Search

Spermatogenesis requires progression of germ line stem cells through a precisely ordered differentiation pathway to form spermatozoa. Diverse and dynamic signals from the transforming growth factor-beta (TGF-beta) superfamily influence many stages of germ cell development. For example, interactions between several TGF-beta superfamily ligands (bone morphogenetic proteins, activin, and glial-derived neurotrophic growth factor [GDNF]) appear to govern the onset of spermatogenesis, and we are exploring how germ cells interpret these competing signals. We examined the in vivo impact of activin on testis development using two mouse models, the inhba-/- mouse (which lacks the gene encoding the activin A subunit and dies at birth) and BK mice, with inhbb (encoding the activin betaB subunit) replacing inhba (which survive to adulthood and show delayed fertility onset in males). Distinct effects on Sertoli cell and germ cell populations during fetal and early postnatal development were measured. We recognize that specific proteins, including downstream targets of TGF-beta signals, such as Smads, must move into the nucleus to implement the gene transcription changes required for development. We hypothesized that changes at the level of cellular nuclear transport machinery may be required to mediate this. Examination of proteins involved in classical nuclear import, the importins, revealed that each importin has a developmentally regulated expression pattern in male germ cells. Because each importin binds a selected range of cargo proteins and mediates their nucleocytoplasmic passage, our findings suggest that each importin ferries cargo required for discrete stages of spermatogenesis.

Objective: To determine the extent of secondary prevention of coronary heart disease (CHD) and cerebrovascular disease (CVD) in low- and middle-income countries., Methods: A descriptive cross-sectional survey of a sample of 10 000 CHD (85.2%) and CVD (14.8%) patients (6252 men; 3748 women) was conducted over 6 months in geographically defined areas. The mean age was 59.2 years (standard deviation (SD), 10.8). Consecutive patients were recruited from a stratified random sample of primary, secondary and tertiary care facilities in defined areas in 10 countries (Brazil, Egypt, India, Indonesia, Islamic Republic of Iran, Pakistan, Russian Federation, Sri Lanka, Tunisia and Turkey). The main outcome measures were levels of lifestyle and physiological risk factors, and the use of drugs for secondary prevention of CHD and CVD., Findings: Approximately 82%, 89% and 77% of patients were aware of the cardiovascular benefits of quitting smoking, a heart-healthy diet and regular physical activity, respectively. About half (52.5%) engaged in less than 30 minutes of physical activity per day, 35% did not follow a heart-healthy diet and 12.5 % were current tobacco users. Blood pressure had been measured in 93.8% (range 71-100%), blood cholesterol in 85.5% (range 29-97%) and blood sugar in 75.5% (range 65-99%) in the preceding 12 months. The proportions who had received medications among CHD and CVD patients were: aspirin, 81.2%, 70.6%; beta-blockers, 48.1%, 22.8%; angiotensin-converting enzyme inhibitor, 39.8%, 37.8%; statins, 29.8%, 14.1%, respectively. About one-fifth of patients with CHD had undergone revascularization., Conclusion: A significant proportion of patients did not receive appropriate medications. About 47% of patients had at least two or more modifiable risk factors (smoking, physical inactivity, hypertension, diabetes or hypercholesterolaemia). There are considerable missed opportunities for prevention of recurrences in those with established CVD in low- and middle-income countries.

Objective: To determine the prevalence of selected cardiovascular risk factors in adult Sri Lankan population in four provinces., Design: Cross-sectional, based on a stratified cluster sampling method., Settings: Four provinces, namely the Western, North Central, Southern and Uva., Patients: Six thousand and forty seven participants (2692 men) between the age of 30 and 65 years were surveyed., Measurements: Risk factors measured included height, weight, waist and hip circumference. Waist to hip ratio and body mass index were calculated, and overweight (23 kg/m2) and obesity (> or = 25 kg/m2) determined. Hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg or use of anti-hypertensive medications), and diabetes mellitus (fasting serum plasma glucose level > or = 7 mmol/L or use of anti-diabetic medications) and impaired fasting glycaemia (> or = 6.1 to < 7 mmol/L) were also determined., Results: The prevalence of hypertension as defined was 18.8% (CI 14.5-23.1) for men and 19.3% (CI 12.2-26.4) for women. The prevalence of diabetes was 14.2% (CI 11.9-16.5) for men and 13.5% (CI 6.9-20.1) for women while impaired fasting glycaemia was 14.2% for men and 14.1% for women. The mean body mass index was 21.5 kg/m2 (SD = 3.7) in men. It was lower than that in women, 23.3 kg/m2 (SD = 4.5). The prevalence of obesity was 20.3% in men and 36.5 % in women. Regional differences were seen in the mean fasting blood glucose and prevalence of diabetes, and mean BMI and prevalence of obesity were highest in Western province. Mean blood pressure and prevalence of hypertension were highest in the Uva Province. Southern Province had the lowest prevalence of hypertension and diabetes, and North Central Province had lowest anthropometric measures of obesity., Conclusions: The prevalence of the selected cardiovascular risk factors is common in the adult Sri Lankan population surveyed. Regional differences exist in the prevalence of these risk factors. The prevalence of high level of risk factors requires urgent public health action.

This paper, which summarizes the conclusions of a WHO Expert meeting, is aimed at proposing indications to develop technical specifications for an accurate and affordable blood pressure measuring device for office/clinic use in low resource settings. Blood pressure measuring devices to be used in low resource settings should be accurate, affordable, and easily available worldwide. Given the serious inherent inaccuracy of the auscultatory technique, validated and affordable electronic devices, that have the option to select manual readings, seem to be a suitable solution for low resource settings. The agreement on the technical specifications for automated blood pressure measuring devices for office/clinic use in low resource settings included the following features: high accuracy, adoption of electronic transducers and solar batteries for power supply, standard rates of cuff inflation and deflation, adequate cuff size, digital display powered by solar batteries, facilities for adequate calibration, environmental requirements, no need of memory function, resistance to shock and temperature changes, and low cost. Availability of a device with these features should be accompanied by adequate training of health care personnel, who should guarantee implementation of the procedures recommended in recent European and American Guidelines for accurate blood pressure measurement.

Causes of the burgeoning cardiovascular epidemic in developing countries (DC) are known. Whilst there are many prevention strategies and policies demonstrated to be effective in reducing the trends of cardiovascular disease in developed countries, applying them in DCs is challenging and complex. To utilize resources efficiently, two key decisions have to be made by policy makers in all DCs. The first is to decide on the appropriate mix of population and high-risk interventions. The second is to determine the threshold for implementing high-risk interventions. In making such decisions, due consideration needs to be given to scientific evidence, affordability, sustainability, opportunity costs, and social and political realities. High-risk approaches can be made cost-effective if individuals that are most likely to benefit from treatment can be identified through risk stratification systems. Although several such risk prediction systems are available, they have limited applicability to non-Western populations. Further, health systems in DCs do not have basic infrastructure facilities to support resource intensive risk prediction tools, particularly in primary healthcare. The World Health Organization has developed a flexible cardiovascular disease risk management package that is implemented in a range of less resourced settings. A risk prediction tool that enables more accurate prediction of cardiovascular risk in DCs is in development.

Objective: Assess capacity of health-care facilities in a low-resource setting to implement the absolute risk approach for assessment of cardiovascular risk in hypertensive patients and effective management of hypertension., Design and Setting: A descriptive cross-sectional study in Egbeda and Oluyole local government areas of Oyo State in Nigeria in 56 randomly selected primary- (n = 42) and secondary-level (n = 2) health-care and private health-care (n = 12) facilities., Participants: One thousand consecutive, known hypertensives attending the selected facilities for follow-up, and health-care providers working in the above randomly selected facilities, were interviewed., Results: About two-thirds of hypertensives utilized primary-care centers both for diagnosis and for follow-up. Laboratory and other investigations to exclude secondary hypertension or to assess target organ damage were not available in the majority of facilities, particularly in primary care. A considerable knowledge and awareness gap related to hypertension and its complications was found, both among patients and health-care providers. Blood pressure control rates were poor (28% with systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg] and drug prescription patterns were not evidence based and cost effective. The majority of patients (73%) in this low socio-economic group (mean monthly income 73 US dollars) had to pay fully, out of their own pocket, for consultations and medications., Conclusions: If the absolute risk approach for assessment of risk and effective management of hypertension is to be implemented in low-resource settings, appropriate policy measures need to be taken to improve the competency of health-care providers, to provide basic laboratory facilities and to develop affordable financing mechanisms.

Cardiovascular diseases (CVD) account for one third of the global mortality and one tenth of the global disease burden; however, if rates of hypertension, a cardiovascular risk factor, were controlled, the reduction of the CVD burden would follow. One of the major constraints for controlling hypertension is the limitation of resources for health care, particularly in low- and middle-income countries, which contribute to 80% of the global CVD burden. Hence, it is vital to use the scarce resources with maximum efficiency. In this context, it is important to note that the benefits and cost-effectiveness of managing hypertension are determined by the overall risk of CVD and not by blood pressure level alone. Using this concept demands a paradigm shift from a "single risk" factor to an "absolute risk" approach. Unfortunately, the weak infrastructure of low-resource settings does not allow cardiovascular risk assessment using such variables as blood lipid measurements for risk stratification. Feasible risk assessment methods are needed and should use simple variables such as age, sex, smoking habits, history of premature cardiovascular disease in the family, and rates of diabetes and hypertension. To meet this need, a pragmatic CVD-Risk Management package has been developed by the World Health Organization (WHO) to facilitate cardiovascular risk assessment and management in low-resource settings. Cost-effective healthcare interventions to reduce the cardiovascular burden can only be implemented if the health services policy environment and financing enable implementation. The success of this approach will also depend on the capacity of primary heathcare systems to deliver these interventions and serve the long-term needs of high-risk CVD patients. For many countries, the individual management of large numbers of patients with low CVD risk will not be affordable. Yet, individuals at low risk, and not those at high risk, account for a greater share of the overall disease burden. Therefore, we must shift the distribution of CVD through population-wide strategies that address all major CVD risk factors, including hypertension.

The ISH Statement on blood pressure lowering and stroke prevention was finalized after presentation and discussion at the World Health Organization and International Society of Hypertension (WHO-ISH) Meeting on Stroke and Blood Pressure, held in Melbourne Australia, 5-7 December 2002. The meeting was conducted under the auspice of the Austin Hospital Medical Research Foundation, Melbourne.

Objective: To determine the association between hyperhomocysteinaemia and coronary artery disease (CAD) in a sample of Sri Lankans., Design: A case control study., Setting: Asiri Hospital, Kirula Road, Colombo 5, Sri Lanka., Subjects: 105 patients with coronary artery disease and 112 controls., Method: Fasting serum homocysteine levels were measured in 105 patients diagnosed as having CAD and in 112 unmatched controls. All patients admitted with clinical, electrocardiographical, biochemical or echocardiographical evidence of CAD were included in the study. Controls were selected from subjects admitted for health screening., Results: 105 patients with CAD and 112 controls (unmatched for age and sex) were studied. A serum homocysteine level in excess of 18.2 mumol/l was considered high. Confounding effects of other conventional risk factors for CAD were controlled using multivariate logical regression analysis., Conclusion: Hyperhomocysteinaemia is significantly associated with CAD. Multivariate logistic regression analysis indicated that the association between hyperhomocysteinaemia and CAD was confounded by other risk factors. However, statistical analysis revealed a significant independent association between hyperhomocysteinaemia and CAD (adjusted odds ratio = 2.881).

There has recently been increased publicity on the risk of venous thrombosis after long-haul flights. This paper reviews the evidence base related to the association between air travel and venous thromboembolism. The evidence consists only of case reports, clinical case-control studies and observational studies involving the use of intermediate end-points, or expert opinion. Some studies have suggested that there is no clear association, whereas others have indicated a strong relationship. On the whole it appears that there is probably a link between air travel and venous thrombosis. However, the link is likely to be weak, mainly affecting passengers with additional risk factors for venous thromboembolism. The available evidence is not adequate to allow quantification of the risk. There are insufficient scientific data on which to base specific recommendations for prevention, other than that leg exercise should be taken during travel. Further studies are urgently needed in order to identify prospectively the incidence of the condition and those at risk.

Recent studies have suggested that a chronic infection with Chlamydia pneumoniae (C. pneumoniae) may be associated with the risk of developing coronary heart disease (CHD). A case control study was conducted to investigate the association between C. pneumoniae infection and coronary heart disease and coronary risk factors in a sample South Asian population. C. pneumoniae specific IgG antibody was measured by microimmunofluorescence. Among controls 56.6% were seropositive (> or =1/32) compared to 58.5% of acute myocardial infarction (AMI) patients (n=41, odds ratio 1.08, CI 0.37--3.12, P=0.93) and 73.3% of stable coronary heart disease (SCHD) patients (n=30, odds ratio 2.1, CI 0.63--7.19, P=0.27). The highest geometric mean titre of control subjects (n=30) was significantly lower (74.7) compared to AMI patients (101.5, P<0.05) and SCHD patients (138.6, P<0.05). Patients who were non-smokers had higher odds ratios for CHD than smokers when seropositive at IgG antibody titres of 1/32, 1/64 and 1/128, suggesting an association between smoking and C. pneumoniae infection. In patients with CHD there was a significant association between diabetes mellitus and seropositivity (P=0.008) in those over 50 years of age. Non-smoking CHD patients with high cholesterol/HDL-C ratio had a higher trend for seropositivity. Other risk factors (smoking, systolic and diastolic blood pressure, waist/hip ratio, triglycerides) showed no association when controlled for age. In the control group, smokers with high cholesterol/HDL-C ratio had a higher trend for seropositivity. These results do not provide strong support for the hypothesis that C. pneumoniae infection is a risk factor for clinical CHD in this South Asian population. Results suggest that C. pneumoniae infection may be linked to CHD through its interaction with some of the known risk factors such as blood lipids, diabetes and smoking.

The aim of the present study was to examine the effect of reducing saturated fat in the diet, or partly replacing it with unsaturated fat, on the serum lipoprotein profile of human subjects. The study had two intervention periods, 8 weeks (phase 1) and 52 weeks (phase 2). In phase 1, total fat was reduced from 31 to 25% energy (polyunsaturated fatty acids (PUFA):saturated fatty acids (SFA) ratio increased from 0.2 to 0.4) by reducing the quantity of coconut fat (CF) in the diet from 17.8 to 9.3% energy intake. In phase 2, subjects were randomised to groups A and B. In group A total fat was reduced from 25 to 20% energy (PUFA:SFA ratio increased from 0.4 to 0.7) by reducing the quantity of CF in the diet from 9.3 to 4.7% total energy intake. In group B, the saturated fat content in the diet was similar to group A. In addition a test fat (a mixture of soyabean oil and sesame oil, PUFA:monosaturated fatty acids ratio 2) contributed 3.3% total energy intake and total fat contributed 24% energy intake (PUFA:SFA ratio increased from 0.7 to 1.1). At the end of phase 1, there was a 7.7% reduction in cholesterol (95% CI -3.6, -12.2) and 10.8% reduction in LDL (95% CI -4.9, -16.5) and no significant change in HDL and triacylglycerol. At the end of phase 2, the reduction in cholesterol in both groups was only about 4% (95% CI -12, 3.2) partly due the concomitant rise in HDL. The reduction in LDL at 52 weeks was significantly higher in group B (group A mean reduction 11%, 95% CI -20.1, -2.0 and group B mean reduction 16.2% 95% CI -23.5, -8.9). In phase 2, triacylglycerol levels showed a mean reduction of 6.5% in group 2A and a mean increase of 8.2% in group 2B. The reduction of saturated fat in the diet is associated with a lipoprotein profile that would be expected to reduce cardiovascular risk. The reduction of dietary saturated fat with partial replacement of unsaturated fat brings about changes in total cholesterol, HDL- and LDL-cholesterol that are associated with a lower cardiovascular risk.

Prenatally, neuroactive steroids that modulate GABAergic activity may be synthesized de novo within the fetal brain. We have examined changes in immunoreactivity staining for the steroidogenic enzymes cholesterol P450 side-chain cleavage (P450scc), and 5alpha-reductase type-2 in the cerebellum of late gestation (130-145 days gestation) fetal sheep and newborn lambs (1-4 weeks of age). Both enzymes were predominantly localized in the Purkinje cell body and dendrites of the fetal and newborn cerebellum, with weaker immunoreactivity in a few cells of the inner granular layer. P450scc immunoreactivity was present in Purkinje neurons expressing either of the neuronal microtubule associated proteins MAP1b/5 or MAP2a/b, but was absent from GFAP and HNK-1 positive cells. Soma of Purkinje neurons were also immunopositive for 5alpha-reductase type-2 in the fetuses, but expression decreased to just detectable levels in the 1-2 and 2-4 week old lambs. Both MAP1b/5- and MAP2a/b-positive Purkinje neurons showed 5alpha-reductase type-2 expression in the fetus, whereas the residual 5alpha-reductase staining in the newborn lamb was present only in MAP2a/b-positive Purkinje neurons. Allopregnanolone in the cerebellum decreased from 21.8+/-1.9 ng/g wet weight in fetuses at 140-145 days gestation to 6.7+/-0.5 ng/g in 2-4 week old lambs (P<0. 05). Thus, synthesis of neuroactive steroids from cholesterol is possible in cerebellar neurons in late gestation and persists into neonatal life, 5alpha-reductase type-2 expression is greater in the fetus compared to the neonate, and allopregnanolone concentrations in the cerebellum decrease significantly after birth.

This study examined the relationship between homocysteine and its metabolites, and hypertension in a cohort of Sri Lankan patients with essential hypertension. Serum homocysteine, cysteine, cysteinylglycine and glutathione were measured in 86 patients with a diagnosis of essential hypertension and compared with those of an age- and sex-matched control group. Patients with hypertension had significantly higher mean serum concentrations of homocysteine, cysteine and cysteinylglycine. The odds ratio for hypertension for those with a mean serum homocysteine concentration above 18 mumol/l was 2.8. Hyperhomocysteinaemia is a risk factor for hypertension in Sri Lankans and can lead to a threefold increase in risk.

Ischaemic heart disease is an emerging public health problem in Sri Lanka. Implementation of programs for lifetime control and prevention of established coronary risk factors such as smoking, hyperlipidaemia, hypertension, diabetes and hereditary risk are costly and unaffordable in countries such as Sri Lanka with limited resources for health care. Other potential risk factors which are less expensive with regard to prevention require investigation. This paper summarises several studies done over the past decade at Peradeniya, to investigate three such potential coronary risk factors of IHD, namely homocysteine, vitamin C and dietary fat.

Objective: The objective of this study was to examine the relation between hyperhomocysteinaemia and ischemic heart disease in a cohort of Sri Lankan patients with ischemic heart disease., Method: Serum homocysteine, cysteine and cysteinylglyceine were measured in 54 patients with a definite diagnosis of ischemic heart disease and compared with those of an age and sex matched control group., Results: Patients with coronary ischaemia had significantly higher mean concentrations of homocysteine and its metabolite cysteine (P<0.01). Of the 54 patients with ischemic heart disease 14 (35%) had fasting homocysteine concentrations above the 90th percentile of the controls (odds ratio 3.2, 95% CL 1.0-11.3)., Conclusion: Hyperhomocysteinaemia is associated with a three fold increase in coronary risk.

Background: Between 1979 and 1989, 48 cases of extradural spinal cord and cauda equina compression in patients with lymphoma (24) and myeloma (24) received local radiation therapy for control of cord compression. Twenty five (52%) of the cases were treated by surgical decompression prior to irradiation. Thirty five (73%) of the cases received chemotherapy following the diagnosis of spinal cord compression. Post-treatment outcome was assessed at a minimum follow-up of 24 months to determine the significant clinical and treatment factors following irradiation., Results: Seventeen (71%) of the lymphoma and 15 (63%) of the myeloma patients achieved local control, here defined as improvement to, or maintenance of ambulation with minimal or no assistance for 3 months from the start of radiotherapy. At a median follow-up of 30 (2-98) for the lymphoma and 10 (1-87) months for the myeloma patients, the results showed that survival following local radiation therapy for cord compression was independently influenced by the underlying disease type in favour of lymphoma compared to myeloma (P < 0.01). The median duration of local control and survival figures were 23 and 48 months for the lymphomas compared to 4.5 and 10 months for the myeloma cases. Survival was also independently influenced by preservation of sphincter function at initial presentation (P < 0.02) and the achievement of local control following treatment (P < 0.01)., Discussion: We conclude that while disease type independently impacts on outcome following treatment of spinal cord compression in lymphoma and myeloma, within both of these disease types the achievement of local control of spinal cord compression is an important management priority, for without local control survival may be adversely affected.

There has been a rapid increase in coronary artery disease (CAD) in most Asian countries in association with rapid economic development; however, there is no consensus of opinion on diet and lifestyle guidelines and desirable levels of risk factors for prevention of CAD in these countries. The proportion of deaths due to cardiovascular diseases in Asians may be about 15% but there are wide variations. In view of the lower fat intake of the low-risk rural populations of India, the People's Republic of China, Indonesia, Korea, Thailand and Japan compared with that of urban subjects, the limit for total energy from fat intake in an average should be 21% (7% each from saturated, polyunsaturated and mono-unsaturated fatty acids). The n-6: n-3 fatty acids ration should be < 5.0. The carbohydrates intake should be > 65% and mainly from complex carbohydrates (> 55%). A body mass index of 21 kg/m2 may be safe but the range may be 18.5-23.0 kg/m2 and someone with a body mass index > 23 kg/m2 should be considered overweight. A waist: waist:hip ratio > 0.88 for men and > 0.85 for women should be considered to define central obesity. The desirable limit for serum total cholesterol may be 170 mg/dl, the borderline high level may be 170-199 mg/dl and the high level 200 mg/dl or above. The corresponding values for low-density lipoprotein cholesterol may be 90, 90-109 and 110 mg/dl or above. Fasting serum triglycerides may be < 150 mg/dl and high-density lipoprotein cholesterol > 35 mg/dl, which are close to the levels in low-risk rural populations. Fasting blood glucose > 140 mg/dl and postprandial blood glucose > 200 mg/dl may be considered conditions for diabetes, and 140-200 mg/dl, glucose intolerance. An intake of 400 g/day fruit, vegetables and legumes, mustard or soybean oil (25 g/day) instead of hydrogenated fat, coconut oil or butter in conjunction with moderate physical activity (1255 kJ/day), cessation of tobacco consumption and moderation of alcohol intake may be an effective package of remedies for prevention of CAD in Asians.

This study examined the relationship between breath pentane and plasma lipid peroxide levels sampled simultaneously in patients with stable angina (n = 17), unstable angina (n = 23), and controls (n = 10). Plasma lipid peroxides were measured in venous blood as the adduct formed between thiobarbituric acid and malondialdehyde (MDA) using high performance liquid chromatography. Pentane was measured in end-expiratory air using gas chromatography. MDA concentrations in stable (1.81 +/- 0.84 mumol/l) and unstable (1.5 +/- 1.23 mumol/l) angina were not different. However, both groups had significantly (p < 0.005) elevated MDA levels compared to controls (0.41 +/- 0.26 mumol/l). Breath pentane was 0.20 +/- 0.12 nmol/l in controls and not different from stable angina (0.26 +/- 0.20 nmol/l) or unstable angina (0.15 +/- 0.07 nmol/l). When the data from all three groups were combined, there was no correlation between pentane and MDA (rho = -0.09, p = 0.54). In five of the unstable angina patients treated with balloon angioplasty, MDA in pulmonary arterial blood rose by 69 +/- 15% (p < 0.01), and breath pentane rose by 73 +/- 20% (p < 0.01) immediately after balloon deflation. One minute after balloon deflation MDA and pentane had returned to preinflation levels. The results suggest that basal levels of pentane are less useful than MDA as an index of lipid peroxidation in patients with coronary artery disease. However, breath pentane appears to be a sensitive index of reperfusion-induced lipid peroxidation.

Objective: To evaluate differences in Lipoprotein (a) [Lp(a)] concentrations between a Swedish and Sri Lankan population., Methods: The distribution of Lp(a) and its relation to other lipid parameters, measured with an automated turbidimetric method, in 4646 Swedes (1944 females and 2702 males) undergoing health screening and 757 randomly selected Sri Lankan males (667 non-CHD and 80 CHD subjects) was evaluated., Results: The distribution was highly skewed towards low values in both the Swedish population and the Sri Lankan male population. The Swedish population had a median of 0.16 g/L (reported as total mass) whereas the Sri Lankan population median of 0.06 g/L was much lower. For the Swedes, there was a small significant difference of 0.03 g/L between the sexes (F < M; p < 0.001) and Lp(a) was significantly higher in subjects > 50 years of age in both sexes (p < 0.002(F); p < 0.02(M)). 29% had Lp(a) values > 0.30 g/L. In the Sri Lankan males population Lp(a) was also significantly higher in subjects > 50 years of age (p < 0.009) but only 7% had an Lp(a) concentration of > 0.30 g/L. In the CHD subgroup, though not significant, subjects > 50 years of age had a lower Lp(a) concentration, indicating that Lp(a) may be a more significant risk factor in younger subjects. Both the Swedish female and male hypercholesterolemic subgroups had significantly higher Lp(a) concentrations than normolipemic subgroups and the male hypertriglyceridemic subgroups significantly lower Lp(a) concentrations than normolipemic. Great differences in Lp(a) levels are thus found between the two populations. The differences are similar in normolipemic subjects and probably they reflect mainly genetic differences. Lipid/lipoprotein concentrations were also found to differ. It is being investigated if this reflects differences in CHD prevalence., Conclusion: Our data support the importance of including Lp(a) measurements when assessing the risk profile for premature development of CHD in the individual patient.

Pentane and isoprene concentrations were analyzed in single end-expiratory breath samples using gas chromatography. Breath analysis was performed in 15 patients with acute myocardial infarction, 15 patients with stable angina, and 15 healthy control subjects. The two patient groups were well matched for age, sex, smoking habits, hypertension and serum cholesterol levels. There was no significant difference in breath pentane concentration in the acute myocardial infarction group (0.29 +/- 0.03 nmol/l) (mean +/- SEM) compared to the group with stable angina (0.31 +/- 0.03 nmol/l) or the control group (0.36 +/- 0.04 nmol/l). However, breath isoprene concentration was higher (p < 0.01) in the acute myocardial infarction group (11.4 +/- 1.2 nmol/l), compared to both the stable angina group (7.7 +/- 0.5 nmol/l) and the control group (7.1 +/- 1.0 nmol/l). There was no difference in either the pentane or isoprene concentrations between the control group and the group with stable angina. Since pentane is thought to be an index of lipid peroxidation, the results do not support the presence of enhanced lipid peroxidation in acute myocardial infarction in the absence of thrombolytic therapy or primary angioplasty. The mechanism responsible for isoprene elevation in acute myocardial infarction is unknown.

In a cross-sectional survey, we estimated the prevalence of coronary heart disease in a sample of 975 middle-aged males (35-59 years), from a defined population in the Central province of Sri Lanka using the London School of Hygiene cardiovascular questionnaire and a 12-lead electrocardiogram. The estimated prevalence rates were: (a) Definitive evidence of ischemic heart disease (positive symptoms and ECG changes of ischemia), 16/1000 (95% C.L., 9-27). (b) Evidence of coronary heart disease based on history alone 54/1000 (95% C.L., 40-71). (c) Estimate based on ECG changes of ischemia without symptoms 32/1000 (95% C.L., 21-46). Median values for major risk factors were: systolic blood pressure 120 mmHg, diastolic blood pressure 88 mmHg, serum cholesterol 4.99 mmol/l, high density lipoproteins 0.99 mmol/l and body-mass index 20.4 kg/m2. About half (57.9%) the subjects were current smokers, 17% had actual hypertension (systolic blood pressure > 159 mmHg and/or diastolic blood pressure > 94 mmHg and/or been treated for hypertension), 12.6% had hypercholesterolemia (serum cholesterol levels > 6.5 mmol/l), 18.4% had a body-mass index > 24 kg/m2 and 5.8% were diabetic. Hypercholesterolemia (> 6.5 mmol/l), a higher body-mass index (> 24 kg/m2) and diabetes were more prevalent among subjects living in an urban rather than a rural environment.

Both pentane and isoprene are excreted in human breath. Although pentane is considered an index of lipid peroxidation, the significance of isoprene is unknown. Having a similar boiling point, these two hydrocarbons are difficult to separate by gas chromatography. We separated pentane from isoprene on both a Poraplot Q and a Poraplot U column, injecting single-breath samples directly into a gas chromatograph. The breath samples were pressurized to 800 mmHg to increase the amount of sample volume delivered to the column. In a group of 43 healthy volunteers, the concentrations of end-expiratory pentane and isoprene were 0.57 +/- 0.3 and 7.05 +/- 3.53 nmol/L, respectively. There was a significant linear correlation (r = 0.57, P < 0.0001) between age and pentane concentration in expired air; isoprene showed no correlation with age or pentane concentrations. The age-related increase in pentane production suggests that oxidative stress may play a role in the aging process in humans. The method described should allow for rapid, inexpensive, serial measurement of expired pentane and isoprene.

Objective: To investigate whether drug treatment improves the electroneurological measures of affected peripheral nerve function in leprosy patients., Design: Clinical status of patients determined on the first visit by an investigator administered, pre-designed questionnaire, followed by measurement of motor conduction velocity (MCV) and distal latency (DL) of ulnar, median, common peroneal and posterior tibial nerves bilaterally in patients referred consecutively from the dermatology unit and leprosy clinic, Teaching Hospital, Galle. MCV and DL measurements were repeated after 6 to 12 months of treatment., Setting: Department of Physiology, Faculty of Medicine, University of Ruhuna, Galle., Subjects: 24 diagnosed leprosy patients; tuberculoid, lepromatous and borderline in clinical type., Interventions: Based on clinical typing. Tuberculoid (paucibacillary) type rifampicin 600 mg monthly and dapsone 100 mg daily for six months. Lepromatous and borderline (multibacillary) type rifampicin 600 mg and clofazimine 300 mg monthly and dapsone 100 mg and clofazimine 50 mg daily for 24 months., Results: DL in all 4 nerves and MCV in 3 nerves tested were significantly different (p > 0.001) to those for the normal population and remained so after 6 to 12 months of treatment. The DL in the ulnar nerve showed significant improvement (p < 0.05) after treatment. When analysed in each patient individually, before and after treatment, the MCV showed an improvement in 48 to 72% of patients and the DL in 41 to 59%, but differences were not significant., Conclusions: Electroneurological recovery (return to normal state) of the affected peripheral nerves of leprosy patients does not occur after 6 to 12 months of drug treatment. The significant (p < 0.05) improvement (becoming better) of ulnar nerve DL indicates that, if at all, electroneurologically detectable improvement of nerve function occurs in the early stages of nerve damage, and that it may take longer than one year after starting treatment.

A 30 year old woman bitten by a large Sri Lankan krait (Bungarus ceylonicus) developed progressive paralytic symptoms within one hour of the bite. After seeking traditional treatment her condition deteriorated and when she arrived at hospital 6 h after the bite she was drowsy, with bilateral ptosis and signs of aspiration pneumonia (a complication of traditional treatment). She developed an anaphylactic reaction after antivenom treatment and, despite treatment, had a cardio-respiratory arrest. She was resuscitated and mechanically ventilated, but remained deeply unconscious until her death 90 h after the bite. B. ceylonicus is endemic in Sri Lanka, is common in some areas, and could be mistaken for the common krait (B. caeruleus). It is doubtful whether any existing antivenom is effective against its venom.

We have examined DNA polymorphisms associated with the apolipoprotein B gene in 95 Sri Lankan males with ischaemic heart disease and 95 matched controls. For polymorphisms detected using the XbaI or MspI enzymes the allele frequency in Sri Lankans contrasted markedly from that in Caucasians. Overall, there was no significant association of any allele studied with coronary disease cases in this sample. There was, however, a significant difference observed between the XbaI allele frequency in normotriglyceridaemic or normocholesterolaemic CHD cases compared with the allele frequency in the controls.

A study of coronary heart disease and risk factors was conducted in a total Sri Lankan aboriginal population who face imminent extinction due to developmental programmes in the vicinity of their jungle homelands. Coronary heart disease was not detected among the aborigines. Hypertension was present in 5.7% of males and 1.9% of females. 39% of males smoked. Serum cholesterol, triglyceride and high density lipoprotein cholesterol levels were 5.25 mmol/l (SD 0.45), 1.99 mmol/l (SD 0.92) and 1.2 mmol/l (SD 0.2) respectively. Obesity was not seen and the level of physical activity was high. The rarity of coronary heart disease could be attributed to this favourable coronary risk profile.

The influence of variation in the genes for cholesteryl ester transfer protein and apolipoprotein A-I was investigated in 95 patients with coronary heart disease and 95 matched control subjects of South East Asian extraction. Restriction fragment length polymorphisms (RFLPs) linked to the cholesteryl ester transfer protein gene TaqIA and TaqIB, and to the apolipoprotein A-I gene SstI, were examined to investigate the extent of genetic variation at these loci. None of the alleles defined by these RFLPs were associated with increased coronary risk. Analysis of the data by division of high density lipoprotein-cholesterol levels into tertiles showed a trend of a higher frequency of B1 allele (presence of the TaqIB site) with reduced high density lipoprotein levels. The B1 allele was more frequent in control subjects, with low high density lipoprotein levels (P less than 0.02), but not in coronary heart disease patients. The differences became significant for both groups (P less than 0.05) when the data of non-smokers were analysed separately.

The present paper reports the influence on plasma lipids of isoenergetic diets containing 30% of energy as fat, with a polyunsaturated: saturated fat ratio of 4.00 or 0.25, consumed for 8 weeks by twenty-five young normolipidaemic males. Approximately 70% of the fat energy was provided by the test fats: soya-bean fat and coconut fat. During the soya-bean-fat-eating period the total plasma cholesterol level fell significantly compared with baseline values (P less than 0.001) and during the coconut-fat-eating phase total plasma cholesterol level increased significantly compared with the soya-bean-eating period (P less than 0.001). On the soya-bean-fat diet, high-density-lipoprotein (HDL)-cholesterol decreased by 15% (range 6-35%) and plasma triacylglycerols decreased by 25% (range 13-37%). Results of the present study show that even when the proportion of total fat in the diet is low, a high intake of linoleic acid lowers both total plasma cholesterol and HDL-cholesterol, while a high intake of saturated fat elevates both these lipid fractions. Application of regression formulas to the present findings indicates that short-chain saturated fatty acids have a neutral effect on serum cholesterol.

This study designed to examine the smoking behaviour and attitude of children were carried out on 3447, 11 to 18 year old Sri Lankan School children. The prevalence of smoking in urban and rural children are 7.2% and 4.3% respectively. 0.5% of children chew tobacco or use tobacco snuff. Friends smoking behaviour and attitude are the best predictors of smoking in children. The knowledge of health hazards of smoking is poor and is related to smoking behaviour.

The clinical features of colchicine toxicity in a patient following ingestion of Gloriosa superba tubers are described. Gastroenteritis, acute renal failure, cardiotoxicity and haematological abnormalities were the main toxic manifestations. There was no hypotension and no neurological manifestations. Electrocardiographic changes were noteworthy and have not been reported previously.

Atomic absorption spectrometry was used in a quantitative study of zinc, magnesium, and manganese on 71 postmortal human aortas. Samples were obtained from accident victims 35-65 years of age. Fibrous plaques had higher levels of all three elements when compared to normal aortic tissue. The difference was significant for zinc (p less than 0.001) and magnesium (p less than 0.01). The high elemental levels may be both a cause and effect of atherosclerosis or the result of another unknown parameter.