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Biomedical subjects

G H Tan

Publications and source records attributed to G H Tan.

At least 19 recordsLinked to original sources

Comparison of bioengineered human bone construct from four sources of osteogenic cells.

Osteoprogenitor cells have been reported to be present in periosteum, cancellous and cortical bone, and bone marrow; but no attempt to identify the best cell source for bone tissue engineering has yet been reported. In this study, we aimed to investigate the growth and differentiation pattern of cells derived from these four sources in terms of cell doubling time and expression of osteoblast-specific markers in both monolayer cells and three-dimensional cell constructs in vitro. In parallel, human plasma derived-fibrin was evaluated for use as biomaterial when forming three-dimensional bone constructs. Our findings showed osteoprogenitor cells derived from periosteum to be most proliferative followed by cortical bone, cancellous bone, and then bone marrow aspirate. Bone-forming activity was observed in constructs formed with cells derived from periosteum, whereas calcium deposition was seen throughout the constructs formed with cells derived from cancellous and cortical bones. Although no mineralization activity was seen in constructs formed with osteoprogenitor cells derived from bone marrow, well-organized lacunae as would appear in the early phase of bone reconstruction were noted. Scanning electron microscopy evaluation showed cell proliferation throughout the fibrin matrix, suggesting the possible application of human fibrin as the bioengineered tissue scaffold at non-load-bearing sites.

Bone and Bones↗

The use of bone marrow stem cells for bone tissue engineering.

Bone marrow stem cells (BMSC), known for its multipotency to differentiate into various mesenchymal cells such as chodrocyte, osteoblasts, adipocytes, etc, have been actively applied in tissue engineering. BMSC have been successfully isolated from bone marrow aspirate and bone marrow scraping from patients of various ages (13-56 years) with as little as 2ml to 5ml aspirate. BMSC isolated from our laboratory showed the presence of a heterogenous population that showed varying prevalence of surface antigens and the presence of telomerase activity albeit weak. Upon osteogenic induction, alkaline phosphatase activity and mineralization activity were observed.

Bone Marrow Cells↗

Strategy for generating tissue-engineered human bone construct.

The strategy used to generate tissue-engineered bone construct, in view of future clinical application is presented here. Osteoprogenitor cells from periosteum of consenting scoliosis patients were isolated. Growth factors viz TGF-B2, bFGF and IGF-1 were used in concert to increase cell proliferation during in vitro cell expansion. Porous tricalcium phosphate (TCP)-hydroxyapatite (HA) scaffold was used as the scaffold to form 3D bone construct. We found that the addition of growth factors, greatly increased cell growth by 2 to 7 fold. TCP/HA proved to be the ideal scaffold for cell attachment and proliferation. Hence, this model will be further carried out on animal trial.

Bone Regeneration↗

A direct high-performance liquid chromatographic method for the determination of therminol 66 contamination in commercial glycerin and fatty acids.

A simple and sensitive high-performance liquid chromatographic method for the determination of Therminol 66 thermal heating fluid in glycerin and fatty acids is developed. Sample solutions dissolved in methanol-tetrahydrofuran (50:50, v/v) are injected directly into a reversed-phase C18 column and eluted with a methanol and water mixture (88:12, v/v). The concentration of the thermal heating fluid is monitored by fluorescence detection at 257 nm (excitation) and 320 nm (emission). The calibration graph obtained from various concentrations of the thermal heating fluid in the methanol and tetrahydrofuran mixture is linear (correlation coefficient = 0.999), and the limit of detection is 0.01 microg/mL. Spiked glycerin containing 0.1 to 1.0 microg/g of the thermal heating fluid also gives good linearity with a mean recovery of 95.3%. The mean intra- and interassay precision are 1.80-6.51% and 5.71-9.03%, respectively, at the 0.1-microg/g level. The method is simple and does not require any pretreatment step, thus it is ideal for quality assurance purposes.

Journal Article↗

Risk factors for predicting mortality in a paediatric intensive care unit.

Rapid advances in critical care technology and rising cost of medical care have spurred the development of outcome analysis including mortality risk prediction. The main objective of this study was to assess the risk factors contributing to mortality in our paediatric intensive care unit (PICU). This is a cohort study, consisting of consecutive admissions to the PICU from 1 January to 31 December 1997. The factors studied included multi-organ dysfunction syndrome (MODS), Pediatric Risk of Mortality III (PRISM III) scores in the first 24 hours (PRISM III-24), mechanical ventilation, renal replacement therapy, age, and diagnosis-related groups. Univariate and multivariate statistical methods were used. Univariate analysis showed that need for mechanical ventilation, renal replacement therapy, presence of MODS involving 3 or more organs and PRISM III-24 scores were significantly associated with outcome (P < 0.0005). Relative risk of mortality in the presence of MODS and PRISM III-24 scores > or = 8 were 11.3 (95% CI: 3.3 to 38.3) and 15.8 (95% CI: 2.0 to 127.8), respectively. Using Cox Proportional Hazards model, the relative risk of mortality for any new admission could be calculated by the equation RR = e0.1032 x P, where P = PRISM III-24 scores.

Adolescent↗

Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging.

BACKGROUND: The introduction of highly sensitive imaging techniques has made it possible to detect many non-palpable nodules, or "incidentalomas," in the thyroid. Discovery of these lesions raises concerns about their malignancy, but the optimal strategy for managing these lesions has not been clearly established. PURPOSE: To review evidence about incidentalomas, including prevalence and risk for malignancy, and to provide recommendations for their evaluation and treatment. DATA SOURCES: Literature searches for relevant articles published in the past 15 years in major English-language medical journals, review of selected articles published before this period, and reviews of bibliographies in text-books. STUDY SELECTION: Three studies on autopsy findings, 11 studies on ultrasonographic findings, and other reports on nonpalpable thyroid nodules were included. DATA EXTRACTION: Data on the prevalence of nodules on autopsy and in ultrasonographic series, palpation compared with ultrasonography, the risk for malignancy in nodules found in irradiated glands, the natural history of thyroid nodules, and the prevalence of occult cancer were collated and reviewed. DATA SYNTHESIS: Prevalence of thyroid incidentalomas estimated from autopsy studies ranges from 30% to 60%. Studies comparing clinical palpation with thyroid imaging show a prevalence of 13% to 50%. Prospective studies of randomly selected patients have reported a prevalence of 19% to 67%. The risk for malignancy in asymptomatic nodules found in nonirradiated glands is 0.45% to 13% (mean +/- SD, 3.9% +/- 4.1%). CONCLUSIONS: High-resolution ultrasonography is sensitive and capable of detecting many small, nonpalpable thyroid nodules. Most of these lesions are benign. For most patients with nonpalpable nodules that are incidentally detected by thyroid imaging, simple follow-up neck palpation is sufficient.

Autopsy↗

Management of thyroid nodules in pregnancy.

BACKGROUND: Disorders of the thyroid are common in pregnancy. In particular, a thyroid nodule is frequently discovered before or during pregnancy. OBJECTIVE: To develop guidelines for the management of thyroid nodules during pregnancy. METHODS: We reviewed the cases of 40 pregnant patients with thyroid nodules evaluated during a 10-year period Cytological findings were compared with available histological findings, and concordance rates were determined. The rank sum test was used for statistical analysis. RESULTS: Fine-needle aspirations of thyroid nodules in 62% of patients were benign cytologically (25 patients). Of 8 patients with negative cytological results who had thyroidectomy, all had benign disease histologically (100% concordance rate). Cytological findings of papillary cancer (3 patients) strongly correlated with final histological diagnosis (100% concordance rate), whereas papillary cancer was confirmed histologically in only 2 of 4 patients with cytological findings suspicious for this disease (50% concordance rate). All 3 nodules with cytological findings suspicious for follicular neoplasm were benign adenomas histologically. Of 2 nodules suspicious for Hürthle cell neoplasm, l was Hürthle cell adenoma and the other was Hürthle cell carcinoma (100% concordance rate). Thyroidectomy during the second trimester of pregnancy or the early postpartum period was successful. CONCLUSIONS: The approach to thyroid nodules in pregnancy should be similar to that for nonpregnant patients. Thyroidectomy should be performed (1) during the second trimester for malignant lesions and cytological findings suspicious for papillary cancer and (2) in the postpartum period for cytological findings suspicious for follicular neoplasm.

Adult↗

MELAS- and Kearns-Sayre-type co-mutation [corrected] with myopathy and autoimmune polyendocrinopathy.

A 35-year-old woman with features of Kearns-Sayre syndrome consisting of progressive ptosis, ophthalmoparesis, mitochondrial myopathy, and pigmentary retinopathy also had autoimmune polyglandular syndrome type 11 (Addison's disease, autoimmune insulin-dependent diabetes mellitus, Hashimoto's thyroiditis, and primary ovarian failure). There was no history of similarly affected relatives. Analysis of muscle mitochondrial DNA (mtDNA) revealed a 2,532-bp deletion of the type seen in Kearns-Sayre syndrome as well as a heteroplasmic A3243G mutation in the tRNA-Leu(UUR) gene of the type seen in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). The patient's blood and her mother's blood harbored the A3243G mutation but not the deletion, and the maternal grandmother's blood had neither mutation. In muscle, the species of mtDNA harboring the deletion was exclusively associated with the species harboring the A3243G mutation, suggesting that the point mutation predisposed to the large-scale deletion. The mtDNA species with both mutations accounted for 88% of total muscle mtDNA. Other and as yet unrecognized point mutations in mtDNA might also be associated with, and possible causally related to, large-scale mtDNA deletions.

Adult↗

Pharmacologic treatment options for non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health concern for clinicians who are responsible for the care of an aging population. The relationship between hyperglycemia and the chronic complications of retinopathy, nephropathy, and neuropathy has been established in patients with insulin-dependent diabetes mellitus, and it is extremely likely that such a relationship exists in patients with NIDDM as well. Diet and exercise are the cornerstone for the management of NIDDM. The assessment of glycemic control should determine which patients with NIDDM need more aggressive intervention to control hyperglycemia. Pharmacologic treatment options include oral administration of the sulfonylureas, a biguanide, and an alpha-glucosidase inhibitor and subcutaneous administration of insulin. Extensive education about diabetes and self-monitoring of blood glucose levels are important components in maximizing glycemic control. Additional pharmacologic treatment options are necessary when adequate individualized treatment goals are not attained. The goal of therapy is to prevent the onset or progression of long-term microvascular and macrovascular complications. In this review, we present the therapeutic options and outline our approach to the pharmacologic treatment of NIDDM. Relevant medical literature on each treatment modality is reviewed, and the cost of therapy with use of each medication is provided.

Acarbose↗

Coexistence of bilateral adrenal phaeochromocytoma and idiopathic hyperaldosteronism.

The coexistence of phaeochromocytoma and primary aldosteronism is rare. In the four cases reported in the English literature, adrenal gland involvement was unilateral. The case we report is unusual in that both adrenal glands were affected. Our patient was a 63-year-old man who presented with long-standing hypertension and hypokalaemia. Evaluation for secondary hypertension showed biochemical evidence of both phaeochromocytoma and primary aldosteronism. Bilateral adrenal masses were found on imaging studies. Right total and left partial adrenalectomy were performed. Pathological examination revealed bilateral phaeochromocytomas, with cortical findings consistent with mild cortical hyperplasia. Annual biochemical evaluation over a 2-year period has shown no evidence of recurrent disease. To our knowledge, this is the first reported case in the English-language literature of phaeochromocytomas involving both adrenal glands coexisting with hyperaldosteronism.

Adrenal Gland Neoplasms↗

Interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptor inhibit IL-1-induced glycosaminoglycan production in cultured human orbital fibroblasts from patients with Graves' ophthalmopathy.

An accumulation of glycosaminoglycans (GAG) is a feature characteristic of orbital connective tissues from patients with Graves' ophthalmopathy (GO) that leads directly to the clinical expressions of the disease. Interleukin-1 (IL-1), produced by macrophages and fibroblasts within the diseased orbit, stimulates GAG synthesis by orbital fibroblasts. We designed the current study to determine whether particular agents might block this effect and thus be useful in the treatment of GO. Orbital fibroblast cultures were grown to confluence and incubated for 48 h with IL-1 (1-10 U/mL) alone or IL-1 (10 U/mL) in combination with IL-1 receptor antagonist (IL-1ra; 1-40 ng/mL) or soluble IL-1 receptor (sIL-1R; 0.25-10 micrograms/mL). Cells were labeled with [3H]glucosamine and processed for GAG quantitation. The addition of IL-1 alone stimulated GAG synthesis by 73-176% (mean, 104%; P < 0.05). Significant inhibition of IL-1-stimulated GAG synthesis was observed after treatment of normal fibroblasts with IL-1ra at a concentration of 5 ng/mL (12.5-fold molar excess; mean, 33%; P < 0.05); essentially complete inhibition was achieved at 40 ng/mL (100-fold molar excess; mean, 86%; P < 0.05). Significant inhibition of GAG synthesis by sIL-1R was observed at a concentration of 0.5 microgram/mL (720-fold molar excess; mean, 79%; P < 0.05), and inhibition was essentially complete at 1 microgram/mL (1440-fold molar excess; mean, 89%; P < 0.05). IL-1ra and sIL-1R are potent inhibitors of IL-1-induced GAG production by cultured human orbital fibroblasts. Our results suggest that these two compounds, shown in early trials to be safe when administered parenterally, may be useful in the prevention or treatment of GO.

Cells, Cultured↗

Comparison of solvent extraction and solid-phase extraction for the determination of organochlorine pesticide residues in water.

Solid-phase extraction (SPE) of organochlorine pesticide residues from environmental water samples was evaluated using octadecyl (C18)-bonded porous silica. The efficiency of SPE of these pesticide residues from reagent water samples at 1-5 micrograms dm-3 levels was compared with those obtained by solvent extraction with hexane and Freon TF (trichlorotrifluoroethane). Average recoveries exceeding 80% for these organochlorine pesticides were obtained via the SPE method using small cartridges containing 100 mg of 40 microns C18-bonded porous silica. The average recovery by solvent extraction with hexane and Freon TF exceeded 90% in both instances. It was concluded that the recoveries and precision for the SPE of organochlorine pesticides were poorer than those for the solvent extraction method. Organochlorine pesticide residue levels in environmental water samples from two major rivers flowing through predominantly rice-growing areas were monitored by gas chromatography using the solvent extraction method with hexane. Exceptionally high levels of organochlorine pesticide residues such as BHC, DDT, heptachlor, endosulfan and dieldrin were found in these water samples.

Chromatography, Gas↗

Tussock moth dermatitis: evidence for histamine involvement.

Moth hairs shed by the few tussock moths caught during the first documented outbreak of pruritic dermatitis in Singapore were investigated to provide evidence for the presence of histamine. Aqueous extract of the moth hairs was used for the test and analyses. In the isolated guinea pig ileum, the extract, like histamine, produced responses that were blocked by mepyramine. The high performance liquid chromatographic (HPLC) analysis of the fluorescamine derivative of the moth extract resulted in a fluorescent peak with exactly the same retention. time as the histamine fluorescamine derivative. The mass spectrum of the pentafluoropropionic acid (PFP) derivative of the extract was also identical to that obtained from the reference histamine-PFP derivative. We concluded that histamine was present in the tussock moth hairs and was involved as one of the inflammatory mediators responsible for the pruritic skin rashes.

Animals↗

Nickel sensitivity in Singapore.

Nickel is the most common cause of allergic contact dermatitis in Singapore, resulting in positive reactions in patch tests between 7 and 14%. Women are more commonly affected and have an earlier mean age of onset than men (21 compared with 32). Wrist watches, earrings, buttons, and necklaces are the common source of nickel allergy. Twenty-five percent of patients also had some form of associated hand eczema. Thirty-six percent of patients had a history of atopy showing a higher incidence than the normal populations. Thirty-seven percent of patients had an associated positive reaction to cobalt.

Adolescent↗