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Biomedical subjects

H T Ong

Publications and source records attributed to H T Ong.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of T cells as carriers for systemic measles virotherapy in the presence of antiviral antibodies.

Neutralizing antiviral antibodies (Abs) can hinder systemic virotherapy. Here, we used activated T cells as carriers to deliver oncolytic measles viruses (MV) to multiple myeloma xenografts in the presence of anti-MV antibodies (Abs). Virus-infected T cells expressing measles H/F fusogenic envelope glycoproteins could efficiently transfer MV infection by heterofusion, even after exposure to virus-inactivating anti-MV antisera. Severe-combined immunodeficiency (SCID) mice bearing subcutaneous or disseminated human myeloma xenografts were given MV-luciferase (MV-Luc) or MV-Luc-infected T cells intravenously. Indium111 labeling indicated that 1-2% of the virus-infected T cells trafficked to tumors. Preinfected T cells fused with tumor cells in vivo and transferred MV-Luc to tumor xenografts where intratumoral viral spread was monitored non-invasively using bioluminescent imaging. In mice passively immunized with high titers of measles immune serum, intravenous virus and cell delivery were both inhibited. Decreasing the amount of measles immune serum given to mice permitted tumor infection by virus-infected T cells and cell-free virus. In conclusion, virus-loaded T cells may facilitate systemic measles virotherapy in the presence of antiviral Abs and they warrant further investigation as potential MV cell carriers.

Animals↗
PubMed2005

The statin studies: from targeting hypercholesterolaemia to targeting the high-risk patient.

The landmark HMG-CoA reductase inhibitor (statin) studies have practical lessons for clinicans. The 4S trial established the importance of treating the hypercholesterolaemic patient with cardiovascular heart disease. Next, WOSCOPS showed the benefit of treating healthy, high-risk hypercholesterolaemic men. CARE, a secondary prevention trial, showed the benefit of treating patients with cholesterol levels within normal limits. This was confirmed by the LIPID trial, another secondary prevention study, which enrolled patients with cholesterol levels 155-271 mg/dl (4-7 mmol/l). The importance of treating patients with established ischaemic heart disease, and those at high risk of developing heart disease, regardless of cholesterol level, was being realized. In the MIRACL trial, hypocholesterolaemic therapy was useful in the setting of an acute coronary syndrome, while the AVERT study showed that aggressive statin therapy is as good as angioplasty in reducing ischaemic events in patients with stable angina. By showing the value of fluvastatin after percutaneous intervention, LIPS confirmed that benefit is a class action of the statins. The HPS randomized over 20 000 patients, and showed beyond doubt the value of statins in reducing cardiovascular events in the high-risk patient. Although PROSPER showed benefit in treating the elderly patients above 70 years, statin therapy in this trial was associated with an increase in cancer incidence. The comparative statin trials, PROVE-IT, REVERSAL, Phase Z of the A to Z, ALLIANCE and TNT, all showed that high-dose statins will better reduce cardiovascular events in the high-risk patient, although the adverse effects of therapy will also be increased. ALLHAT-LLT, ASCOT-LLA and CARDS showed that for statin therapy to demonstrate a significant benefit, hypertensive or diabetic patients must be at sufficiently high risk of cardiovascular events. The emphasis is now on the risk level for developing cardiovascular events, and treatment should target the high-risk group and not the lipid level of the patient. No therapy is free of adverse effect. Treatment of those most at risk will bring the most benefit; treatment of those not at high risk of cardiovascular disease may expose patients who would not benefit much from therapy to its adverse effects.

Adult↗
PubMed2005

Choice of antihypertensive drug in the diabetic patient.

The hypertensive patient with type 2 diabetes is especially at risk of adverse cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS) and Hypertension Optimal Treatment (HOT) studies suggested that treatment to a lower target blood pressure resulted in better prevention of clinical disease in these patients. Most trials comparing antihypertensive drugs have shown only minimal differences between the various agents. The evidence from the trials suggests that diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and the angiotensin-receptor antagonists (ARBs) will all successfully reduce adverse clinical events. The largest of the comparative hypertensive drug trials, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), demonstrated that a diuretic has a better hypotensive effect, and was more successful in preventing many aspects of cardiovascular disease compared with CCBs and ACE inhibitors. The importance of good blood pressure control and the general equivalence of antihypertensive drugs were again shown in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which compared an ARB with a CCB. Choice of antihypertensive agent should be individualized and guided by the presence of concomitant clinical disease and the need to protect any specific target organ system in the diabetic hypertensive. Diuretics, being potent hypotensive drugs with clearly demonstrated clinical benefit, should form part of the antihypertensive regimen of most diabetic hypertensives. ACE inhibitors and ARBs are especially useful in preventing nephropathy. Most patients will require a combination of antihypertensive drugs to achieve tight blood pressure control of under 130/80 mm Hg in the diabetic hypertensive. The clinician should concentrate on seeking this lower target blood pressure rather than be excessively concerned about which is the best antihypertensive agent.

Antihypertensive Agents↗
PubMed2005

A doctor's duty is to heal the unhealthy: the story of Tun Dr Mahathir Mohamad.

Mahathir Mohamad was born in 1925 in Alor Star, Kedah. He entered the King Edward VII College of Medicine in Singapore in 1947 and graduated in 1953. His years in the medical school equipped young Mahathir with the training necessary to assess and diagnose a problem, before dispensing the appropriate treatment. Throughout his later years in the political limelight, Dr Mahathir recognised the very important role the medical college had in laying the strong foundation for his successful career. He joined UMNO in 1945, already interested in politics at the tender age of 20; he was first elected into Parliament in 1964. The vigorous expression of his candid views did not go down well during the troubled days following the 13 May 1969 racial riots and he was expelled from UMNO, his writings were banned, and he was considered a racial extremist. Nevertheless, his intellectual and political influence could not be ignored for long; he returned to Parliament in 1974, and became the fourth, and longest serving, Prime Minister of Malaysia in 1981. Dr Mahathir has found fame as a Malay statesman, and an important Asian leader of the twentieth century with much written, locally and internationally, debating his policies. This article, using Dr Mahathir's own writings, starts with his description of his early life, proceeds to look at his medical career, then touches on his diagnosis of the problems plaguing the Malays, before concluding with his views on the need to stand up to the prejudices and pressures of the Western world. Throughout his life, Dr Mahathir behaved as the ever-diligent medical doctor, constantly studying the symptoms to diagnose the cause of the ills in his community and country, before proceeding to prescribe the correct treatment to restore good health. It is a measure of his integrity and intellectual capability that he did not seek to hide his failures, or cite unfinished work in an attempt to cling to political power.

Attitude↗
PubMed2004

Water Environment Research Foundation (WERF) anaerobic digestion and related processes, odour and health effects study.

Biosolids odour emissions can affect the ability of wastewater utilities to implement beneficial biosolids processing and reuse programs. Communities often become more sensitised and vocal about biosolids issues, once they experience odours emanating from a nearby site. Odour impacts from biosolids, including potential human health effects, have been targeted recently by many national and local newspapers, citizens' groups, and regulatory agencies, who have raised significant concerns, ranging from viable disposal methods/sites to outright bans. Many national and local regulatory agencies in the United States are considering biosolids disposal bans in their communities because of misinformation, poor science, and citizen pressure, but primarily because of odour impact concerns. The wastewater industry has a relatively poor understanding of the operations and treatment parameters that influence biosolids odour emissions. Thus, wastewater treatment plants are often unable to control the odour quality of the biosolids that are delivered into communities. A research study to demonstrate the influence of anaerobic digestion, mechanical dewatering, and storage design and operating parameters on the odour quality of the final product was performed and is the subject of this paper. Established and new sampling and analytical methods were used to measure biosolids odour emissions from 11 test sites in North America. By determining the impacts of these control variables on biosolids odour quality, design and operations of anaerobic digestion systems might be enhanced. This paper also summarises a corollary study performed as part of the WERF research study that addresses the health effects of biosolids odours.

Community Participation↗
PubMed2003

Pulmonary function and scoliosis in children with spinal muscular atrophy types II and III.

AIMS: The objectives were to evaluate the clinical course of spinal muscular atrophy (SMA) types II and III patients necessitating scoliosis surgery at the National University Hospital, Singapore. METHODS: A retrospective review of SMA types II and III patients, born over a 10-year period between 1983 and 1992, was conducted. RESULTS: There were eight patients: four with SMA type II and four with SMA type III. The mean age at scoliosis surgery was 9 years 7 months (range 7 years 6 months-12 years 4 months). The mean preoperative Cobb angle was 65.4 degrees (range 43-90 degrees ) and the mean postoperative Cobb angle was 22.6 degrees (range 12-45 degrees ), with a mean correction of 64.8% (range 47.7-77.8%). The decline in percentage predicted forced vital capacity (FVC) was 7.7% (95% CI: 12.4% to 3.0%) per year preoperatively and this was reduced to 3.8% (95% CI: 5.8% to 1.9%) per year postoperatively. The mean length of preoperative and postoperative lung function follow-up was 6.3 months (range 0.03-31 months) and 44 months (range 0-110 months), respectively. CONCLUSIONS: This study suggests that pulmonary function in SMA types II and III continues to decline after scoliosis surgery, though the rate of decline is less marked. Overall, the combined results from this study and all other previously published studies are conflicting in regard to the effect of scoliosis surgery on pulmonary function in SMA types II and III, though half of the studies (3 of 6) did demonstrate a continued decline in lung function postoperatively. This decline in pulmonary function despite spinal stabilization is likely secondary to the progressive neuromuscular weakness of the disease.

Adolescent↗
PubMed2002

Protecting the heart: a practical review of the statin studies.

The aim of this review of the landmark HMG-CoA reductase inhibitors (statins) studies is to enable the clinician to draw practical lessons from these trials. The Scandinavian Simvastatin Survival Study (4S) established the importance of treating the hypercholesterolemic patient with established cardiovascular heart disease. The West of Scotland Coronary Prevention Study (WOSCOPS) showed the benefit of treating healthy hypercholesterolemic men who were nevertheless at high risk of developing cardiovascular heart disease in the future. The Cholesterol and Recurrent Events (CARE) study, a secondary prevention trial, proved the benefit of treating patients with myocardial ischemia and cholesterol levels within normal limits. This conclusion was confirmed by the Long-term Intervention With Pravastatin in Ischemic Disease (LIPID) study, another secondary prevention study that enrolled patients with a wide range of cholesterol levels (4-7 mmol/dL), into which the large majority of patients would belong. The importance of treating patients with established ischemic heart disease (IHD), and those at high risk of developing cardiovascular heart disease, regardless of cholesterol level, was being realized. The Air Force/Texas Coronary Artery Prevention Study (AFCAPS/TexCAPS) then showed that treatment can reduce adverse cardiovascular events even in the primary prevention of patients with normal cholesterol levels. The Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering (MIRACL) trial showed that hypocholesterolemic therapy is useful in the setting of an acute coronary syndrome, while the Atorvastatin Versus Revascularisation Treatment (AVERT) study showed that aggressive statin therapy is as good as angioplasty in reducing ischemic cardiac events in patients with stable angina pectoris. Finally, the Heart Protection Study (HPS) randomized more than 20,000 patients, and the value of statins in reducing adverse cardiovascular events in the high-risk patient, including the elderly, women, and even in those with low cholesterol levels, is beyond doubt. The emphasis is now on the risk level for developing cardiovascular events, and treatment should target the high-risk group and not be dependent on the actual cholesterol level of the patient. It is interesting to compare the large amount of data on the value and safety of the statins with the much more limited and less convincing data on antioxidant vitamins.

Clinical Trials as Topic↗
PubMed2001

Epidemiology of West syndrome in Singapore.

The incidence of West syndrome (WS) was determined by a search of reports of electroencephalograms (EEG) recorded in 1998 and 1999 in all public hospitals in Singapore. Amongst records of patients born in 1998, nine were found with EEG features of hypsarrhythmia or modified hypsarrhythmia with onset of seizures between January 1,1998 and December 31, 1999. The medical records of these patients were reviewed. The population of children born in 1998 was 43,664. In 1998 and 1999, 67% of all hospital admissions for patients 2 years or younger in Singapore were in public hospitals. The cumulative incidence of WS in Singapore corrected for the percentage of hospital admissions to public hospitals was 3.1/10,000 live births. The corrected cumulative incidences in Chinese, Malays and Indians were 2.7, 3.1 and 3.3 per 10,000, respectively. Three cases were idiopathic; three were due to congenital structural lesions of the brain; one each had periventricular leucomalacia, intracranial hemorrhage and severe intrauterine growth retardation. None of the patients were normal at follow up. The three patients with idiopathic WS had mild global developmental delay and the other six cases had cerebral palsy and severe mental retardation. With the best modern medical treatment, possibly only two of the nine cases of WS may have been prevented.

Asian People↗
PubMed2001

The use of vigabatrin in infantile spasms in Asian children.

BACKGROUND: The use of adrenocorticotrophic hormone (ACTH) and prednisolone in the management of infantile spasms has been well established, but is associated with significant morbidity and cannot be used as long-term medication. Since the introduction of vigabatrin, results have been promising with suggestions currently that it should be used as first-line management of infantile spasms. AIM: The aim of this study was to establish the efficacy, tolerability and problems associated with the use of vigabatrin, in Asian children with infantile spasms. MATERIALS AND METHODS: Eighteen local Asian patients with infantile spasms were given vigabatrin, in 8 as first-line monotherapy and in 10 patients as add-on therapy to pre-existing anti-convulsants. RESULTS: Thirty-nine per cent (7/18) showed 100% suppression of seizures at 2 weeks and 50% (9/18) showing complete suppression of seizures at 4 weeks after starting therapy. There was however, a high relapse rate (56%) in complete responders within the first 6 months of therapy. This was probably due to a lower maintenance dose in the patients, as those who relapsed were on an average dose of 59 mg/kg/day at the time of relapse and responded to a stepped up dose of 83 mg/kg/day. Vigabatrin was well tolerated and only 2 patients developed somnolence and irritability. CONCLUSION: A dose of at least 70 mg/kg/day may be necessary to achieve adequate control and yet avoid the common adverse affects of vigabatrin.

Anticonvulsants↗
PubMed2000

Benign childhood epilepsy with centrotemporal spikes: is it always benign?

Most children with benign childhood epilepsy with centrotemporal spikes have few seizures, and some have only one. We describe two children with interictal and ictal findings consistent with this epileptic syndrome but with severe intractable seizures and cognitive decline that resulted in consideration for epilepsy surgery. Spontaneous remission occured in one child; the other is still young. Despite the high seizure burden and cognitive decline, surgical consideration should be withheld, as these seizures are likely to remit.

Brain↗
PubMed2000

Parent- and patient-validated content for pediatric epilepsy quality-of-life assessment.

PURPOSE: The purpose of this study was to assess the parent-and patient-validated content of quality-of-life measurement for use in children with epilepsy. METHODS: We asked the parents of 80 consecutive children and adolescents with epilepsy to list in order of importance their concerns about living with or caring for their children with epilepsy. Patients were 3 months to 18 years of age (mean, 10 years) and identified at the outpatient clinic or during hospital stay. To minimize investigator bias, parents and children listed their concerns in a private setting without staff involvement. RESULTS: Twenty-six distinct domains were generated by the parents and children. Concerns listed by more than 20 of parents included medication adverse effects (58), cognitive effects of epilepsy (46), prospects for the future (41), safety (35), independence (31), and brain damage caused by seizures (30). Concerns ranked by parents as most important included safety (18), brain damage from seizures (12), enigma of epilepsy (12), cognitive effects of epilepsy (11), and prospects for the future (10). Concerns listed by more than 20 of children included social problems (35), cognitive effects of epilepsy (29), driving (29), sports (27), medication adverse effects (25), and schooling (21). Concerns ranked by children as most important included issues related to medication adverse effects (13), cognitive effects of epilepsy (10), hatred of epilepsy (8), social embarrassment (6), fear of seizures (6), injury (6), and dislike of hospital visits (6). CONCLUSION: The effect of epilepsy on health-related quality of life in pediatric patients is defined by a limited number of domains. A 20-item inventory was chosen from the 26 domains generated by the parents and children. Our study provides insight into parents' and children's perception of seizures and the impact of epilepsy on everyday life.

Adolescent↗
PubMed2000

Sandhoff disease--a case report of 3 siblings and a review of potential therapies.

INTRODUCTION: Sandhoff disease is a GM2 gangliosidosis that may present within the first 6 months of life with developmental regression. This is the first report of a pedigree from Southeast Asia. CLINICAL PICTURE: All the affected siblings presented in the first year of life with developmental regression, spasticity, seizures and loss of vision. The diagnosis was confirmed by an enzymatic deficiency in both beta-hexosaminidase A and B. CONCLUSION: As the disorder is autosomal recessive, and no curative therapy is currently available, genetic counselling is necessary to prevent the burden of this devastating disease. We review the potential strategies of treatment for Sandhoff disease.

Child, Preschool↗
PubMed2000

Transaminitis in Duchenne's muscular dystrophy.

BACKGROUND: Persistently raised transaminase levels often prompt the clinician to investigate for liver pathology. Previously, some of our patients with Duchenne's muscular dystrophy have had investigations to look for liver disorders when the alanine transaminases (ALTs) were found incidentally to be high. AIM: The objective of the study was to ascertain the levels of the transaminases in patients with Duchenne's muscular dystrophy and to see if the levels of transaminases correlated with muscle enzymes such as creatine kinase (CK). MATERIALS AND METHODS: This is a case series of 19 patients with Duchenne's muscular dystrophy. Alanine and aspartate transaminase (AST) levels and CK levels were measured in the serum of the patients. RESULTS: In this series, ALT and AST levels were all found to be raised significantly in patients with biopsy-proven Duchenne's muscular dystrophy and Becker's muscular dystrophy. Alanine transaminase, in particular, was raised to a mean of 356 mmol/L, 9 times above the mean for normal. There was also good correlation between ALT and CK levels with a correlation coefficient of r = 0.80 and P value 0.01. Similar to CK, the transaminase levels were inversely proportional to mobility and to age. CONCLUSION: The presence of hypertransaminasemia in patients with muscular dystrophy should be attributed to muscle breakdown rather than to liver pathology and such patients should not be over-investigated for liver disease. In the absence of liver pathology, raised transaminases may be an early sign of occult muscular dystrophy and such patients should have CK levels checked to look for evidence of muscular dystrophy.

Alanine Transaminase↗