition, the authors also examined the prognostic value of characteristics of lymph node spread and parapharyngeal involvement., Methods: A prospectively maintained database containing clinical and computed tomography scan data was used to reclassify 677 NPC patients treated between 1992 and 1994 according to the new staging system. Records were linked with the death registry to ascertain the patient's vital status and date of death. Overall and stage specific survival were analyzed using the Kaplan-Meier method and the log rank test. Univariate and multivariate Cox proportional hazards regression analysis were used to obtain prognostic models., Results: Two hundred seventy-four deaths (40.5%) occurred. The 5-year survival rate was 56.6% (95% confidence interval [95% CI], 52.3%, 60.7%). The stage specific 5-year survival rates were: Stage I, 88%; Stage IIA, 75%; Stage IIB, 74%; Stage III, 60%; Stage IVA, 35%; and Stage IVB, 28%. TNM stage was found to be a statistically significant prognostic factor (P < 0.0001). Cranial nerve (hazard ratio [HR]: 2.77), orbit (HR: 5.71), and intracranial involvement (HR: 2.46) conferred a particularly bad prognosis in univariate analysis. Independently significant prognostic factors were age; lymph node status; and paraoropharyngeal, cranial nerve, orbit, and nasal involvement. Among lymph node positive patients, independently significant prognostic lymph node characteristics were Ho level and laterality. Although parapharyngeal involvement appeared to be prognostically unimportant, paraoropharyngeal involvement distinguished a subgroup with a poorer prognosis (HR: 1.84; 95% CI, 1.45, 2.34; P < 0.0001). Lateral spread to the medial infratemporal fossa and beyond also was found to confer a poorer prognosis., Conclusions: The results of the current study show that the revised 1997 TNM staging system is prognostically useful. Subdivision into paraoropharyngeal involvement and using the medial infratemporal fossa to delineate prognostically significant lateral spread should be considered in future revisions., (Copyright 1999 American Cancer Society.)

Clinical experience of arthroscopy in 12 temporomandibular joints with a clinical diagnosis of closed lock was described. There were 10 patients and all were females with a mean age of 31.2 years (range 20 to 59 years). The antero-lateral approach was used for entry into 11 joints. The clinical findings were adhesions (64%), fibrillation (64%), anterior displacement of disc (36%) and scuffing of the articular surface of the glenoid fossa (9%). Two of the joints that had arthrocentesis prior to arthroscopy did not show any different findings from the rest. Of the 8 patients who had pre-arthroscopy pain, 7 patients (88%) had reduction of the symptom. Three patients (38%) had complete resolution of pain. The range of mouth opening (measured as maximal incisor opening) increased in all patients two weeks following arthroscopy. The average change in maximal incisor opening was 40.3% with a range of 22% to 85%. The mean follow-up was 34 months (range 4 to 68 months).

A retrospective analysis was done of 49 patients treated for testicular seminoma over a 15-year period between January 1980 and April 1995 at the Department of Therapeutic Radiology, Singapore General Hospital. Their mean age was 39 years and their median period of follow-up was 67 months. Using the Royal Marsden Staging classification, 35 (71.4%) were stage I, 10 (20.4%) were stage II, I (2%) was stage III, and 3 (6.1%) were stage IV. Five (10.2%) arose in undescended testes. Thirty-six patients were treated with inguinal orchidectomy and postoperative radiotherapy to the para-aortic and ipsilateral iliac nodes. Eight had para-aortic and bilateral iliac irradiation, and 2 had ipsilateral pelvic, para-aortic, mediastinal and supraclavicular lymph node irradiation. Six of the patients had, in addition, irradiation of the inguinal-scrotal area. Nine received both chemotherapy as well as radiotherapy. The median dose of radiation given was 30.67 Gy and where a boost was required, the median total tumour dose was 35.75 Gy. The actuarial relapse-free survival at 10 years was 88.9% and the actuarial overall survival at 10 years was also 88.9%. Long-term treatment toxicities were uncommon.

An arthroscopic study on 22 temporomandibular joints in 13 cadavers was undertaken. Dissections were carried out to correlate the arthroscopic with macroscopic findings in the joints. Iatrogenic damage to the temporomandibular joints and their surrounding tissues was also examined. Correlation between arthroscopy and macro findings was 91.0%. There was no damage to the facial nerve and superficial temporal vessels. Iatrogenic damage to the temporomandibular joint included scuffing of the articular surfaces of the glenoid fossa and articular eminence (31.8%), scuffing of the condylar articular surface (9%), one disc perforation (4.5%) and one perforation of the medial capsule (4.5%). Prevention of iatrogenic injuries is discussed.

In April 1986, an outbreak of pruritic rash occurred among workers in a warehouse in Jurong and affected 18 out of the 46 workers within one week. The rash was papular and distributed mainly over the thighs, abdomen and the upper limbs. Epidemiological investigations were carried out to determine the cause of the outbreak and the mode of transmission. As the warehouse was colonised by a local species of wild birds (Mynahs) and badly littered with bird-droppings during the outbreak period, samples of bird excreta and feathers were sent for identification of tick, mite, flea and other ectoparasites. The aetiology of the outbreak was confirmed when a flea caught from the body of one of the affected workers was identified as Ceratophyllus gallinae (Schrank), a bird-flea. Furthermore, when the bird-droppings were cleaned up and the premises fogged with insecticide and made bird-proof, no further case of dermatitis was reported. This is the first documented report of a bird-flea causing an outbreak of dermatitis in Singapore.

This study analyses the results of primary radiotherapy for 44 patients with early glottic cancer (Tis, T1 stage) given at the Therapeutic Radiology Department, Singapore General Hospital during the 4-year period from 1978 to 1981. Irradiation was delivered using cobalt teletherapy with free set-ups, and without "air-gap" compensation. Total doses of 55Gy to 64Gy were given in daily fractions of 1.8Gy, treating five times a week. The crude 5-year survival rate for Tis/T1a tumours was 88.9% and for T1b lesions, 81%. On correcting for deaths from intercurrent disease, the survival rates improved to 95.5% and 92.6% respectively. In 33 cases where the quality of voice after radiation was assessed, 15 patients (45.4%) retained good voice quality with an additional 11 patients (33.3%) having acceptable voice quality. In seven cases the voice after radiation was rated as poor. Nine patients had local recurrence, giving a rate of 20.4%. One other patient had cervical node metastasis and subsequently developed lung secondaries. Surgery, solely or with re-irradiation, was an effective treatment for local recurrence. Re-irradiation alone failed to control any case with recurrence.

A nation-wide outbreak of 260 cases of DF/DHF with 1 death occurred in Singapore from Apr-Sept 1986. The outbreak originated from 3 separate foci of transmission at the western, south-eastern and north-eastern parts of the island and then spread to other dengue receptive urban and suburban areas. The morbidity rate was highest in young male Chinese adults between 15 and 24 years of age. The outbreak was rapidly brought under control through destruction of adult Aedes mosquitoes, surveys and source reduction of larval breeding habitats, health education and to a certain extent law enforcement. The Aedes population was high in the main foci of transmission although the overall house index was only 1.1. Other factors which could have precipitated the outbreak included waning herd immunity of the human population and continuous introduction of dengue virus into the country.

This is a descriptive study to establish the profile of 120 consecutive patients seeking relief from symptoms and dysfunction of the masticatory system at the Dental Clinic, Singapore General Hospital from February 1988-September 1988. The mean age of the patients was 29.4 years and females outnumber males by 2:1. The patients complained of TMJ clicking (66%), TMJ pain (55%), painful chewing (47%), headaches (42%), painful opening (37%), jaw locking (33%), and jaw muscle pain (23%). The possible etiological factors were recorded: macrotrauma (27%), stressful episodes (24%), unilateral mastication (53%), clenching (28%), grinding (26%) and excessive chewing habits (10%). Unilateral chewing was significantly associated with pain on opening (p less than 0.05) and joint pain (p less than 0.05). A statistical relationship was found between night grinding and laterotrusive wear of teeth (p less than 0.001). There was evidence that tension headache reported by TMD sufferers was related to temporalis muscle/tendon dysfunction (p less than 0.001).

The results of 76 cases of advanced colorectal carcinoma treated at the Department of Therapeutic Radiology, Singapore General Hospital, from 1977 to 1978, are presented. All cases had "Curative" Surgery and were given adjuvant radiotherapy or chemotherapy or both. All were adenocarcinoma and had lymph node involvement as well as tumour infiltration through the bowel wall. 44 cases of rectal carcinoma were given radiotherapy to the pelvis followed by I/V 5-fluorouracil for at least one year. 32 cases of colon cancer were given I/V 5-fluorouracil for at least one year. 20 of these cases had cancer of the sigmoid colon and were given pelvic irradiation as well. The five year actuarial survival rates were 27.8% for rectal cancer and 24.3% for colon cancer.

The construction of dams across the mouths of major tidal rivers in the development of the Kranji Reservoir, Western Catchments Scheme and the Sungei Seletar Reservoir in Singapore created suitable environmental conditions for the propagation of anopheline brackish-water breeders. The employment of foreign contract workers from malarious areas for the projects further increased the potential risk of malaria transmission. However, constant vigilance and environmental management aimed at the permanent elimination of vector breeding habitats, supplemented with chemical control and anti-parasite measures successfully prevented the reintroduction of malaria in these highly receptive and vulnerable areas.