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Biomedical subjects

B Tomlinson

Publications and source records attributed to B Tomlinson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Plasma ascorbic acid: measurement, stability and clinical utility revisited.

AIMS: To compare plasma ascorbic acid results by the colorimetric FRASC (Ferric Reducing/Antioxidant and Ascorbic Acid) assay and a reference HPLC method; to re-examine plasma ascorbic acid stability, and anticoagulant effect. DESIGN AND METHODS: For method comparison, 31 plasma samples were tested by both methods. For stability, matching EDTA, heparin, citrate and fluoride/oxalate plasma, stored under different conditions of time and temperature, was measured. RESULTS: FRASC is an acceptable alternative to HPLC for plasma ascorbic acid: precision, limit of detection and recovery were similar, and results by the two methods were indistinguishable: mean (95% CI) difference:1.8 (-1.1-4.6; n = 31) micromol/L. Ascorbic acid was most stable in heparinized plasma. Marked loss (p < 0.05) in EDTA plasma occurred within 30 min of blood collection. CONCLUSIONS: FRASC offers a speedy and reliable alternative to HPLC for plasma ascorbic acid. Heparin is proposed as the anticoagulant of choice; loss of ascorbic acid is rapid in EDTA plasma ex vivo.

Adult↗
PubMed2001

Head-up tilt test without intravascular cannulation in children and adolescents.

Previous studies of head-up tilt test have shown that testing at high degrees lacks specificity in children. We suspected that the high false positive rate might be related to the intravascular catheter and other maneuvers incorporated in the test and therefore studied the sensitivity and specificity of standing and HUT at 80 degrees without any invasive procedure and other maneuvers in children and adolescents. Twenty three patients (11.8+/-2.7 years) with recurrent typical neurally mediated syncope and 35 normal control children (11.6+/-3.0 years) underwent motionless standing for 15 min and tilting to 80 degrees for 30 min. Continuous finger arterial pressure monitoring and ECG were performed during the test. Eight (35%) of the 23 patients developed symptoms of near syncope during motionless standing. Thirteen (57%) of them had positive results at 80 degrees tilting for 30 min. The symptoms of syncope were not always corresponding to excessive haemodynamic changes. None of the controls developed any symptoms or excessive hemodynamic changes. Without intravascular instrumentation and other autonomic maneuvers, active motionless standing or HUT at 80 degrees for 30 min is highly specific but of limited sensitivity for the investigation of vasovagal syncope.

Adolescent↗
PubMed2001

Factor analysis of the metabolic syndrome: obesity vs insulin resistance as the central abnormality.

OBJECTIVES: To evaluate whether there is one central abnormality contributing to the conditions associated with the metabolic syndrome (MES), or whether one abnormality is contributing on multiple levels. METHODS: We recruited 145 Chinese subjects aged 17-68 y with varying degrees of insulin-sensitivity (IS): 33 healthy, 59 with type 2 diabetes mellitus, 32 essential hypertensives and 21 dyslipidaemics. IS was evaluated by the short insulin sensitivity test using a 0.1 U/kg intravenous bolus dose of insulin. Blood pressure, anthropometric measures and biochemical parameters associated with IS were also measured. Exploratory factor analyses (EFA) were performed in the entire group of 145 subjects and in the 76 with normal glucose tolerance. RESULTS: EFA in all 145 subjects defined three distinct, independent factors. Factor 1 was interpreted as general and central adiposity, impaired IS and glucose intolerance, Factor 2 was associated with hypertension and general and central obesity, whilst Factor 3 was strongly related to low HDL-cholesterol and high triglyceride concentrations and weakly to waist circumference. In patients with impaired glucose tolerance, only two factors were identified; factor 1 related to reduced IS, impaired glucose tolerance, dyslipidaemia and general and central adiposity, and factor 2 which was related to blood pressure and general and central adiposity. CONCLUSIONS: These models suggest that the clustering of variables in MES is a result of multiple factors linked by adiposity and not a single aetiology. Furthermore, increases in blood pressure are related to obesity in these Chinese subjects rather than decreased IS per se.

Abdomen↗
PubMed2001

Relationships between the taqI polymorphism of the dopamine D2 receptor and blood pressure in hyperglycaemic and normoglycaemic Chinese subjects.

BACKGROUND: We have previously reported an association of the A2 allele of the dopamine D2 receptor (DRD2) TaqI polymorphism with increased blood pressure in normoglycaemic Chinese subjects, but conversely possibly with decreased indices of obesity. Hypertension is also a common feature of patients with type 2 diabetes, with up to 50% being hypertensive. OBJECTIVE: To compare the relationship between the DRD2 TaqI polymorphism, blood pressure and obesity in Chinese patients with and without fasting hyperglycaemia. METHOD: The DRD2 TaqI polymorphism was determined by PCR-RFLP in 519 normoglycaemic and 471 hyperglycaemic Chinese subjects, of whom 53.2 and 48.8% were hypertensive, respectively. RESULTS: In the normoglycaemic subjects there was a significant increase in mean arterial pressure (P= 0.041) with increasing proportions of the A2 allele, 95 +/- 16, 96 +/- 17 and 100 +/- 17 mmHg for the A1A1, A1A2 and A2A2 genotypes, respectively. However, the relationship was not observed in the subjects with fasting hyperglycaemia either in the total group or in the subgroup who were not receiving blood pressure-lowering medication (n = 383, 97 +/- 15, 98 +/- 14 and 97 +/- 15 mmHg, respectively). When the whole group was divided into those subjects obese by either body mass index or waist-to-hip ratio (n = 484) and those subjects not obese by both these criteria (n= 506), the A1 allele (49.2 vs. 43.8%, P = 0.02) and A1 allele containing genotypes (P = 0.03) were more frequent in the obese subjects. Similar relationships were seen in the normoglycaemic and hyperglycaemic groups separately, although these did not reach significance. CONCLUSIONS: In the normoglycaemic subjects, the A2 allele was associated with increased blood pressure and possibly lower indices of obesity, but in the hyperglycaemic subjects only the possible association with obesity was noted.

Adult↗
PubMed2001

Urinary epinephrine and norepinephrine interrelations with obesity, insulin, and the metabolic syndrome in Hong Kong Chinese.

The metabolic syndrome is characterized by a clustering of cardiovascular risk factors including type 2 diabetes mellitus, hypertension, dyslipidemia, and obesity. Elevated plasma insulin and urinary norepinephrine (noradrenaline) and reduced urinary epinephrine (adrenaline) excretion are associated with obesity in Caucasian populations. We examined the interrelationships between obesity, plasma insulin, and urinary catecholamine excretion in Chinese subjects with various components of the metabolic syndrome. A total of 577 Chinese subjects (aged 38 +/- 10 years; 68% with type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria and 32% healthy subjects) were studied, all of whom had a plasma creatinine less than 150 micromol/L. The blood pressure, height, weight, waist and hip circumference, and fasting plasma glucose, insulin, lipid, and creatinine levels were measured. A 24-hour urine sample was collected for measurement of albumin and catecholamine excretion. The body mass index (BMI) and waist circumference were used as measures of general and central obesity, respectively. The insulin resistance index was estimated by the calculated product of fasting plasma insulin and glucose concentrations. Patients with an increasing number of components of the metabolic syndrome (type 2 diabetes mellitus, hypertension, dyslipidemia, obesity, and/or albuminuria) were more obese, hyperglycemic, dyslipidemic, and albuminuric and had higher blood pressure, plasma insulin, insulin resistance indices, and 24-hour urinary norepinephrine excretion but lower urinary epinephrine output (all P < .005). Increasing quintiles of BMI in the whole population or waist circumference in both sexes were associated with increasing trends for adverse lipid profiles, plasma insulin, insulin resistance indices, and urinary norepinephrine excretion but a decreasing trend for urinary epinephrine output (all P < .001). There were close associations between age, obesity, blood pressure, fasting plasma glucose, lipid, insulin, insulin resistance indices, and urinary catecholamine excretion. Using stepwise multiple regression analysis (all P < .001), 34% of the variability of the BMI and 45% of that of the waist circumference were independently related to gender (waist higher in males and BMI higher in females), increased plasma insulin, triglyceride, and urinary norepinephrine excretion, and decreased high-density lipoprotein (HDL) cholesterol and urinary epinephrine output. In Chinese subjects with different manifestations of the metabolic syndrome, hyperinsulinemia, insulin resistance, elevated norepinephrine, and reduced epinephrine excretion were closely associated with general and central obesity. Based on these findings, we postulate that complex interactions between the insulin and sympathoadrenal systems may lead to the development of obesity and the metabolic syndrome.

Adult↗
PubMed2001

How well tolerated are lipid-lowering drugs?

It has been clearly established that lipid-lowering treatments [such as 3-hydroxyl-3-methylglutamyl coenzyme A reductase inhibitors ('statins') or fibrates] can reduce cardiovascular events, and with one of the statins even total mortality, in high-risk populations. Intervention studies have not included the very old, but it is generally assumed that this patient group would benefit from these treatments to an extent similar to younger patients. Worries about the associations seen in observational studies between low cholesterol levels and cancer, cerebral haemorrhage or mood and behaviour change have been largely overcome by findings from the latest large drug intervention trials, which do not show any increase in these conditions with statin or fibrate treatments. The common adverse effects associated with these drugs are relatively mild and often transient in nature. Potentially more serious adverse effects, which are more clearly related to drug treatment and are probably dose-dependent, include elevations in hepatic transaminase levels and myopathy; however, these effects are uncommon and generally resolve rapidly when treatment is stopped. The risk of myopathy with fibrate treatment is increased in patients with renal impairment, and the risk of myopathy with statin treatment increases with co-administration of drugs that inhibit statin metabolism or transport. Other adverse effects are related to specific drugs, for example, clofibrate is associated with an increased risk of gallstones. Studies in elderly patients have not shown an increased risk of adverse effects with lipid-lowering drugs compared with younger patients, but in clinical practice there may be some increased risk, particularly with regards to drug interactions. Therefore, lipid-lowering drugs should be administered with extra caution to elderly patients.

Age Factors↗
PubMed2001

Renin-angiotensin system gene polymorphisms, blood pressure, dyslipidemia, and diabetes in Hong Kong Chinese: a significant association of tne ACE insertion/deletion polymorphism with type 2 diabetes.

OBJECTIVE: In Chinese populations, hypertension is common and is a major risk factor for cerebrovascular and coronary heart disease, particularly when associated with diabetes. The clustering of these disorders and dyslipidemia and obesity is termed the metabolic syndrome and is increasing in prevalence in the populations of modernizing Asian nations. The renin-angiotensin system (RAS) helps maintain blood pressure and salt homeostasis and may play a role in the pathogenesis of aspects of the metabolic syndrome. We investigated three RAS gene polymorphisms--the ACE insertion/deletion (I/D), angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms--for a possible role in modulating these disorders in 853 Chinese subjects with varying components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: The three gene polymorphisms of this cross-sectional study were detected using polymerase chain reaction-based protocols. The genotype frequencies were compared between the controls (n = 119) and both overlapping and nonoverlapping groups of patients with type 2 diabetes, hypertension, and dyslipidemia using chi2 test. Differences in levels of the biochemical parameters between the genotypes were determined using analysis of variance. RESULTS: No significant relationship was identified between these polymorphisms and blood pressure in this population. Although the AT1RA1166C polymorphism was not associated with any aspect of the metabolic syndrome examined, there was limited evidence to suggest that the AGT M235T polymorphism may be associated with cholesterol levels. The ACE I allele was significantly more frequent in each group comprising subjects with type 2 diabetes/glucose intolerance (GIT), and the I allele was associated with higher fasting plasma glucose levels. CONCLUSIONS: These findings suggest that these polymorphisms are unlikely to be involved in the pathogenesis of hypertension. The ACE I/D polymorphism was associated with the metabolic syndrome, having a higher frequency of I allele-containing genotypes in those groups, but this appeared to result predominantly from the relationship with type 2 diabetes/GIT in this population of Chinese subjects.

Adult↗
PubMed2001

Albuminuria and the renin-angiotensin system gene polymorphisms in type-2-diabetic and in normoglycemic hypertensive Chinese.

BACKGROUND: Albuminuria predicts nephropathy-related mortality in Caucasian and Chinese populations. The involvement of renin-angiotensin system (RAS) gene polymorphisms in the pathogenesis of nephropathy has been described predominantly in Caucasian populations. We have previously suggested that the angiotensinogen 235T variant may be associated with nephropathy in diabetic Chinese. PATIENTS AND METHODS: To validate these findings and extend them to include non-diabetic nephropathy, we examined the association of albuminuria and gene polymorphisms of the angiotensinogen M235T, angiotensin-converting enzyme insertion/deletion and angiotensin II type I receptor A1166C polymorphisms in 614 Chinese subjects (66% type 2 diabetic, 16% normoglycemic hypertensives and 18% controls). RESULTS: Obesity and higher blood pressure were associated with albuminuria in both diabetes and normoglycemic hypertension. In the diabetic group, albuminuria was also associated with increased insulin resistance and glycemic indices, duration of diabetes and adverse lipid profiles. Only the ACE gene polymorphism showed evidence of association with albuminuria, with the D allele being less frequent in the normoglycemic hypertensive patients with albuminuria (25.0%) than the controls (41.4%) or normoalbuminuric group (39.6%) and in those hypertensives at increased risk (albumin-to-creatinine ratio > 5.6 mg/mmol) of end-stage renal disease than those at lower risk (all p < 0.05), but not in the diabetic group. The D allele was also less prevalent in the total (31.9%) and normoalbuminuric (32.2%) diabetic groups than in the controls (p < 0.05). CONCLUSION: In this cohort of Chinese subjects, the ACE gene polymorphism D allele was less frequent in normoglycemic hypertensive patients with albuminuria and in type 2 diabetes.

Adult↗
PubMed2001

[Protection against paracetamol-induced hepatic damage using total flavonoids of Astragalus].

OBJECTIVE: To study the mechanism of the protection by total flavonoids of Astragalus protection against paracetamol-induced hepatic damage. METHOD: Analysing paracetamol and its metabolites in mice urine by HPLC and studying the mechanism of anti-damage induced by paracetamol using experiment module of pentobarbital-induced sleeping time. RESULT: Administration of large doses of paracetamol to C57BL/6J mice produced significant hepatic injury with marked elevation in serum ALT activity and severe hepatocellular necrosis. TFA showed a good protective capability against paracetamol-induced hepatic injury. TFA had no marked effect on paracetamol and its metabolites except for the mercapturate-conjugate. The concentration of mercapturate change decreased with increasing TFA dose. TFA had no effect on the pentobarbital metabolites (P > 0.05). However, paracetamol (400 mg.kg-1) prolonged the sleeping time (by 110 min relative to the controls, P < 0.001). The TFA (P < 0.005) caused significant reduction in paracetamol-prolonged pentobarbital-induced sleep. CONCLUSIONS: The mechanism of TFA's protective effect against the paracetamol-induced damage may be related to the inhibition of some metabolism progress of paracetamol and the reduction of the toxicity metabolite such as mercapturate-conjugate.

Acetaminophen↗
PubMed2000

An insulin receptor gene polymorphism is associated with diastolic blood pressure in Chinese subjects with components of the metabolic syndrome.

Insulin resistance has been described as a possible underlying link for the clustering of Type 2 diabetes mellitus, hypertension, obesity, and dyslipidemia, known as the metabolic syndrome. Mutations within the insulin receptor have been associated with hypertension in some white and Oriental populations. We examined the relationship between the insulin receptor NsiI restriction fragment-length polymorphism (RFLP) and biochemical and anthropometric parameters associated with these disorders in 933 Chinese subjects. Of the 933 subjects, 117 were control subjects and 816 had one or more components of the metabolic syndrome: 59.7% hypertension, 64.6% glucose intolerance, 55.3% dyslipidemia, and 53.3% obesity. The prevalences of the N1 allele and N1N1 genotype were 74.4% and 55.8%, respectively, in the whole population. No differences were observed in the genotype and allele frequency distributions between the control group and the cohorts with glucose intolerance, hypertension, or dyslipidemia alone or in combination. Using one-way ANOVA, there was a weak relationship between the insulin receptor genotypes and diastolic blood pressure (DBP), P = .069. The DBP was significantly higher in subjects carrying the N1N1 genotype in both the total population (80 +/- 13 v 76 +/- 12 mm Hg, P = .038) and subjects with glucose intolerance (80 +/- 12 v 76 +/- 10 mm Hg, P = .048). Using stepwise multiple regression, the insulin receptor NsiI polymorphism was found to be an independent predictor of DBP in this Chinese population, P = .018. Age, gender, and body mass index (BMI) were also included in the analysis and were all significantly associated with diastolic DBP. To conclude, the insulin receptor gene NsiI RFLP is associated with DBP in these Chinese subjects.

Adult↗
PubMed2000

The Trp64Arg polymorphism of the beta3-adrenergic receptor gene and obesity in Chinese subjects with components of the metabolic syndrome.

BACKGROUND: In regions such as Hong Kong, rapid economic development has led to lifestyle alterations characterized by increases in energy and fat intake and reduction in physical activity. These changes have been associated with a dramatic increase in the prevalence of diabetes and related diseases of the metabolic syndrome. OBJECTIVE: To investigate if a common polymorphism (Trp64Arg) of the beta3-adrenergic receptor gene, previously implicated as predisposing to type 2 diabetes mellitus or obesity in other populations, has a role in the apparent susceptibility of Hong Kong Chinese to diabetes and related disorders. METHOD: A PCR-based protocol was used to genotype 802 Southern Chinese subjects who were either healthy or had one or more of the metabolic disorders including diabetes, hypertension or dyslipidaemia. RESULTS: The frequencies of the mutant A allele (12.7%) and AA genotype (1.7%) did not differ, by the chi2 test, in any patient group with diabetes, hypertension or dyslipidaemia, alone or in combination, compared to healthy controls. Using the t-test in the 802 subjects, those carrying the mutant A allele had evidence of increased obesity with a significantly (all P<0.05) higher body mass index (BMI, kg/m2) and also lower HDL-cholesterol. BMI was also elevated in subjects with the A allele in the separate groups with diabetes, dyslipidaemia or hypertension. Stepwise multiple regression showed this polymorphism to be an independent predictor of BMI. CONCLUSION: These data do not support any direct involvement of the Trp64Arg polymorphism in the development of diabetes, hypertension or dyslipidaemia in Chinese subjects, but do suggest a relationship with obesity.

Adult↗
PubMed2000

A double-blind placebo-controlled study of the effectiveness and tolerability of oral stevioside in human hypertension.

AIMS: Stevioside is a natural plant glycoside isolated from the plant Stevia rebaudiana which has been commercialized as a sweetener in Japan for more than 20 years. Previous animal studies have shown that stevioside has an antihypertensive effect. This study was to designed to evaluate the effect of stevioside in human hypertension. METHODS: A multicentre, randomized, double-blind, placebo-controlled study was undertaken. This study group consisted of 106 Chinese hypertensive subjects with diastolic blood pressure between 95 and 110 mmHg and ages ranging from 28 to 75 years with 60 subjects (men 34, women 26; mean +/- s.d., 54.1+/-3.8 years) allocated to active treatment and 46 (men 19, women 27; mean +/- s.d., 53.7+/-4.1 years) to placebo treatment. Each subject was given capsules containing stevioside (250 mg) or placebo thrice daily and followed-up at monthly intervals for 1 year. RESULTS: After 3 months, the systolic and diastolic blood pressure of the stevioside group decreased significantly (systolic: 166.0+/-9.4-152.6+/-6.8 mmHg; diastolic: 104.7 +/- 5.2-90.3+/-3.6 mmHg, P<0.05), and the effect persisted during the whole year. Blood biochemistry parameters including lipid and glucose showed no significant changes. No significant adverse effect was observed and quality of life assessment showed no deterioration. CONCLUSIONS: This study shows that oral stevioside is a well tolerated and effective modality that may be considered as an alternative or supplementary therapy for patients with hypertension.

Adult↗
PubMed2000

Compound heterozygosity of Leu252Val and Leu252Arg causing lipoprotein lipase deficiency in a chinese patient with hypertriglyceridemia.

BACKGROUND: We investigated lipoprotein lipase (LPL) gene mutations in a Chinese male with severe hypertriglyceridemia and recurrent pancreatitis. METHODS: We screened for LPL sequence mutation in the LPL gene in this patient, his relatives and 160 unrelated hypertriglyceridaemic subjects. We determined the postheparin plasma LPL activity of subjects carrying a LPL mutation and studied the in vitro expression of mutant LPL in COS-1 cells. RESULTS: The proband was found to be a compound heterozygote for a novel Leu252Val and a reported Leu252Arg mutation in the LPL gene. He had low plasma levels of postheparin LPL activity and mass. The two mutations segregated independently in his family. In vitro expression analysis showed that Leu252Arg abolished both the catalytic function and secretion of LPL, while Leu252Val abolished the catalytic function but only reduced secretion by about half. We have also detected heterozygous Leu252Val and Leu252Arg mutations each in one hypertriglyceridaemic individual. CONCLUSION: These results indicated that the leucine 252 is critical for the catalytic activity and secretion of LPL. Why the substitution by valine instead of arginine resulted only in a partial suppression of LPL secretion, remains to be investigated. Leu252Val and Leu252Arg are the likely cause of hypertriglyceridemia in these subjects because of their deleterious effects on LPL activity or secretion. Leu252Val/Leu252Arg is the first compound heterozygous mutation known to occur in the same codon of the LPL gene. So far they are found only in Chinese.

Adolescent↗
PubMed2000

Renal kallikrein-kinin system, but not renal dopamine system, mediates the natriuretic response to intravenous saline infusion in healthy Chinese subjects.

1. To assess the role of renal dopamine (DA), sympathetic nervous system (SNS) activity and the renal kallikrein-kinin system in sodium excretion in Chinese subjects, we studied the effects of intravenous saline infusion on the urinary excretions of sodium, free DA, free noradrenaline (NA) and kallikrein in eight healthy males aged 23-25 years. 2. After a baseline period of 1 h (hour 0), these subjects received 11 of 0.9% saline over 2 h (hours 1 and 2), followed by a 4-h recovery period (hours 3-6). From hours 0-4, subjects remained in the supine position, except to void urine. Distilled water was given orally throughout the study to ensure an adequate diuresis. 3. A 31-39% increase in sodium excretion (P < 0.05) was seen during hours 2 and 3. Urinary DA did not change throughout the study period. Urinary free NA showed no changes while the subjects remained supine, but an increase of 91-105% (P < 0.02) was seen after the subjects became ambulatory. However, there was a 103-140% increase in urinary kallikrein excretion (P < 0.05) during the saline infusion. Urinary kallikrein was still much higher (by 74%) than the basal level 1 h after the completion of the saline infusion. 4. There is no evidence from the present study that renal DA or SNS play any role in the natriuretic response to saline infusion in Chinese subjects. The brisk urinary kallikrein response, despite a relatively small salt load, suggests that the renal kallikrein-kinin system may play an important role in extracellular fluid volume and sodium homeostasis in Chinese subjects.

Adult↗
PubMed2000

Effects of trilinolein on superoxide dismutase activity and mrna levels in aortic smooth muscle cells.

1. Atherosclerotic cardiovascular disease is still the leading cause of death in Western countries. Oxygen free radicals are considered to be intimately involved in the development of atherosclerosis. Anti-oxidants may help to protect mammalian cells from the damage induced by these reactive oxygen species. Many reports have indicated that anti-oxidants used in the treatment or prevention of disease could modify the levels of superoxide dismutase (SOD). However, the effects of long-term anti-oxidant treatment on the levels of SOD in smooth muscle cells (SMC) is still unclear. In the present study, the effects of the lipophilic anti-oxidant trilinolein on the activity and gene expression of SOD in SMC were evaluated. 2. After 2 days incubation with 0.1 micromol/L trilinolein, the activity and mRNA levels of SOD were increased in rat aortic SMC (A7r5), but there was no significant change in these parameters with a higher concentration of 1 micromol/L trilinolein. 3. In contrast, after 7 days incubation with trilinolein, both the activity and mRNA levels of SOD were lowered in a dose-dependent manner. 4. These data emphasize the importance of choosing an optimal dosage for supplementation with anti-oxidants in humans for the scavenging of oxygen free radicals.

Animals↗