The three dimensions in medicine: science, art and ethics.
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Clinical Competence↗
Biomedical subjects
T C Chao
Publications and source records attributed to T C Chao.
The first fatal 2,6-di-isopropylphenol (propofol) poisoning in Singapore: a case report.
The propofol levels in the blood and tissues of a 37-year-old Chinese male suspected of having fatally self-administered an intravenous dose of 1600 mg of propofol (12.3-15.4 times the dose required for the induction of anaesthesia) were determined by headspace gas chromatography. The blood (femoral), liver, kidney and brain propofol levels were 2.5 micrograms/ml, 22 micrograms/g, 3.6 micrograms/g and 11.3 micrograms/g, respectively. The blood propofol level in the present case is 11.4 times and the liver propofol level is 15.7 times that of the first propofol overdose reported in the literature.
Adult↗
Steroid sex hormones and macrophage function: modulation of reactive oxygen intermediates and nitrite release.
PROBLEM: In general, females have a more active immune response than do males. The effects of female sex hormones on lymphocytes have been studied extensively but their effects on macrophages are poorly understood. METHOD: In this study, peritoneal macrophages (M phi) obtained from male rats were treated in vitro with estradiol (E2), progesterone (P), testosterone (TS), or hydrocortisone (HC) and their effects on superoxide, hydrogen peroxide, and nitrite release determined. RESULTS: At concentrations between 10(-10) and 10(-9) M, female and male sex hormones had no significant effect on superoxide release but, at concentrations above or below that range, these hormones stimulated the release of these reactive oxygen intermediates (ROI). In contrast, M phi treated with HC generally exhibited either unaltered or reduced ROI release. CONCLUSIONS: These findings suggest that female sex hormones regulate ROI release by M phi in a manner not entirely shared by other steroid hormones. At most concentrations used, E2, P, TS, and HC significantly inhibited nitrite release by M phi. However, with 10(-10) M of E2 or 10(-9)M of P, nitrite release by M phi was not affected. In the presence of anti-TNF antibody, the amounts of superoxide and hydrogen peroxide release were moderately reduced but nitrite release was dramatically inhibited. The sensitivity of M phi to variations in the concentrations of female sex hormones may contribute to gender-related differences in the immune response.
Animals↗
Aflatoxin exposure in Singapore: blood aflatoxin levels in normal subjects, hepatitis B virus carriers and primary hepatocellular carcinoma patients.
Blood screening conducted on Singaporeans over 1991-1992 showed exposure to predominantly aflatoxin B1 and to a lesser extent G1. The extent of exposure to B1 among three groups of residents in Singapore, namely normal subjects (n = 423), hepatitis B virus carriers (n = 302) and primary hepatocellular carcinoma (PHC) patients (n = 58) were extensive as reflected by the positive rates of 15.1, 0.7 and 1.7 per cent respectively. However, the degree of individual exposure to this toxin among the three groups was considered low as shown by the low respective mean blood levels of 5.4 +/- 3.2 (range 3.0-17), 7.7 (range 7.5-7.9) and 7.5 picogrammes per ml of blood. It is not immediately clear whether or not such low levels would precipitate an undesirable health effect. The higher positive rate seen in normal subjects as compared with the other groups could be due to differences in dietary intake of aflatoxin B1, differences in metabolic patterns or both. About 70 per cent of PHC patients studied were carriers. The degree of aflatoxin B1 exposure among normal subjects in Singapore was a factor of 22.1 times less than that in Japan, 40.9 times less than that in Indonesia and 51.3 times less than that in the Philippines. Similarly, the extent of exposure among hepatitis B carriers in Singapore was a factor of 8.2 times, 39.6 times and 24.2 times less than those in the other three Asiatic countries respectively. The results reflected stringent Government control over the quality of food stuff imported into this country. As Singapore imports almost all of its dietary needs from elsewhere, it can afford to be selective at a cost. Aflatoxin M1, a metabolite of B1, was most commonly encountered in the liver tissues of deceased (n = 154) who died of causes other than sickness or disease in 1992-93, consistent with our blood findings of prevalence of aflatoxin B1. High performance liquid chromatography (HPLC) with fluorescence detection using one of the aflatoxins G2 or B2 as an internal standard was used for the detection and quantification of aflatoxins. The use of an internal standard structurally and chemically similar to those required to be quantified minimizes errors in quantifications. This is because differences in the quenching of fluorescence between specimen extracts and spiked-standard extracts were internally standardized and compensated for. The presence of an internal standard also helped to locate aflatoxins of interest more accurately.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Age-related changes in normal Chinese hearts.
The heart weights, ventricular wall thickness and valve circumferences were measured in 507 autopsy specimens of normal hearts from persons aged from 10 to 90 years. The heart weights increased with age and were greater in the males than in the females, except from the 6th to 8th decades where they were reversed. The body weight was the best predictor of heart weight. The ventricular wall thickness in males did not differ significantly from that in females. The values of the indexed left ventricular wall thickness (i.e. values divided by BSA) in the females exceeded those in the males from the 6th to 9th decades. The mean valve circumference was greater in the males but it was significant (P < 0.05) only for the tricuspid valves at the 9th decade of life. The pulmonary valve circumferences were greater than the aortic for all decades and the ratio of the aortic to pulmonary valve circumference remained constant. In the clinical evaluation of the specimens of Chinese hearts, the absence of the aged-related dilatation of the aorta described in Caucasian hearts should be duly taken into account.
Adolescent↗
Localization of sarcoma xenografts in nude mice with indium-111-labeled monoclonal antibodies.
A labeling method utilizing modified carbohydrate moieties in antibody heavy chains as radionucleotide binding sites was evaluated. Murine anti-sarcoma monoclonal antibody (MAb 19-24) was labeled with Indium-111 (111In) using this technique and subcutaneous human sarcoma xenografts were successfully localized in nude mice. A nonspecific monoclonal antibody BL-3 was used as a negative control. Tumor-to-blood ratios of radioactivity in the mice injected with 111In-labeled MAb 19-24 were significantly (P < 0.05) higher than those obtained with nonspecific MAb BL-3. Calculations of percentage injected dose of radioactivity per gram tissue showed relatively high specific uptake of MAb 19-24 in sarcoma xenografts. Radioactivity cleared from the blood rapidly and hepatic uptake of 111In-labeled antibodies was found to be relatively low. Biodistribution studies in normal mice with 111In-labeled antibodies showed only blood pool activity with no significant concentration of activity into organs. Therefore, immunoreactivity of the antibodies was retained after 111In-labeling utilizing this new technique, allowing specific binding of radiolabeled MAb to tumor xenografts with relatively low hepatic uptake.
Animals↗
Epidemiology of sudden unexpected death syndrome among Thai migrant workers in Singapore.
A total of 235 cases of sudden unexpected death syndrome (SUDS) among apparently healthy male Thai migrant workers in Singapore were reported between 1982 and 1990. Most of the deaths occurred during sleep and 13% were not sleep-related. The median age at the time of death was 33 years and the median interval between arrival and death was 8 months. These deaths occurred singly and sporadically throughout the year. Post-mortem examination revealed few abnormal findings except for haemorrhagic congestion or oedema of the lungs. There were moderate to severe intra-alveolar haemorrhages with some evidence of myocarditis or pneumonitis. Preliminary findings of serial sections of the hearts indicate evidence of anomalies in the cardiac conduction system. Epidemiological investigations showed that a family history of similar deaths and serological evidence of current or recent infection with Pseudomonas pseudomallei were significantly associated with SUDS. Extensive biochemical and toxicological investigations were inconclusive. There was no evidence of chronic deficiency in thiamine or potassium among the healthy Thai workers living and working in the same conditions as the cases, and no significant abnormalities were detected on electrocardiographic examination. As these migrant workers experienced various psychosocial problems which could stem from maladjustment to an urban environment, separation from the family, burden of debts and long hours of work, stress could be a precipitating factor for SUDS.
Adult↗
Relationship between postmortem blood and vitreous humor ethanol levels.
The relationship between the blood to vitreous humor ethanol ratios (B/V) and the corresponding urine to blood ethanol ratios (U/B) of 200 postmortem cases were found to be bimodal in nature. Using the U/B ratio of 1.20 as a demarcation below which early absorption prevails, the results in the early absorption phase gave an average B/V ratio of 1.29, a range from 0.71 to 3.71, and a relatively large standard deviation of 0.57, whereas the results in the other phases (late absorption and elimination) gave an average B/V ratio of 0.89, a spread from 0.32 to 1.28, and a standard deviation of 0.19. It would appear that the blood ethanol levels can be estimated using B = 1.29 V for early absorption phase cases and B = 0.89 V for cases in subsequent phases. The former relationship would underestimate the blood ethanol levels in cases of very early absorption phase and the later overestimate the levels of late elimination cases. The ethanol distribution results in cases of fatal road traffic accidents and suicides by falling, in which 69% of the deceased sustained some form of head injury, were found to be similar to those of other postmortem cases. The observations reflect that vitreous humor, being reasonably protected, is likely to survive certain traumatic deaths and be available for postmortem ethanol investigation. The U/B ethanol ratios recorded in this work had an average of 1.29, a range from 0.19 to 5.19, and a standard deviation of 0.48.
Accidents, Traffic↗
Glue sniffing deaths in Singapore--volatile aromatic hydrocarbons in post-mortem blood by headspace gas chromatography.
Over a period from 1983 to 1991, of a total of 19,000 post-mortems, 33 were found to have at least one aromatic hydrocarbon (benzene, toluene or xylenes) in the blood. Of the 33 deceased, 22 had a history of toluene or petrol abuse while most of the remaining 11 were suspected to be glue sniffers through evidence found at the scene. This number, which represented 0.17 per cent of all the unnatural deaths, is considered small for a nation having a glue sniffing epidemic. The low death rate, as compared to 2.1 per cent through drug and chemical poisoning during the same period, is attributed to the timely intervention by the Government who outlawed glue sniffing and the effectiveness of compulsory rehabilitation. The male gender predominates (81.8 per cent) among the 33 deceased with a mean age of 20.1 years (range 15 to 33). The mean age for the female gender is 17.7 years (range 16 to 20). The blood toluene levels were found to be in the range 0.2 to 92 micrograms per ml blood. The causes of death are: 63.6 per cent due to falling or suicide by jumping; 18.2 per cent drowning; 6.1 per cent hanging; 6.1 per cent homicide; and 6.1 per cent acute toluene poisoning. The high proportion of traumatic deaths are discussed. Headspace gas chromatography with a suitable GC column was used for the analysis. Calibration blood standards were prepared in situ or in bulk stabilized by 10 per cent (v/v) methanol to overcome the hydrophobic and volatile nature of the aromatic hydrocarbons.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Poisons information in Singapore.
The Poisons Information Centre (PIC) provides viral and timely information to prevent and manage poisoning episodes. Comprehensive information on household, agricultural and industrial chemicals, natural toxins, pharmaceuticals, local antidote stocks and local poisons experts is retrieved from the Centre's computerised information system and printed literature. Public subscribers can obtain poisons information through Teleview.
Adult↗
Legal medicine.
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Coroners and Medical Examiners↗
Toxicology Services in Singapore.
The toxicology laboratory provides a whole range of forensic toxicology services to the doctors, pathologists, law enforcement agencies and the public. This paper, anchored in one hundred and ten years of history, traces the practice and development of this laboratory to the present day of offering services in blood for alcohol determinations, antemortem biological fluids (gastric aspirate, blood, etc.) and postmortem biological fluids and tissues (liver, kidney, etc.) for drugs and poisons screen. This paper spells out in detail the nature of specimens required, the analytical techniques used, the toxins looked for and the medico-legal implications of our analytical findings. A number of recent cases of interest are presented.
Body Fluids↗
Adverse drug reactions--tales of a forensic pathologist.
Drugs can produce adverse reactions in susceptible patients. This can range from minor discomfort to major morbidity or even death. The pharmacological properties of certain drugs have a high potential in producing these adverse reactions, especially if large doses are given or given simultaneously with interacting drugs or given in the presence of renal or liver dysfunction of the patient. Clinicians should be aware of the potential toxicity of the drugs they prescribe and their interacting drugs. In Singapore, deaths due to adverse drug reaction are regarded as unnatural deaths and they should be reported to the Coroner. These cases are usually subjected to a post-mortem examination. Clinicians are not allowed to sign up cases of death due to adverse drug reactions and those who do so will be subjected to queries from the Registrar of Death and the Coroner. Every year doctors have been called up to explain their misdeeds and warned. Fortunately there are not many such cases. Some cases of deaths due to adverse reactions to tetracyclines, sulphur, phenylbutazone, penicillin, paracetamol, etc will be discussed.
Adolescent↗
Toxicological screen on gastric aspirates: the Singapore experience.
In the early eighties, in response to increasing self-poisoning incidents by pharmaceuticals in Singapore, a comprehensive wide-sweep screen for these drugs in clinical gastric aspirates was devised and implemented by us. The toxicological screen which involved quadruplicate extractions, two in acidic conditions and the other two in alkaline conditions, required the following analyses to be carried out: UV on the acidic fraction, TLC on the basic fraction and mega-bore capillary GC/NPD (nitrogen phosphorus detector) on the combined fraction. The combined fraction if necessary was subjected to GC/MS analysis. Our screen satisfied the need to confirm the analytical outcome of one method by another. Combining the acidic and basic fractions for a single GC analysis saves on instrument time and manpower. All coma and emergency cases were required to undergo GC/MS analysis to prove the identity of toxic agents beyond reasonable doubt. Quality control procedures were instituted at key steps to ensure quality of analytical outcome.
Calibration↗
Drinking and driving in Singapore, 1987 to 1989.
Between 1987 and 1989 there were approximately 5,000 cases of fatal and injury-sustained road traffic accidents, of which 2.3-3.0% were alcohol related (blood alcohol levels greater than the legal limit of 80 mg% ethanol). The offenders of alcohol-related accidents are mostly Chinese (> 79%), male (> 98%), and more often 30-40 years old. The majority of the alcohol-related accidents (> 74%) took place between 8 P.M. and 4 A.M. in fine weather and light traffic. Rear-end, head-on, and side-on collisions comprised > 60% of all the alcohol-related accidents, and losing control of vehicles approximately 30%. Drunken driving cases for the same period that were not accidents showed a number of characteristics similar to those for accidents. In Singapore, motorcycle riders and pedestrians are more prone to road fatality than other road-user groups. International comparisons of road fatalities per 100,000 population gave Singapore one of the lowest accident rates (8.1-8.4) as compared with countries such as Australia, the United Kingdom, the United States, New Zealand, Canada, and Japan.
Accidents, Traffic↗
Common poisons in Singapore--past and present.
A study on past toxicological activities in Singapore enabled us to capture the trends of poisons abused in this country over the last 108 years. Until the early sixties, corrosive alkali and acids, alcohol (poisoning cases), inorganic chemicals, heavy metals and plant alkaloids were the mainstay of poisons principally used. The seventies and eighties saw a swing towards pharmaceuticals. The 1988-89 data gave alcohol (poisoning cases), pharmaceuticals, household items such as detergents, hypochlorite and antiseptic, carbon monoxide, paraquat, malathion, organic solvents (toluene and xylenes) and narcotics as the mainstay of poisons encountered. The last two classes of poisons reflect the continuing problems of glue sniffing and narcotics abuse facing Singapore.
Adult↗
Forensic investigation of deaths due to fire in mass disaster.
When a body is recovered from a fire site, it is essential to determine if death occurred before or after the fire started. Foul play is suspected when there is an alternative cause of death not due to the fire. In cases of mass disaster due to fire, the forensic pathologist has an additional task of identifying the bodies. This is important in medico-legal investigations. The severity of the burnt injuries sustained may be useful in the reconstruction of the incidence. Examples will be given in this paper on the identification of the burnt victims and the forensic investigations on death by fire in mass disasters.
Accidents, Occupational↗
Drinking and driving in Singapore 1987 to 1989.
In the period 1987 to 1989 there were about 5,000 cases of fatal and injury-sustained road traffic accidents, of which 2.3 to 3.0% were alcohol-related (Blood alcohol levels greater than the legal limit of 80 mg % ethanol). The offenders of alcohol-related accidents are mostly Chinese (greater than 79%), predominantly of the male gender (greater than 98%), and more often than not in the 30 to 40 age-range. The majority of the alcohol-related accidents took place between 8 p.m. to 4 a.m. (greater than 74%) under fine weather and light traffic. Rear-end, head-on and side-on collisions comprised over 60% of all the alcohol-related accidents and losing control of vehicles about 30%. Drunken driving non-accident cases for the same period showed a number of characteristics similar to those for alcohol-related accident cases. In Singapore motorcycle riders and pedestrians are more prone to road fatality than other road-user groups. International comparisons of road fatalities per 100,000 population gave Singapore one of the lowest accident rates (8.1 to 8.4) as compared to countries such as Australia, the United Kingdom, the United States, New Zealand, Canada and Japan.
Accidents, Traffic↗