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Biomedical subjects

S Mendis

Publications and source records attributed to S Mendis.

At least 19 recordsLinked to original sources

Drivers of germ cell maturation.

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.

Activins↗

Prevalence of hypertension, diabetes and obesity: baseline findings of a population based survey in four provinces in Sri Lanka.

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.

Adult↗

Chlamydia pneumoniae infection and its association with coronary heart disease and cardiovascular risk factors in a sample South Asian population.

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.

Adult↗

Coconut fat and serum lipoproteins: effects of partial replacement with unsaturated fats.

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.

Adult↗

Localization of p450scc and 5alpha-reductase type-2 in the cerebellum of fetal and newborn sheep.

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.

Animals↗

Heart attacks: exploring new preventive strategies.

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.

Adult↗

Association between hyperhomocysteinemia and ischemic heart disease in Sri Lankans.

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.

Adult↗

Local control and survival in spinal cord compression from lymphoma and myeloma.

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.

Adolescent↗

Recommendations for the prevention of coronary artery disease in Asians: a scientific statement of the International College of Nutrition.

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.

Asia↗

Lipoprotein(a): levels in a Swedish population in relation to other lipid parameters and in comparison with a male Sri Lankan population.

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.

Female↗

Breath pentane and plasma lipid peroxides in ischemic heart disease.

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.

Adult↗

Expired hydrocarbons in patients with acute myocardial infarction.

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.

Adult↗

Prevalence of coronary heart disease and cardiovascular risk factors in middle aged males in a defined population in central Sri Lanka.

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.

Adult↗