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Biomedical subjects

M H Tan

Publications and source records attributed to M H Tan.

At least 19 recordsLinked to original sources
PubMed2006

Gene therapy progress and prospects: the eye.

The eye has unique advantages as a target organ for gene therapy of both inherited and acquired ocular disorders and offers a valuable model system for gene therapy. The eye is readily accessible to phenotypic examination and investigation of therapeutic effects in vivo by fundus imaging and electrophysiological techniques. Considerable progress has been made in the development of gene replacement therapies for retinal degenerations resulting from gene defects in photoreceptor cells (rds, RPGRIP, RS-1) and in retinal pigment epithelial cells (MerTK, RPE65, OA1) using recombinant adeno-associated virus and lentivirus-based vectors. Gene therapy also offers a potentially powerful approach to the treatment of complex acquired disorders such as those involving angiogenesis, inflammation and degeneration, by the targeted sustained intraocular delivery of therapeutic proteins. Proposals for clinical trials of gene therapy for early-onset retinal degeneration owing to defects in the gene encoding the visual cycle protein RPE65 have recently received ethical approval.

Clinical Trials as Topic↗
PubMed2006

Thymic carcinoid in multiple endocrine neoplasia 1: genotype-phenotype correlation and prevention.

Thymic carcinoid is a rare multiple endocrine neoplasia type 1 (MEN1)-associated tumour that is a major cause of death in MEN1 patients. Here, we describe a previously unreported MEN1 family in which two siblings presented with malignant thymic carcinoids. All six siblings share a novel nonsense mutation Q395X on exon 8 of the MEN1 gene. The index patient developed a thymic carcinoid despite an earlier prophylactic transcervical thymectomy, and one other sibling had an incidental malignant thymic carcinoid discovered following prophylactic thymectomy, both cases demonstrating the weakness and strength of this surgical approach. We then review the spectrum of germline MEN1 mutations associated with thymic carcinoids to evaluate the possibility of a genotype-phenotype correlation. In the 22 separate MEN1 families with thymic carcinoids, all but two (91%) have mutations coding for a truncated protein. There is clearly a high prevalence of truncating mutations in MEN1-related thymic carcinoids although when compared with the prevalence of truncating mutations in all reported MEN1 mutations, it is not statistically significant (P = 0.39). Further studies are warranted to evaluate pathways of tumorigenesis of thymic carcinoids with regard to loss of function of menin.

Adult↗
PubMed2005

Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this analysis was to examine the long-term effects of pioglitazone or gliclazide addition to failing metformin monotherapy and pioglitazone or metformin addition to failing sulphonylurea monotherapy in patients with type 2 diabetes. METHODS: Two 2-year, randomised, multicentre trials were performed in patients with inadequately controlled type 2 diabetes (HbA1c 7.5-11% inclusive), who were receiving either metformin or a sulphonylurea at > or = 50% of the maximum recommended dose or at the maximum tolerated dose. In the first study, patients on metformin received add-on therapy with pioglitazone (15-45 mg/day, n = 317) or gliclazide (80-320 mg/day, n = 313). In the second study, patients on sulphonylurea therapy were randomised to receive add-on therapy with either pioglitazone (15-45 mg/day, n = 319) or metformin (850-2,550 mg/day, n = 320). HbA(1)c, fasting plasma glucose, insulin and lipids were investigated. RESULTS: At week 104, the mean reduction from baseline in HbA(1)c was 0.89% for pioglitazone and 0.77% for gliclazide addition to metformin (p = 0.200). There was a statistically significant between-group difference for the change in mean fasting plasma glucose at week 104 (-1.8 mmol/l for pioglitazone vs -1.1 mmol/l for gliclazide, p < 0.001). There were no significant differences in changes from baseline in glycaemic parameters for pioglitazone compared with metformin addition to sulphonylurea therapy. Whether added to metformin or sulphonylurea, pioglitazone caused significantly greater decreases in triglycerides and significantly greater increases in HDL cholesterol than the comparator regimens (p < or = 0.001). There were decreases in LDL cholesterol in the comparator groups and these were significantly different from the small changes observed with pioglitazone (p < 0.001). All treatment regimens were well tolerated. There were weight increases of 2.5 kg and 3.7 kg in the pioglitazone and 1.2 kg in the gliclazide add-on groups, and there was a mean decrease of 1.7 kg in the metformin add-on group. CONCLUSIONS/INTERPRETATION: As add-on therapy to existing sulphonylurea or metformin therapy, pioglitazone improved glycaemic control and this improvement was sustained over 2 years. Furthermore, there were potential benefits in terms of improvements in specific lipid abnormalities. This could offer an advantage over the addition of other oral agents in the long-term treatment of diabetes.

Adult↗
PubMed2005

Long-term effects of pioglitazone and metformin on insulin sensitivity in patients with Type 2 diabetes mellitus.

AIM: Despite their comparable glycaemic effects in patients with Type 2 diabetes mellitus (T2DM), pioglitazone and metformin may have different effects on insulin sensitivity because they have different mechanisms of action. We studied the changes in insulin sensitivity, as assessed by the Quantitative Insulin Sensitivity Check Index (QUICKI), in patients with T2DM who used metformin or pioglitazone as monotherapy or in combination therapy with sulphonylurea. METHODS: Data in this report are from two multicentre, randomized, double-blind, double-dummy studies conducted in Europe (monotherapy) or in Europe and Canada (combination therapy study). Patients were randomized to 52 weeks of treatment consisting of a 12-week forced titration period and a 40-week maintenance period. HbA(1c), fasting plasma glucose (FPG) and fasting serum insulin (FSI) were quantified from a single blood sample at weeks 0, 8, 16, 24, 32, 42 and 52. Insulin sensitivity was assessed with QUICKI, which is calculated from FSI and fasting blood glucose (FBG) concentrations using the formula 1/(log(10) FSI + log(10) FBG). Time course effects of the treatments were compared by repeated measures analysis of covariance. RESULTS: As monotherapy, pioglitazone and metformin increased QUICKI compared with baseline (baseline vs. end point [mean +/- sem]; pioglitazone [0.303 +/- 0.001 vs. 0.321 +/- 0.001; P < 0.001] and metformin [0.304 +/- 0.001 vs. 0.315 +/- 0.001; P < 0.001]). Pioglitazone increased insulin sensitivity more than metformin from week 4 through week 52. There were significant increases in QUICKI from baseline in both combination therapy groups (baseline vs. end point; pioglitazone + sulphonylurea [0.305 +/- 0.001 vs. 0.319 +/- 0.001; P < 0.001] and metformin + sulphonylurea [0.306 +/- 0.001 vs. 0.317 +/- 0.001; P < 0.001]). Overall, pioglitazone + sulphonylurea significantly increased insulin sensitivity more than metformin + sulphonylurea. CONCLUSION: Pioglitazone differed from metformin in its effects on insulin sensitivity despite both drugs having comparable glycaemic effects.

Adult↗
PubMed2005

Delayed diagnosis of Ewing's sarcoma of the right humerus initially treated as chronic osteomyelitis: a case report.

We report a case of limited stage Ewing's sarcoma which was initially treated as chronic osteomyelitis for 3 years. A 24-year-old man presented with a one-week history of pain in the right arm and fever, with histology suggestive of osteomyelitis of the affected humerus. He developed multiple relapses of pain and fever; each episode responded to antibiotic treatment. A second biopsy was performed 3 years later and confirmed a diagnosis of Ewing's sarcoma. Despite a 3-year delay in diagnosis, the disease remained localised. This case report highlights an atypical facet of the natural history of Ewing's sarcoma: a response to antibiotic and anti-inflammatory agents, and the limited stage of the disease despite a misdiagnosis of 3 years. This suggests the possibility that anti-inflammatory agents exert an inhibitory effect on the tumour growth. We also highlight the newer histologic and immunologic staining used in the diagnosis of Ewing's sarcoma.

12E7 Antigen↗
PubMed2005

Treatment of benign giant cell tumours of bone in Singapore.

INTRODUCTION: Giant cell tumour (GCT) is a distinct neoplasm of undifferentiated cells. The exact cell of origin is unknown. The multinucleated giant cells present are formed from the fusion of mononuclear cells. Giant cell tumour is more common in Southeast Asia than in the West. The incidence is about 20% compared to 4% to 5% in the West. MATERIALS AND METHODS: Sixteen patients with giant cell tumour were treated in the Singapore General Hospital from 1993 to 2001. The average follow-up period was 64.4 months, with a range of 30 to 132 months. The average age of the patients was 33 years. The tumours were divided into 3 groups. The first group had meticulous curettage and high-speed burring followed by methylmethacrylate cementation. The second group had treatment similar to the first but in addition had an adjuvant treatment with liquid nitrogen, hydrogen peroxide or phenol before cementation of the cavity. The third group had wide resection done. There were 9 in the first group, 5 in the second group and 2 in the third group. The tumours were graded radiologically after the method of Campanacci et al. All patients were followed up clinically and radiologically. Of the 5 in the second treatment group, 1 had phenol irrigation, 2 had cryotherapy and 2 had hydrogen peroxide irrigation intraoperatively. RESULTS: There was a total of 5 recurrences (31%). The 2-year recurrence-free survivorship was 75%. The mean recurrence period was 21 months. There were no complications like fracture, infection or thermal injury to the skin. There was no pulmonary metastasis or mortality. The first group, who had curettage, high-speed burr and cementation, had 44% (4 out of 9) recurrence; the second group, who had treatment like the first with additional adjuvant therapy, had no recurrence; and the third, who had wide resection, had 50% (1 out of 2) recurrence. All the recurrences had a Campanacci grade II or III tumour. There were no recurrences in the group that was treated with curettage, high-speed burr, adjuvant treatment and cementation. CONCLUSION: Currettage, high-speed burring with added phenol/liquid nitrogen treatment and cementation is a useful and safe method in the treatment of giant cell tumours. The advantages include a low recurrence rate, as well as immediate stabilisation allowing early mobilisation. Patients who have Campanacci grade I tumours have the highest chance of being disease-free after the first operation.

Adult↗
PubMed2004

The effects of oral anti-hyperglycaemic medications on serum lipid profiles in patients with type 2 diabetes.

AIM: Patients with type 2 diabetes often have dyslipidaemia, putting them at risk of cardiovascular disease, and are frequently treated with oral anti-hyperglycaemic medications (OAMs). This review compares the effects of OAMs on serum lipids [total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and free fatty acids (FFAs)] in patients with type 2 diabetes. METHODS: medline was searched for entries indexed from January 1966 to November 2002; search terms included the names of OAMs and serum lipids, limited to English language and human subjects. We selected clinical studies in type 2 diabetes of OAM monotherapy that included serum lipid data, treated all patients in a treatment group with the same drug, used therapeutic OAM doses not higher than the maximum recommended in the USA, compared therapy with baseline or placebo and specified statistical tests used. One unblinded investigator selected studies for inclusion. Data reported include number of patients, study length, OAM dose, serum lipid data at baseline and endpoint, p-values and statistical tests. RESULTS: Data on the serum lipid effects of sulphonylureas, repaglinide, nateglinide and miglitol were inconclusive. Acarbose increased HDL-C and decreased LDL-C and voglibose reduced TC. Metformin at higher doses reduced TC; data on its effects on other lipids were inconclusive. Rosiglitazone increased LDL-C, HDL-C and TC and reduced FFAs but had no effect on TGs. Pioglitazone increased HDL-C and reduced TGs and FFAs but did not affect LDL-C or TC. CONCLUSIONS: Lipid changes as a result of improved glycaemic control are not uniform findings associated with anti-diabetic therapy. Only metformin, acarbose, voglibose, rosiglitazone and pioglitazone had significant effects on the lipid profile. These effects should be considered when selecting OAMs for patients with type 2 diabetes.

Administration, Oral↗
PubMed2004

Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with Type 2 diabetes.

AIMS: This study compared the effects of 52 weeks' treatment with pioglitazone, a thiazolidinedione that reduces insulin resistance, and glibenclamide, on insulin sensitivity, glycaemic control, and lipids in patients with Type 2 diabetes. METHODS: Patients with Type 2 diabetes were randomized to receive either pioglitazone (initially 30 mg QD, n = 91) or micronized glibenclamide (initially 1.75 mg QD, n = 109) as monotherapy. Doses were titrated (to 45 mg for pioglitazone and 10.5 mg for glibenclamide) to achieve glycaemic targets during the next 12 weeks: fasting blood glucose of < or = 7 mmol/l and 1-h postprandial blood glucose of < or = 10 mmol/l. Patients were maintained on the titrated dose for 40 weeks. RESULTS: Pioglitazone significantly increased insulin sensitivity compared with glibenclamide, as assessed by homeostasis model assessment (17.0% vs. -13.0%; P < 0.001), quantitative insulin sensitivity check index (0.011 vs. -0.007; P < 0.001) and fasting serum insulin (-1.3 pmol/l vs. 23.8 pmol/l; P = 0.007). The glibenclamide group had significantly lower HbA1c than the pioglitazone group after 12 weeks of therapy (7.8% vs. 8.3%, P = 0.015), but significantly higher HbA1c after 52 weeks of therapy (7.8% vs. 7.2%, P = 0.001). Pioglitazone significantly (vs. glibenclamide) increased mean HDL-C (P < 0.001), decreased mean triglycerides (P = 0.019), and decreased mean atherogenic index of plasma (AIP; P = 0.001) and mean total cholesterol/HDL-C (P = 0.004), without significantly elevating mean total cholesterol or mean LDL-C compared with glibenclamide. CONCLUSIONS These data suggest that the effects of pioglitazone are more sustained than those of glibenclamide for improving insulin sensitivity in patients with Type 2 diabetes, and that 52 weeks' treatment with pioglitazone has favourable effects on glycaemic control and lipoprotein profile.

Blood Glucose↗
PubMed2004

Renal neoplasia in the hyperparathyroidism-jaw tumor syndrome.

Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a familial multi-tumor syndrome resulting from mutations in the HRPT2 tumor suppressor gene, which encodes a protein product named parafibromin. We review current knowledge of the renal manifestations of the HPT-JT syndrome, and examine recent advances in understanding the biological function of parafibromin.

Bone Neoplasms↗
PubMed2003

Fibrosarcoma of the brachial plexus presenting in childhood.

We report a case of malignant fibrosarcoma involving the brachial plexus presenting in childhood. Primary malignant tumours of the brachial plexus are rare entities. In particular, fibrosarcoma of the brachial plexus occurring in a child has not been previously reported. Dilemmas in resolving the management and long-term consequences of this condition are discussed.

Arm↗
PubMed2003

Delayed post-surgical development of dural arteriovenous fistula after cervical meningocele repair.

A 34-year-old female patient presented with an intracranial subarachnoid hemorrhage and was found to have a dural arteriovenous fistula at the site of previous cervical meningocele repair. Subsequent occlusion was achieved with endovascular embolization. To our knowledge, the phenomenon of the development of a spinal dural fistula at the site of a meningocele repair has not been recorded before.

Adult↗
PubMed2002

The clinician meets the computer--uneasy bedfellows.

The transformation of healthcare has been one of the great, but unfulfilled, promises of the information technology revolution. This disappointment has been due in part to the enormously complex processes involved in bedside clinical care. Selective adoption of advances in information technology has resulted in enhancement of point-of-care healthcare delivery, medical record management and professional communication. However, the introduction of these refinements has encountered resistance, as well as sparked new challenges. The exciting progress in this field is reviewed, with reference to global and local developments.

Attitude of Health Personnel↗
PubMed2001

The Torg--Pavlov ratio in cervical spondylotic myelopathy: a comparative study between patients with cervical spondylotic myelopathy and a nonspondylotic, nonmyelopathic population.

STUDY DESIGN: A radiologic study to compare the Torg--Pavlov ratios between patients with cervical spondylotic myelopathy and a nonspondylotic, nonmyelopathic population. OBJECTIVES: To determine and compare the Torg--Pavlov ratios between the two groups of patients. SUMMARY OF BACKGROUND DATA: Patients with congenital cervical spinal canal stenosis are more likely to develop cervical spondylotic myelopathy. The Torg--Pavlov ratio eliminates errors related to magnification, a problem with determination of spinal canal stenosis from direct measurements of plain cervical spine radiographs. There has only been one other study that directly compares the Torg--Pavlov ratio between patients with cervical spondylotic myelopathy and a normal control population. METHODS: The preoperative plain lateral cervical spine radiographs of 28 patients with cervical spondylotic myelopathy requiring surgical decompression were compared with radiographs of 88 nonspondylotic, nonmyelopathic patients. The Torg--Pavlov ratio was computed for each level from C3 to C7. RESULTS: The study showed that the Torg--Pavlov ratio is significantly smaller (P < 0.001) in myelopathic patients (mean 0.72 +/- 0.08) compared with the control patients (mean 0.95 +/- 0.14). This was so when individual levels and the mean values were compared. Age was also found to be a significant factor (P = 0.002), although lesser in magnitude when compared with the Torg--Pavlov ratio (P = 0.0001). CONCLUSIONS: The Torg--Pavlov ratio is significantly lower in patients with cervical spondylotic myelopathy compared with a nonspondylotic, nonmyelopathic population. It could possibly be used to predict the likelihood of developing cervical spondylotic myelopathy.

Adolescent↗
PubMed2001

The evaluation of aluminum oxide crystal microdermabrasion for photodamage.

BACKGROUND: Aluminum oxide crystal microdermabrasion has recently become popular for facial rejuvenation. Although it is a widely used technique with perceptible benefits, the clinical efficacy on photodamaged skin has yet to be established. OBJECTIVE: To measure and quantify the effect of microdermabrasion on photodamaged skin. METHODS: Ten subjects underwent one treatment a week for five to six treatments. Skin surface roughness, topography, elasticity, stiffness, compliance, temperature, sebum content, and histology were analyzed. RESULTS: Subjectively, seven patients noticed a mild improvement. Physician analysis of clinical photography indicated mild improvement in the majority of patients. Objectively, immediately following treatment skin temperature increased, sebum content decreased, and a temporary increase in skin roughness and mild flattening of some wrinkles occurred. Dynamic skin analysis demonstrated a perceptible decrease in skin stiffness and an increase in skin compliance. Histology showed slight orthokeratosis and flattening of rete ridges and a perivascular mononuclear cell infiltrate, edema, and vascular ectasia in the upper reticular dermis 1 week after completion of the series of treatments. CONCLUSION: Immediately following the procedure, changes occurring in skin characteristics can be measured that are consistent with mild abrasion and increased blood flow. Objective biomechanical analysis demonstrated a statistically significant decrease in skin stiffness and an increase in skin compliance consistent with persistent edema. Subjectively, patients and physicians report a mild improvement in the majority of subjects. Histology showed dramatic vascular changes in the reticular dermis below the level of direct abrasion. The effect of negative pressure may result in these vascular changes.

Aluminum Oxide↗
PubMed2001

Limited application of fluticasone propionate ointment, 0.005% in patients with psoriasis of the face and intertriginous areas.

BACKGROUND: Facial and intertriginous skin is more susceptible to corticosteroid-induced atrophy. Dosing regimens are needed for long-term management of corticosteroid-sensitive sites. OBJECTIVE: The safety and efficacy of 0.005% fluticasone propionate ointment were assessed in the short-and long-term management of moderate to severe psoriasis of facial and intertriginous areas compared with nonfacial, nonintertriginous areas. METHODS: Affected areas in 20 patients with psoriasis were treated twice daily for 2 weeks, then once daily for 2 consecutive days every week for 8 more weeks. RESULTS: More than 50% improvement occurred after 2 weeks (day 15) in 100% of facial and intertriginous lesions and was maintained during long-term therapy in more than 85% of facial and intertriginous lesions. More than 50% improvement for nonfacial, nonintertriginous areas reached only 80% by day 15. Recurrence rates for facial and intertriginous areas were lower than in the nonfacial, nonintertriginous areas. Skin atrophy and telangiectasia did not occur. Facial and intertriginous sites responded more quickly to topical fluticasone propionate ointment than nonfacial, nonintertriginous skin. CONCLUSION: Limited application of fluticasone propionate ointment over a period of 10 weeks is effective and delays lesion recurrence without causing skin atrophy in patients with moderate to severe psoriasis in areas at risk for corticosteroid application, such as facial and intertriginous areas.

Administration, Topical↗