Relationships between cigarette smoking, blood pressure and serum lipids in the Singapore general population.

In a cross-sectional random survey of the whole of Singapore (2143 subjects aged 18-69 years), cardiovascular risk factors were measured by standardized techniques. For the analysis in the 18-69 year age group there was adjustment for ethnic group, age, body mass index, alcohol consumption and physical activity. Among serum lipids, high density lipoprotein (HDL-) cholesterol and fasting triglyceride were inversely related with partial correlation coefficients (r) of males -0.34 (P < 0.001) and females -0.26 (P < 0.001). There were no relationships between blood pressure and serum lipids except for direct ones with fasting triglyceride, being males (systolic r = 0.06, P = 0.066 and diastolic r = 0.12, P < 0.001) and females (systolic r = 0.11, P < 0.001 and diastolic r = 0.13, P < 0.001). Cigarette smoking, in males, was related to systolic blood pressure (inversely), with, compared to non-smokers, a reduction of 1.3 mm Hg (1.1%) in light smokers, 3.8 mm Hg (3.1%) in moderate smokers and 4.6 mm Hg (3.7%) in heavy smokers; there was no clear relation with diastolic blood pressure. Cigarette smoking, in males, was related to HDL-cholesterol (inversely), even after further adjustment for fasting triglyceride, with compared to non-smokers reductions of 0.03 mmol/l (3.4%) in light smokers, 0.09 mmol/l (10.3%) in moderate smokers and 0.12 mmol/l (13.8%) in heavy smokers. Cigarette smoking was related to fasting triglyceride (directly) but this was removed by further adjustment for HDL-cholesterol. Cigarette smoking was not related to low density lipoprotein cholesterol. These results are compared to those of other surveys.

A comparative study of the maximum oxygen uptake of regularly exercising and non-exercising health adult men in sedentary occupations.

This study aims to assess and compare the aerobic fitness (max VO2) of 210 healthy adult men in sedentary occupations in Singapore. All the subjects studied were in codes 0 to 2 of the Singapore Standard Occupational Classification, comprising professional, technical, administrative and related workers. Their max VO2 were determined from direct analyses of their expired respiratory gases during an all-out run on a treadmill. Of these 210 men, 71 (33.8 per cent) were recreation-related regular exercisers and their mean max VO2 of 40.9 ml/kg per min STPD (at standard temperature and pressure, dry) and 95 per cent confidence interval of 39.2-42.6 ml/kg per min was significantly higher (p less than 0.001) than that of the remaining 139 men (34.3 ml/kg per min STPD) with 95 per cent confidence intervals of 33.2-35.4 ml/kg per min who were not regular exercisers. The regular exercisers also met the max VO2 requirements for heavy physical work capacity and compared favourably with the recommended standards for aerobic fitness in the National Physical Fitness Award of Singapore as well as Cooper's Standards based on North American men while the non-regular exercisers did not. The study has shown that the recreation-related regular exercise of the study-defined type, intensity, duration and frequency can significantly improve the physical work capacity of healthy adult men in sedentary occupations in Singapore.

Corneal arcus and cardiovascular risk factors in Asians in Singapore.

This study was a cross-sectional random survey of the whole of Singapore, based on 2143 subjects (aged 18-69 years, response rate 60.3%). The presence of corneal arcus was determined by a doctor using the naked eye in good light. Cardiovascular risk factors were measured by standardized techniques. The prevalence rates overall of corneal arcus were: 18-29 years (males 0.5%, females 0.3%), 30-49 years (males 18.1%, females 13.3%) and 50-69 years (males 70.7%, females 55.3%). In the 30-49 age group, people with arcus had higher serum low density lipoprotein (LDL) cholesterol concentrations than people without arcus, the mean differences being, males 0.31 mmol/l (P = 0.040) and females 0.62 mmol/l (P less than 0.001) with an increased likelihood of having values greater than 5.5.mmol/l of males 1.8 (95% confidence interval (95% CI): 1.0-3.4) and females 2.6 (95% CI: 1.4-4.8). There were no significant differences for LDL-cholesterol in the 50-69 age group. Arcus was weakly associated with fasting plasma glucose in the 30-49 age group. Arcus was not associated with serum high density lipoprotein (HDL) cholesterol, serum fasting triglyceride, blood pressure and cigarette smoking. It is concluded that while corneal arcus is primarily an age-related change, its formation is accelerated by high serum LDL-cholesterol so that in people under 50 years it is a marker for the condition.

Cardiovascular diseases in Chinese, Malays, and Indians in Singapore. II. Differences in risk factor levels.

STUDY OBJECTIVE: The aim of the study was to examine cardiovascular risk factors to see how these might explain differences in cardiovascular disease mortality among Chinese, Malays, and Indians in the Republic of Singapore. DESIGN: The study was a population based cross sectional survey. Stratified systematic sampling of census districts, reticulated units, and houses was used. The proportions of Malay and Indian households were increased to improve statistical efficiency, since about 75% of the population is Chinese. SETTING: Subjects were recruited from all parts of the Republic of Singapore. SUBJECTS: 2143 subjects aged 18 to 69 years were recruited (representing 60.3% of persons approached). There were no differences in response rate between the sexes and ethnic groups. MEASUREMENTS AND MAIN RESULTS: Data on cardiovascular risk factors were collected by questionnaire. Measurements were made of blood pressure, serum cholesterol, low and high density lipoprotein cholesterol, fasting triglycerides and plasma glucose. In males the age adjusted cigarette smoking rate was higher in Malays (53.3%) than in Chinese (37.4%) or Indians (44.5%). In both sexes, Malays had higher age adjusted mean systolic blood pressure: males 124.6 mm Hg v 121.2 mm Hg (Chinese) and 121.2 mm Hg (Indians); females 122.8 mm Hg v 117.3 mm Hg (Chinese) and 118.4 mm Hg (Indians). Serum cholesterol, low density lipoprotein cholesterol and triglyceride showed no ethnic differences. Mean high density lipoprotein cholesterol in males (age adjusted) was lower in Indians (0.69 mmol/litre) than in Chinese (0.87 mmol/litre) and Malays (0.82 mmol/litre); in females the mean value of 0.95 mmol/litre in Indians was lower than in Chinese (1.05 mmol/litre) and Malays (1.03 mmol/litre). Rank prevalence of diabetes for males was Indians (highest), Malays and then Chinese; for females it was Malays, Indians, Chinese. CONCLUSIONS: The higher mortality from ischaemic heart disease found in Indians in Singapore cannot be explained by the major risk factors of cigarette smoking, blood pressure and serum cholesterol; lower high density lipoprotein cholesterol and higher rates of diabetes may be part of the explanation. The higher systolic blood pressures in Malays may explain their higher hypertensive disease mortality.

Activation of bovine prothrombin as monitored by the clotting assay.

The activation of bovine prothrombin was studied with highly purified clotting factors and using a coagulation assay developed to look at the initial rate of prothrombin conversion as well as the conversion rate over a time course of 75 min. Activation of prothrombin by factor Xa alone was slow. The rate of prothrombin conversion increased markedly with the addition of each of the accessory components Ca2+, phospholipid and bovine factor V, respectively. With the complete prothrombinase complex comprising factor Xa, Ca2+, phospholipid and factor V, the rate increase was about 22,000-fold higher compared to the action of factor Xa and Ca2+ on prothrombin alone. The rates of thrombin formation obtained with activated factor X1 were only about 70% the values obtained with factor X2. The rate of prothrombin activation and the difference between the activities of the activated factors X1 and X2 are discussed.

Ischaemic heart disease and its risk factors in Singapore in comparison with other countries.

Mortality from ischaemic heart disease in Singapore is now reaching comparability with the West. For the early 1980s, rates for Indians and Malays were higher than in U.S.A. and England and Wales and while those for Chinese were lower they were considerably higher than in Japan. In keeping with this the levels of the major risk factors in Singapore are now comparable to the West. Cigarette smoking in males is virtually the same as in Britain, while the proportion of hypertensives on medication is higher than in the West. The main cause for concern is the current high levels of serum cholesterol in Singapore and strenuous health education efforts are needed to bring about dietary changes.

Lactate production in type B hyperlactataemia due to infective encephalopathy.

We have suggested that the neuroglycopenia of infective encephalopathy results in increased lactate production in muscle as an alternative cerebral fuel. Two probable mechanisms for enhanced lactate production in infective encephalopathy are fatty acidaemia and increased LDH activity. Hyperglycaemia-producing infusions should then result in clinical and metabolic recovery. Twenty-two children with encepahlopathy were studied over 2 1/2 week periods. There was normoglycaemia at admission together with hyperlactataemia (p less than 0.004), fatty acidaemia (p less than 0.004) and increased serum LDH activity (p less than 0.005). Therapeutic hyperglycaemia resulted in recovery and a progressive return of metabolic aberrations to normality. Two case reports detail the responses to such management.

Role of glucose homeostatic mechanisms in viral infections.

Though normoglycaemia is thought to indicate adequacy of cellular glucose content, ketoacidosis occurs in viral infections even in the presence of normo- and hyperglycaemia. These wide variations in glucose concentrations may reflect the patients' adaptive abilities in situations where glucose transport is impaired by viruses. Hypoglycaemia would suggest poor adaptation and hyperglycaemia good adaptation. Increased free fatty acid (FFA) concentrations and enzyme activity are probable adaptive mechanisms. If so, they should decrease with hyperglycaemia-producing infusions. Profiles of glucose, FFA, enzymes, and fever over 19 days in 24 children with viral infections are reported. On admission 87.5% were normo- or hyperglycaemic with increased FFA, AST, LDH, and fever (P less than 0.005) when compared with values 19 days later. With infusions that produced hyperglycaemia, there was clinical recovery with a decrease in FFA and enzyme activity. The hyperglycaemia observed in 56.5% therefore points to glucose homeostatic mechanisms being geared to maintain the intracellular milieu. Hence normoglycaemia does not always indicate cellular glucose adequacy.

The significance of type B hyperlactataemia in infective encephalopathy.

A disordered sensorium, a cardinal sign of lactic acidosis, is commonly attributed to the acidosis resulting from increased production and decreased utilization of lactate. We report hyperlactataemia in 22 children with encephalopathy following viral, rickettsial and bacterial infections. On admission there was normoglycaemia together with anion gap acidosis (p less than 0.02), hyperlactataemia (p less than 0.003), fatty acidaemia (p less than 0.004) and increased serum creatinine (p less than 0.0004) when compared to the results in convalescence. Management with two types of hyperglycaemia-producing infusions, one of them containing lactate, resulted in hyperglycaemia (p less than 0.002) from the 2nd to 4th days of admission. This was associated with a decrease in lactate, creatinine and acidosis and with clinical recovery. Infusions of either glucose or lactate would normally result in hyperlactataemia, more so if there was difficulty with lactate utilization. The fall in lactate supports the hypothesis that the hyperlactataemia is probably due to an adaptive increase in lactate production as an alternative cerebral fuel which is consequent on poor glucose utilization by brain, the cause of the encephalopathy. Additionally it leads to increased Cori cycle activity. Hence the clinical and metabolic recovery with such management.

Carbohydrate and lipid metabolism during human labor: free fatty acids, glucose, insulin, and lactic acid metabolism during normal and oxytocin-induced labor for postmaturity.

This investigation was performed to study the metabolism of the major body fuels (viz. glucose and free fatty acids), insulin, and lactic acid during the stress of human labor. In addition, the role of the normal placenta in the transport of these substances between mother and the fetus was evaluated by measuring them in the mother and cord blood at delivery. To study possible alterations of this role in the placenta which had exceeded the normal period of gestation, a second comparable group of women had labor induced with oxytocin 16-18 days beyond the expected date of delivery. A dramatic twofold increase in maternal plasma free fatty acids was observed during labor. There was a lesser but definite increase in blood glucose concentrations. No rise in serum insulin levels was noted which coincided with the changes in blood glucose. Lactic acid concentrations during the course of labor were variable from baseline but at delivery, the concentrations rose to very significant levels. Free fatty acids and blood glucose levels were significantly higher in the maternal than in the fetal side. A significantly positive correlation was noted between the maternal and cord blood values except for free fatty acids in the postmature group. No significant difference, nor a correlation was found between the two compartments in the insulin nor lactic acid levels. These results suggest that during human labor free fatty acids are the principal metabolic fuel. This increase in maternal free fatty acids may serve to spare glucose as a metabolic fuel in the fetus. The mechanism responsible for the increase maternal free fatty acid mobilization remains to be determined. It is not possible to discern any consistant alteration in placental function as a consequence of prolonged gestation.

Role of adipose tissue in free fatty acid metabolism in hemorrhagic hypotension and shock.

This study was designed to observe the effects of hemmorrhage on the mobilization of free fatty acids from adipose tissue under a variety of experimental conditions. Experiments were conducted in fasting rabbits and dogs. A significant fall in arterial plasma free fatty acids was observed in rabbits following hemorrhage of 4 ml every 2 min and after inducing acute hemmorrhaged to a mean arterial blood pressure of 40 mm mercury. Adipose-tissue free fatty acids and arterial-plasma free fatty acids were simulatneously measured before and after hemorrhagic hypotension until death. Afterial free fatty acids fell significantly following hemorrhage, while the concentration of adipose-tissue free fatty acids rose significantly. In the next series of experiiments, dogs were pretreated with an alpha-receptor blocking agent phenoxybenzamine and acutely hemorrhaged. The results showed a significant rise in arterial free fatty acids concentration and an insignificant increase in adipose-tissue free fatty acids. These results suggest that hypoperfusion of adipose tissue plays an important role in the decreased supply of a major body fuel following hemorrhagic hypotension. The results are compatible with the view that metabolic fuel failure may be an important factor in the development of the complications of acute hemorrhage and suggest the concept that adipose tissue may be an important target organ in hemorrhagic shock.

Studies on flavonoid metabolism. Biliary and urinary excretion of metabolites of (+)-(U- 14 C)catechin.

1. The biliary and urinary excretion of (+)-[U-(14)C]catechin was studied in normal male rats after a single injection of the flavonoid. 2. In rats large amounts of radioactivity (33.6-44.3% of the dose in 24h) were excreted in the bile as two glucuronide conjugates [one of which was a (+)-catechin conjugate] and three other unconjugated metabolites. 3. Excretion of radioactivity in the urine when the bile duct was not cannulated amounted to 44.5% of the dose. 4. In both the urine and bile the new metabolites showed maximum excretion in the (1/2)-1(1/2)h after intravenous injection of [(14)C]catechin. 5. The metabolites m-hydroxyphenylpropionic acid, p-hydroxyphenylpropionic acid, delta-(3-hydroxyphenyl)-gamma-valerolactone and delta-(3,4-dihydroxyphenyl)-gamma-valerolactione originate from the action of the intestinal micro-organisms on the biliary-excreted metabolites of (+)-catechin. These phenolic acid and lactone metabolites are then reabsorped and excreted in the urine. 6. It is proposed that, depending on the route of administration of (+)-catechin, there exists an alternative pathway, involving biliary excretion, for the metabolism of (+)-catechin.