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Antineoplastic agents. 380. Isolation and X-ray crystal structure determination of isoaaptamine from the Republic of Singapore Hymeniacidon sp. and conversion to the phosphate prodrug hystatin 1.

By use of bioassay (murine P388 lymphocytic leukemia cell line) guided isolation procedures, extracts of the Republic of Singapore marine sponge Hymeniacidon sp. were found to contain demethyloxyaaptamine (1) and aaptamine (3) as prominent cancer cell growth inhibitory constituents accompanied by the trace, albeit more active, component isoaaptamine (4). The isolation, X-ray structure elucidation, and antineoplastic and antimicrobial activities of isoaaptamine (4) have been summarized. Because of instability, isoaaptamine (4) was converted to a stable sodium phosphate prodrug designated hystatin 1 (7).

Animals↗

Sensitization to local dust-mite fauna in Singapore.

BACKGROUND: Recent studies showed the presence of a unique dust-mite fauna in the indoor environment of Singapore. Immediate hypersensitivity to these dust mites, along with other known indoor allergens, may play a role in the pathogenesis of allergic respiratory diseases. This study evaluated the sensitization rates of the local atopic population to these allergens. METHODS: The skin prick test was performed on a total of 391 individuals (289 patients with asthma and/or allergic rhinitis and 102 healthy controls) using extracts of six species of local dust mites (Austroglycyphagus malaysiensis, Blomia tropicalis, Dermatophagoides pteronyssinus, D. farinae, Sturnophagoides brasiliensis, and Tyrophagus putrescentiae) and 10 other common indoor allergens. Total serum IgE and specific IgE to these dust mites were also quantified with the fluorescence allergosorbent test (FAST). RESULTS: The sensitization rates among patients with asthma and/or allergic rhinitis to dust mites and other inhalant allergens tested (via skin prick tests) were as follow: B. tropicalis (96.2%), D. pteronyssinus (93.4%), D. farinae (92.3%), A. malaysiensis (78.2%), S. brasiliensis (71.6%), T. putrescentiae (71.3%), canary feathers (69.9%), Periplaneta americana (cockroach) (59.5%), Blattella germanica (cockroach) (56.4%), mosquito (Aedes sp.) (46.4%), dog epithelia (mixed breed) (34.3%), kapok seed (31.8%), cat hair (29.1%), Aspergillus fumigatus (20.8%), Penicillium notatum (18.0%), and Candida (Monilia) albicans (9.3%). All patients were observed to react to at least three of the six dust-mite extracts, with 254/289 (87.9%) reacting to at least five or to all six. Skin prick responses to the dust mites were found to correlate with the corresponding specific IgE levels quantified by FAST (P<0.001). In addition, specific IgE levels to D. pteronyssinus and D. farinae were highly correlated (Spearman's rank coefficient = 0.76, P<0.001), as were those to B. tropicalis and A. malaysiensis (r = 0.60, P<0.001). CONCLUSIONS: Asthma and/or allergic rhinitis patients were highly sensitized to the local dust-mite fauna. Thus, these dust mites should be considered important allergenic sources of this region.

Adolescent↗

A multiple regression approach to study optical components of myopia in Singapore school children.

PURPOSE: Previous studies on the optical components of childhood myopia adjusted only for age and gender or reported only the change of individual components with time. We perform a study to assess the association of the optical components of the eye contributing to the degree of myopia by building a statistical model which can better assess the individual effects of each optical component. METHODS: Children 6-12 years old with myopia of -1 to -6 D were used in this study. Autokeratometry was performed to determine the mean corneal power in two perpendicular meridia. Ultrasonography was used to determine the vitreous chamber depth (VCD). Ultrasonography and Scheimflug biometry were used to determine lens thickness (LT) and anterior chamber depth. A stepwise multiple linear regression was used to determine statistically significant independent variables that explain the variation in the mean spherical equivalent of the left eye. The independent variables investigated were anterior chamber length, LT, VCD, mean corneal power, age and gender. The first regression model used measurements of anterior chamber depth and LT from ultrasonography, while the second model used measurements from Scheimflug photography. Statistical significance was set at p < 0.05. RESULTS: Both statistical models have the same significant independent variables - VCD, LT and gender, with similar estimates. In both models, VCD was found to have the strongest partial association with mean spherical equivalent, followed by gender and LT. A more myopic refractive error was associated with (1) a longer eye, (2) an increased LT, and (3) female gender. CONCLUSIONS: Myopia was associated with a longer vitreous chamber. This remained the primary determinant of myopia in Chinese children after consideration of other optical components. The effect of gender and LT on myopia requires further study. These results are in agreement with multiple regression analyses in Singapore adults.

Anterior Chamber↗

Screen detected breast cancer in an Asian population: pathological findings of the Singapore breast screening project.

We document the pathological characteristics of 135 cancers detected in 132 predominantly Chinese women in the Singapore breast screening project. Thirty-four (25%) screen detected tumours were in situ ductal cancers; 98 (73%) invasive, while three (2%) women with malignant fine needle aspirate smears refused further treatment. The median size of in situ cancers was 10 mm; the majority (56%) demonstrated a comedo pattern. Of the invasive tumours which had a median size of 15 mm, three (3%) were microinvasive, 75 (77%) infiltrative ductal, three (3%) invasive lobular, and the remaining 17 (17%) special types or others. Histologic grading revealed 23 (24%) grade I, 52 (53%) grade II, 19 (19%) grade III and four (4%) ungraded cases. Sixty-three (65%) of the invasive cancers were node negative, while 64% of all screen detected malignancies were Stages 0 (in situ) or I. From the pathological perspective, problems of borderline lesions, microinvasion, grade assessment and histological subtyping have to be addressed.

Journal Article↗

An international comparison of women's occupational health issues in the Philippines, Thailand, Malaysia, Canada, Hong Kong and Singapore: the CIDA-SEAGEP study.

BACKGROUND: An international comparison study of women's occupational health issues was carried out in 2000 for the Philippines, Thailand, Malaysia, Canada, Hong Kong and Singapore. The study was funded by the Canadian International Development Agency's Southeast Asia Gender Equity Program. AIM: The objective was to compare the issues, risk factors, social determinants, and challenges in women's occupational health, according to the status of economic development as defined by the World Bank. METHOD: Data were collected through 27 key informant interviews of high-ranking government officials and senior researchers, self-administered questionnaires on country or regional statistics and 16 courtesy calls. RESULTS: Results indicated that women's occupational health problems common in these countries or regions included women's long hours of work (double workday), shift work and a caring role for family and friends. Problems reported in developing countries but not developed countries included poor access to training and protective equipment, and insufficient legislation to protect women's rights. Problems reported in developed countries but not in developing countries included obesity, smoking and not including women in health research. CONCLUSION: This paper provides insights into the changing environment in the workplace, such as increasing participation of women in the paid workforce and changes in gender differences due to the changing country economy, for improving women's occupational health.

Adult↗

Deletion analysis of DMD/BMD children in Singapore using multiplex polymerase chain reaction (PCR) technique.

Twenty-three children suffering from Duchenne/Becker muscular dystrophy (DMD/BMD) in Singapore were analysed using the multiplex polymerase chain reaction (PCR) technique. Deletions were found in 14 cases. One rare case of total deletion of all nine exons was observed. This is the first DMD/BMD deletion analysis on South East Asian children. This technique for screening deletions was informative in 61 per cent of the local cases and would be useful for rapid diagnosis of deletion cases of DMD/BMD.

Adolescent↗

Actinopolymorpha singaporensis gen. nov., sp. nov., a novel actinomycete from the tropical rainforest of Singapore.

A novel actinomycete was isolated from soil in the tropical rainforest of Singapore. The cells of this actinomycete are highly pleomorphic. In the early stages of growth, most cells are of irregular squarish shape and varied sizes. Cells remain attached after cell division, often forming chains or aggregates of a few cells. Cells at the end of a chain tend to elongate. With prolonged cultivation, cells show different degrees of elongation and enlargement, producing branched hyphae of uneven thickness. At the periphery of the colony, long hyphae form, which are divided into alternating segments of elongated cells and chains of squarish cells. This actinomycete is considerably salt-tolerant, able to grow in the presence of 15% NaCl. Chemotaxonomically, it contains LL-diaminopimelic acid (DAP) in the cell wall, type PI phospholipids and MK-9(H6) as the predominant menaquinone. 16S rDNA sequence analysis assigned this actinomycete to the family Nocardioidaceae, but its 16S rDNA shared no more than 91.2% sequence similarity with other members of the family. Based on phenotypic, chemotaxonomic and phylogenetic evidence, it is proposed that this actinomycete be classified as a new species in a new genus, Actinopolymorpha singaporensis gen. nov., sp. nov.

Actinomycetales↗

Investigational use of ribavirin in the treatment of severe acute respiratory syndrome, Singapore, 2003.

OBJECTIVE: Ribavirin is a broad spectrum nucleoside analogue efficacious in the treatment of several viral infections. In the recent severe acute respiratory syndrome (SARS) outbreak, ribavirin was used in various countries against this novel coronavirus. We conducted a retrospective analysis to assess the efficacy of ribavirin in the treatment of SARS in Singapore. METHODS: A total of 229 cases were analysed. Ninety-seven (42.4%) patients received ribavirin at a mean of 6.4 days of illness. Clinical and laboratory parameters taken at the start of ribavirin treatment were compared with day 5, 6 or 7 parameters of those patients not on treatment. The two groups were compared using Fisher's exact test and Student's t-test. Multivariate analysis was performed using Cox regression model with death as the outcome of interest. RESULTS: The treatment group had younger women with more symptoms of myalgia (P < 0.001). The crude death rate was 12.9% in the control and 10.3% (P = 0.679) in the treatment group. After correction for age, male sex, lactate dehydrogenase levels and steroid use, the hazard ratio was 1.03 (95% CI: 0.44-2.41, P = 0.939). CONCLUSION: In this retrospective, uncontrolled cohort analysis, use of ribavirin did not appear to confer any benefit for patients with SARS.

Adult↗

Etretinate therapy for psoriasis and other keratinizing disorders: a 10-year retrospective study in Singapore.

BACKGROUND: Etretinate, a second generation retinoic acid, has been reported to be useful in the treatment of psoriasis and other keratinizing disorders. The effectiveness of etretinate for these disorders are studied in a 10-year retrospective study of all patients treated with etretinate in a skin clinic in Singapore. METHODS: The case records of 190 cases of psoriasis and other keratinizing disorders treated with etretinate were analyzed. Information collected included demographic data, dosage of etretinate taken, response and side effects, clinical follow-up, and relapse. RESULTS: Most of the cases (72.6%) had psoriasis (138/190). The others had different keratinizing disorders. The dose of etretinate used was 0.15 to 1 mg/kg/day (median 0.36 mg/kg/day), and the duration of the treatment varied from 1 to 120 months (median 6 months). Etretinate was coadministered with UVB (ReUVB) or PUVA (RePUVA) in 89 (46.8%) patients. In psoriasis, the response to treatment was excellent in 41.3% (57/138), good in 36.2% (50/138), fair in 15.9% (22/138), and poor in 6.5% (9/138) of the cases. Patients with plaque-type psoriasis did better with combination therapy than with monotherapy. Those with keratinizing disorders showed excellent, good, fair, and poor responses in 32.7% (17/52), 32.7% (17/52), 25.0% (13/52), and 9.6% (5/52) respectively. Adverse effects were noted in 102 (53.7%) cases and were generally mild and tolerable. Etretinate was discontinued in 24 (12.6%) patients due to significant toxicity. CONCLUSIONS: Etretinate is effective for treating psoriasis and other keratinizing disorders. Combination therapy is preferred in chronic plaque psoriasis. Adverse effects are common, but mild and tolerable.

Adolescent↗

Isotretinoin therapy in acne vulgaris: a 10-year retrospective study in Singapore.

BACKGROUND: The use of isotretinoin, a first generation synthetic retinoid, in the treatment of patients with severe acne vulgaris was a major therapeutic advance in dermatology. This 10-year retrospective study reviews the effectiveness of isotretinoin in patients with acne vulgaris seen in a skin clinic in Singapore. METHODS: The case records of 250 cases of severe inflammatory and nodulocystic acne treated with isotretinoin were analyzed with reference to the demographic data, response to isotretinoin, dosage and cost of isotretinoin used, adverse effects, clinical follow-up, and relapse. RESULTS: Two hundred and fifty patients, 171 men (68.4%) and 79 women (31.6%), with different types and grades of acne vulgaris were studied. The dose of isotretinoin used ranged from 0.33 to 1.0 mg/kg/day (median 0.5 mg/kg/day) for a period ranging from 1 to 12 months (median 4 months). Response was excellent in 127 (50.8%) patients, good in 86 (34.4%), fair in 30 (12.0%) and poor in 7 (2.8%). Relapse occurred in 14 (5.6%) patients over a 6-month follow-up period. Adverse effects were noted in 140 (56.0%) patients and were mild in most cases. Eighteen (7.2%) patients had to discontinue the drug due to significant side effects. CONCLUSION: This study confirms that isotretinoin is very effective for severe acne, and complete remission can be induced in more than 90% of cases even with lower dosage regimens. Significant clinical improvement can be achieved with the use of lower doses (mean 0.5 mg/kg/day) for an average of 4 months of treatment with lower risk of adverse effects.

Acne Vulgaris↗

Anterior resection using the circular stapling instrument: a Singapore experience.

The circular stapler was used for colorectal anastomosis in 38 patients (rectal carcinoma 37 cases, sigmoid diverticulitis one case). In Singapore Chinese patients, the most commonly used cartridge size was the EEA 28 mm and ILS 29 mm. The incidence of clinical anastomotic leakage in patients with complete resection rings was 10% (three leaks in 32 patients), leakage occurring only amongst the 24 patients who had resection of a tumour 6-9 cm from the anal verge. Significant, though easily dilatable, stenosis occurred in three patients (8%), and was associated with rectal membrane formation in two patients. Local recurrence, occurring in seven patients in a 0.5-3 year follow-up period was associated with Dukes' C disease; two recurrences occurred in four patients in whom the distal bowel clearance was less than 1.5 cm. The circular stapler facilitates sphincter conservation in mid-rectal cancer and its use in low anterior resection is justifiable when performed with a distal bowel clearance of 2 cm and complete excision of pararectal tissue above the pelvic floor muscles.

Adult↗

Solitary rectal ulcer syndrome: the clinical entity and anorectal physiological findings in Singapore.

The clinical pattern and physiological abnormalities in solitary rectal ulcer syndrome (SRUS) occurring in Singapore, were investigated. Since April 1989, 25 patients have presented with histologically proven SRUS. There were 13 males and 12 females (20 Chinese, 4 Malay and 1 Indian) with a mean age of 47.5 (+/- 3.1) years. Ninety-six per cent presented with rectal bleeding, 92% strained at stools, 40% had mucus discharge, 40% felt incomplete defecation and 32% digitated to defecate. Four had previous haemorrhoidectomies that did not cure their symptoms. The lesions were at a mean 6.8 (+/- 0.5) cm above the anal verge, usually anteriorly (64%) but one was circumferential. Anorectal physiology performed on 14 patients was compared with 13 age and gender matched normal controls. The measured mean resting perineum level in SRUS (1.4 +/- 0.3 cm) was significantly lower than in normals (P < 0.01). The mean anal electrosensory threshold (2.5 +/- 0.52 mV) was also significantly higher than in the controls (P < 0.05). Fifteen patients were successfully treated with a high fibre diet and avoidance of straining. Three patients required surgery and the most recent seven patients have responded well to biofeedback treatment. Awareness of this uncommon anorectal condition is necessary for early diagnosis and appropriate management. The physiological findings support a pelvic straining pathophysiology resulting in perineal descent, with less sensitive rectal mucosa prolapsing into, and raising, the anal canal electrosensory threshold. Treatment strategies aimed at correcting the straining have usually been successful.

Anal Canal↗

Genitoperineal gangrene: experience in Singapore.

BACKGROUND: The experience with genitoperineal gangrene at the Department of Colorectal Surgery, Singapore General Hospital is documented. METHODS: The results of 12 patients treated during the 5 year period between 1 January 1990 and 31 January 1995 were studied. There were 10 men and two women. The mean age of the patients was 55.2 (range 37-83) years. RESULTS: Perianal pain and swelling were the commonest presentation. However, three patients were admitted in a toxic state with mental confusion. The gangrene progressed from anorectal sepsis in six patients. Five of these patients had diabetes mellitus. Escherichia coli was the commonest organism cultured. Early diagnosis, immediate resuscitation, antibiotics and early aggressive surgery was our management policy. Applying these principles, all except two patients survived (mortality 17%). One had advanced malignancy and the other had extensive burn injuries. CONCLUSIONS: A high index of suspicion should be maintained in patients with diabetes and with anorectal sepsis. Should genitoperineal gangrene develop, aggressive surgery is often successful.

Adult↗

Comparative study of TRUE Test and Finn Chamber patch test techniques in Singapore.

This is a report on a comparative study of the reactivity of TRUE Test and Finn Chamber patch test techniques. 413 patients attending a contact dermatitis clinic in Singapore were simultaneously patch tested with panels 1 and 2 of the TRUE Test standard series and with corresponding allergens (Hermal, Hamburg) using Finn Chambers. The left/right application of the TRUE Test and Finn Chambers was randomized. The concordance of positive patch test reactions to the 2 test techniques was studied. The number of patient with positive reactions was 38% and 42% for TRUE Test and Finn Chamber techniques, respectively (n.s.). The overall concordance of positive patch test reactions was 64% (209/328). 13% (42/328) of positive reactions appeared on TRUE Test only and 24% (77/328) on Finn Chamber only. When only relevant positive reactions were considered, the concordance rate was 67%; 11.6% of positive reactions appeared on TRUE Test only and 21% on Finn Chamber only. Positive reactions to p-phenylenediamine (PPD) and neomycin were more frequent with the Finn Chamber technique than with TRUE Test, i.e., false negative reactions to PPD and neomycin were more likely to occur with TRUE Test. It appeared that the TRUE Test and Finn Chamber techniques were comparable when used for patch testing. However false negative and false positive patch test reactions can occur when using either technique.

Adolescent↗

Antimicrobial susceptibilities of clinical isolates of Acinetobacter baumannii from Singapore.

The in vitro activities of 17 antimicrobial agents alone or in combination against 70 clinical isolates of Acinetobacter baumannii from Singapore were determined by broth microdilution. The MICs of amoxicillin, ampicillin, ceftazidime, ceftriaxone, gentamicin, and piperacillin for 90% of the strains were > or = 128 micrograms/ml. Addition of sulbactam to ampicillin produced improved activity, whereas adding tazobactam to piperacillin did not. The MICs of amikacin, ciprofloxacin, and imipenem for 90% of the strains were 32, 32, and 16 micrograms/ml, respectively.

Acinetobacter↗

Functional genomics analysis of Singapore grouper iridovirus: complete sequence determination and proteomic analysis.

Here we report the complete genome sequence of Singapore grouper iridovirus (SGIV). Sequencing of the random shotgun and restriction endonuclease genomic libraries showed that the entire SGIV genome consists of 140,131 nucleotide bp. One hundred sixty-two open reading frames (ORFs) from the sense and antisense DNA strands, coding for lengths varying from 41 to 1,268 amino acids, were identified. Computer-assisted analyses of the deduced amino acid sequences revealed that 77 of the ORFs exhibited homologies to known virus genes, 23 of which matched functional iridovirus proteins. Forty-two putative conserved domains or signatures were detected in the National Center for Biotechnology Information CD-Search database and PROSITE database. An assortment of enzyme activities involved in DNA replication, transcription, nucleotide metabolism, cell signaling, etc., were identified. Viruses were cultured on a cell line derived from the embryonated egg of the grouper Epinephelus tauvina, isolated, and purified by sucrose gradient ultracentrifugation. The protein extract from the purified virions was analyzed by polyacrylamide gel electrophoresis followed by in-gel digestion of protein bands. Matrix-assisted laser desorption ionization-time of flight mass spectrometry and database searching led to identification of 26 proteins. Twenty of these represented novel or previously unidentified genes, which were further confirmed by reverse transcription-PCR (RT-PCR) and DNA sequencing of their respective RT-PCR products.

Animals↗

Heterogeneity of Chinese medical herbs in Singapore assessed by fluorescence AFLP analysis.

There are conflicting records on the identity of Chinese medical herbs, and it is known that different plant materials are used under the same common names in different regions in China. However, there is no study on the genetic heterogeneity of medical herbs in any market outside of China. In this report, Chinese medical herbs under common names Radix Quinquefolii (American Ginseng or Xiyangshen), Radix Astragali (Huangqi), Radix Notoginseng (Tianqi), Coxtex Cinnamomum (Guipi), Radix Isatidis (Banlangen), Radix Codonopsis (Dangshen) and Radix Rehmannia (Shengdi) were collected from three independent herbal shops in Singapore and their DNAs were isolated and subjected to fluorescence Amplified Fragment Length Polymorphism (AFLP) analysis. While samples for Radix Quinquefolii and Radix Astragali were homogenous genetically [similarity index (SI) = 0.85-1.00] across the three shops, genetic heterogeneity was found for the other herbs (SI < 0.7). For example, four samples of Radix Codonopsis were of three distinct patterns (SI < 0.6). Our results highlight the situation that genetically distinct herbal materials are labeled and marketed under the same common names in an international market of Chinese medical herbs, which may contribute to inconsistency in quality and efficacy.

China↗

Five-year follow-up of a clinical trial of three 6-month regimens of chemotherapy given intermittently in the continuation phase in the treatment of pulmonary tuberculosis. Singapore Tuberculosis Service/British Medical Research Council.

In a study in Singapore, patients of Chinese, Malay, and Indian ethnic origin with sputum-smear-positive pulmonary tuberculosis were allocated at random to daily treatment with streptomycin, isoniazid, rifampin, and pyrazinamide for 2 months (2SHRZ), for 1 month (1SHRZ), or for 2 months without streptomycin (2HRZ), followed, for all patients, by 3-times-weekly isoniazid and rifampin (H3 R3) up to 6 months. As previously reported, all except 1 of 319 patients with drug-susceptible tubercle bacilli pretreatment had a favorable bacteriologic status at the end of chemotherapy, and among the 300 patients assessed up to 30 months (24 months after the end of chemotherapy), there was only 1 bacteriologic relapse in each series, giving an overall therapeutic failure rate of only 1.3%. Follow-up has been continued at 6-month intervals up to 5 yr. During the 5 yr, the total relapse rate for patients with drug-susceptible strains pretreatment was 2.4% of 297 patients (95% confidence limits, 1.0 to 4.8%). Among the 31 patients with strains resistant to isoniazid, streptomycin, or both drugs pretreatment, there were no failures during chemotherapy and 4 (13%) subsequent relapses.

Antitubercular Agents↗