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Biomedical subjects

M H Tan

Publications and source records attributed to M H Tan.

At least 73 records · Page 4Linked to original sources

Comparative efficacy and safety of pravastatin, nicotinic acid and the two combined in patients with hypercholesterolemia.

In a comparative study, 158 patients with type IIa or IIb primary hypercholesterolemia received either placebo, nicotinic acid extended-release capsules (0.5 to 1.0 g twice daily), pravastatin (40 mg at bedtime), or the combination for a short-term, 8-week period. A long-term, 88-week phase followed in which the addition of other lipid-lowering agents was permitted. During the short-term phase, low-density lipoprotein cholesterol levels were lower, in relation to baseline, with nicotinic acid treatment (-21%) than with placebo (P < or = 0.05), with pravastatin (-33%) than with either placebo (p < or = 0.001) or nicotinic acid (p < or = 0.05) and with combination therapy (-49%) than with the other 3 treatments (p < or = 0.05) at all weeks measured. At week 8, high-density lipoprotein cholesterol levels were increased, in relation to placebo, by nicotinic acid treatment (12%; p < or = 0.05), pravastatin therapy (13%; p < or = 0.01) and combination therapy (16%; p < or = 0.01). Adverse events were less frequent in the pravastatin and placebo groups (p < or = 0.05). In comparison with placebo, treatment with nicotinic acid resulted in significant increases in aspartate and alanine aminotransferase. The placebo and pravastatin groups did not differ significantly regarding adverse events or laboratory parameters. Similar results were observed in the long-term phase. Therefore, pravastatin is very effective and well tolerated in the treatment of type IIa or IIb primary hypercholesterolemia, and is superior to nicotinic acid in both efficacy and adverse event profile.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Detection of familial defective apolipoprotein B-100 among patients clinically diagnosed with heterozygous familial hypercholesterolemia in maritime Canada.

Familial defective apolipoprotein B-100 (FDB) is a genetic disorder resulting from a mutation in the apolipoprotein B-100 (apo B-100) gene, most frequently at position 3500, in which arginine is substituted for glutamine in the mature protein. This mutation drastically decreases the affinity of the mutant apo B-100 particle for the low-density lipoprotein (LDL) receptor, and hence decreases the clearance of cholesterol from the circulation. Familial hypercholesterolemia (FH), also a disorder of lipid metabolism, results from mutations in the gene for the LDL receptor. Both FDB and heterozygous FH occur at approximately the same frequency (1 in 500) among Caucasians and both produce clinical symptoms and signs that can be indistinguishable. Polymerase chain reaction (PCR) amplification and subsequent restriction analysis have been used to detect the substitution at codon 3500 in the apo B-100 gene using mutagenic PCR primers. At least one proband from 10 unrelated families with a history of hypercholesterolemia was screened by mutagenic PCR for FDB. Only one of 10 patients demonstrated the mutation for FDB. The mutant apo B-100 allele was shown to segregate with other clinically affected family members. These results demonstrate that molecular analysis is essential to distinguish between FDB and heterozygous FH in hypercholesterolemic families.

Adult↗

Determinants of diet glycemic index calculated retrospectively from diet records of 342 individuals with non-insulin-dependent diabetes mellitus.

Controlled trials have shown that a diet with a low glycemic index improves blood glucose and lipid control in patients with diabetes. To study the distribution and determinants of diet glycemic index, we obtained two 3-d diet records from 342 free-living subjects with non-insulin-dependent diabetes. Mean +/- SD 24-h intakes were as follows: energy, 7170 +/- 1890 kJ; fat, 33.6 +/- 6.5% of energy; protein, 20.1 +/- 3.2% of energy; available carbohydrate, 45.3 +/- 7.2% of energy; and dietary fiber, 17.2 +/- 6.4 g. Diet glycemic index values (85.4 +/- 4.55, range, 70-97.8) were normally distributed. Diet glycemic index was inversely associated with intake of simple sugars, whether expressed in grams (r = -0.426), percent of energy (r = -0.446), or percent of carbohydrate (r = -0.453, P < 0.001). By step-wise-multiple-linear regression, grams carbohydrate and percent protein were also independently related to diet glycemic index. Differences in diet glycemic index between men and women, and between subjects on different types of diabetes therapy were explained by differences in intake of simple sugars.

Blood Glucose↗

Expression of the insulin-regulatable transporter GLUT-4 in muscle is influenced by neurogenic factors.

To investigate whether the expression of GLUT-4 is influenced by neurogenic factor(s) released from the nerve to the muscle, we measured GLUT-4 at different time points after sectioning the sciatic nerve at different locations in two groups of rats. Specifically, GLUT-4 was measured at 12, 24, and 48 h after severing the sciatic nerve. In one group of animals the muscles were left either with a short nerve stump attached to the muscle, or, in another group of animals, a long nerve stump remained attached to the muscle. In both groups of animals the contralateral limb served as a control. We examined GLUT-4 in the red (RG) and white gastrocnemius (WG), since the RG is highly responsive to denervation and the WG is quite resistant to denervation [L. A. Megeney, P.D. Neufer, G. L. Dohm, M. H. Tan, C. A. Blewtt, G. C. B. Elder, and A. Bonen. Am. J. Physiol. 264 (Endocrinol. Metab. 27): E583-E593, 1993]. In the long nerve stump WG no change in GLUT-4 was observed at 12, 24, or 48 h after denervation (P > 0.05). In the short nerve stump WG, changes were not evident at 12 and 24 h (P > 0.05), but by 48 h a significant decrement (-12.7 +/- 6.7%) was observed (P < 0.05). GLUT-4 changes were only evident 48 h after denervation (-19.8 +/- 4.5%; P < 0.05) in the long nerve stump RG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Insulin availability among International Diabetes Federation member associations. Report of the Task Force on Insulin Distribution.

OBJECTIVE: To assess the availability of insulin and diabetes supplies among International Diabetes Federation (IDF) member associations. RESEARCH DESIGN AND METHODS: A mail survey of IDF member associations asked about the following issues: 1) diabetes prevalence and insulin use, 2) availability and cost of insulin and supplies, 3) availability of glycemic monitoring supplies, 4) cost of insulin and supplies to patients, and 5) availability of oral hypoglycemic agents. RESULTS: Of 85 member associations, 60 responded. The mean prevalence of diabetes was 3.7%. Of the 39 with a population-based survey data, the prevalence was 3.9%. Insulin use was reported for 19.2% of diabetes patients and, for the 15 with population-based data, the proportion using insulin was 16.1%. Of the respondents, 47 (78%) reported insulin was always available, 11 (18%) reported insulin was available from 25 to 99% of the time, and 2 (Uganda and Tanzania) reported insulin was available < 25% of the time. Insulin is free to patients in 39 (65%) of the countries. The average cost of the least expensive insulin was U.S. $9.62 per vial. Fifteen countries imposed a mean 13% customs charge. Disposable syringes were available in 42 (72%) of countries all of the time. Glucose meters were in use in 49 countries. The most common oral agent was glyburide, which was available in 57 countries. CONCLUSIONS: Insulin is in reasonable supply in IDF member countries. Cost and customs charges are an impediment to universal access. IDF now can recommend programs based on this data.

Diabetes Mellitus↗

Disease and risk factor perception among patients with coronary artery disease in Kuala Terengganu.

One hundred consecutive patients with coronary heart disease attending the Physician Clinic, Kuala Terengganu General Hospital self-completed a questionnaire on their awareness of the coronary risk factors and their perception of their disease. Seventy-one subjects were males. Twenty-seven subjects had never had formal education and only 6 had completed tertiary education. Whilst 52% considered themselves as having less than 25% knowledge about their disease, many were aware of hypercholesterolaemia, emotional stress, inadequate exercise and smoking as risk factors for coronary heart disease. Diabetes and family history were less known as coronary risk factors. Despite their awareness of the risk factors, though, the subjects failed to control these. For example, smoking was prevalent and their awareness of the harmful effects of smoking did not seem to deter them from this habit. Further, formal education did not seem to influence positive health behaviour. In terms of disease perception, the subjects tended to believe that their illness could be cured. Eighty subjects expected a cure from their doctors. Sixty-three subjects wanted more explanation of their illness from their doctors. These findings suggest that efforts should be made to translate patients' awareness of their illness to appropriate health behaviour, and perhaps doctors could achieve this by spending more time explaining to the patients, and educating them.

Aged↗

Descriptive terms used by Malay patients for exertional angina pectoris.

Description of the chest pain of angina pectoris by patients is commonly used in the diagnosis, evaluation and monitoring of ischaemic heart disease. Whilst certain descriptive terms have been identified as describing angina and not other causes of chest pain, these terms have not been systematically evaluated among local Malaysian patients. Reliance on a translation of the description used by Western patients may not be totally correct in the local context. Seventy-one Malay patients with documented ischaemic heart disease were asked, by questionnaire and by interview, to identify the descriptive terms they used for their angina pectoris. Common terms used by these patients were sempit (constrictive) [56.3%], mencuck (pricking) [54.9%], berat (heavy) [53.5%], panas (burning) [50.7%], menekan (pressing) [46.4%], and pedih (smarting) [43.7%]. Other less common descriptions used were tajam (sharp), mencengkam (strangulating), hempap (compressive), ngilu, hiris (knife-like), lengoh (aching). Two-thirds of the patients used more than three terms to describe their angina pectoris. Direct translation of the description of angina may not only be inaccurate but could also be misleading. It is suggested that the actual words used by the patients in Bahasa Malaysia be recorded in the patient's notes rather than a translation of these. More studies are required to determine whether the terms used by the patients in this study are related to local dialect (in this case Terengganu) or are actually common in Malaysia. Further, similar studies among Chinese and Indian patients are also required.

Angina Pectoris↗

Effects of muscle activity and fiber composition on glucose transport and GLUT-4.

We examined glucose uptake and GLUT-4 in rat muscles [soleus (Sol), plantaris (PL), extensor digitorum longus (EDL), tibialis anterior, and the red and white gastrocnemius (WG)]. In the normally innervated perfused rat hindlimb muscles the proportion of oxidative fibers was highly correlated with the muscle's insulin-stimulated 3-O-methyl-D-glucose (3-MG) uptake (R2 = 0.78) and GLUT-4 content (r = 0.94). Insulin-stimulated 3-MG uptake and GLUT-4 were also highly correlated (R2 = 0.996). In 3-day denervated muscles, insulin-stimulated 3-MG uptake was reduced in all six muscles (-41 to -14.6%, P < 0.05), and GLUT-4 content was also reduced (-87.5 to -34.9%), except in the WG and EDL (P > 0.05). A very high correlation was observed between the decrements in GLUT-4 (%) and the decrements in 3-MG uptake (%; r = 0.99). The relatively greater loss in muscle activity (%) due to denervation in the Sol compared with the PL coincided with the reductions (%) in GLUT-4 and 3-MG uptake. These studies demonstrate that glucose uptake and GLUT-4 are regulated by insulin-independent means, namely the oxidative capacity of the muscle and the normal activity level of the muscle.

3-O-Methylglucose↗

Epinephrine administration stimulates GLUT4 translocation but reduces glucose transport in muscle.

Epinephrine opposes glucose transport in muscle. Therefore, we investigated the effects of epinephrine administration (25 micrograms/100g body weight) on glucose transport and glucose transporters in rat muscle. Ninety minutes after epinephrine injection 3-O-methyl glucose transport was reduced (approximately 47%) in perfused muscles of the rat hindlimb. Translocation of the insulin-regulatable glucose transporter (GLUT4) in the epinephrine-injected animals was confirmed by the marked increments in the GLUT-4 in the plasma membranes and their concomitant reduction in the intracellular membranes. We speculate a) that it is epinephrine which translocated GLUT4 via a cAMP-linked pathway, and b) that the intrinsic activity reductions are caused either by the glycation of the transporter by the persistent hyperglycemia and/or by epinephrine via the phosphorylation of the GLUT4 transporter protein in muscle.

3-O-Methylglucose↗

Increased glucose transport in nonexercising muscle.

Changes in blood flow and muscle glycogen in nonexercising muscle during exercise suggest that glucose transport may be increased in nonexercising muscles. Therefore, we compared 3-O-methyl-D-glucose (3-MG) transport in exercised and nonexercised perfused rat hindlimb muscles (soleus, plantaris, and red and white gastrocnemius), in the absence and presence of insulin (30 nM). Specifically, the following four treatments were used: 1) normal rest, 2) normal exercise animals (90 min running 15 m/min, 8% grade), 3) hindlimb-suspended animals at rest (90 min), and 4) hindlimb-suspended animals while exercising on the forelimbs (90 min running 15 m/min, 8% grade). In separate groups of animals, it was shown from the analyses of the electromyographic interference patterns that muscle activity was sharply reduced in hindlimb-suspended muscles both at rest and during exercise (soleus and plantaris). Glycogen decrements were also observed in nonexercising muscles during exercise (soleus, plantaris, and red gastrocnemius; P less than 0.05), although these decrements were less than in the exercised muscles (P less than 0.05). Glucose transport differed among muscles (soleus = plantaris greater than red gastrocnemius greater than white gastrocnemius), and typical increments were observed after exercise (P less than 0.05) and with insulin stimulation (P less than 0.05). An additive effect of insulin and exercise was also observed (P less than 0.05). In nonexercised muscles with no insulin in the perfusate, an increase in 3-MG transport occurred (P less than 0.05). In the presence of insulin, an increase in 3-MG transport was also observed in the nonexercised red and white gastrocnemius muscles (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Persistence of glucose metabolism after exercise in trained and untrained soleus muscle.

We tested the hypothesis that increments in glucose metabolism in muscles from trained animals are caused by training adaptations in skeletal muscle and not by the residual effects of the last training session. The effects of a single bout of exercise on glucose metabolism (glycolysis and glycogenesis) were compared, against appropriate controls, in untrained (experiment 1) and trained (experiment 2) rat soleus muscles immediately (t = 0) and 3, 6, 24, 48, and 96 h after a standardized bout of exercise. [3H]Glucose incorporation into glycogen and glycolysis was measured in vitro in the absence and presence of insulin (0.1 and 10 nM). Experiment 1: A single bout of exercise provoked an increase in glycogenesis in the exercised, untrained muscles compared with the nonexercised, untrained muscles (0-96 h; P = 0.006). Glycolysis was not altered (0-96 h; P > 0.05). Experiment 2: In the exercised trained soleus, rates of glycolysis were greater than in the exercised, untrained soleus, at insulin concentrations of 0.1 nM (0-96 h; P = 0.005) and 10 nM (0-96 h; P = 0.01), but not in the absence of insulin (0-96 h; P > 0.05). No differences were observed in the rates of glycogenesis (0-96 h; P > 0.05). Therefore, acute exercise provokes increments in glycogenesis, whereas training increases glycolysis, in the presence of insulin, for some time after exercise. We speculate that insulin-dependent increments in glycolysis in trained muscles are a consequence of increased glucose transport caused by a greater pool of insulin-translocatable, intracellular glucose transporters.

Analysis of Variance↗

Antiphospholipid antibodies require beta 2-glycoprotein I (apolipoprotein H) as cofactor.

IgG was isolated from 9 patients with high levels of anticardiolipin antibodies (aCL). The standard ELISA was modified, using gelatin to postcoat ELISA plates and as diluent. Under these conditions, 8/9 samples of IgG bound to cardiolipin only in the presence of a cofactor, found in fetal calf serum and normal human serum (NHS). beta 2-glycoprotein I (apolipoprotein H) was at least as effective as NHS as a cofactor for 7/9 IgG samples. Our studies confirm that for some aCL detected in conventional assays, the antibody will react with cardiolipin only if beta 2-glycoprotein I is present.

Antibodies, Antiphospholipid↗

Follow-up of cyclosporin A treatment in type 1 (insulin-dependent) diabetes mellitus: lack of long-term effects.

In the Canadian/European randomized controlled study on cyclosporin A (CsA) in recent onset Type 1 (insulin-dependent) diabetes, treatment with the immunosuppressive drug had increased and maintained Beta-cell function and clinical remission during the first 12 months. Following discontinuation of the study drug and double-blinding after a mean of 13.8 months former CsA patients doubled the daily insulin dose within 6 months reaching the level of former placebo patients. The difference in Beta-cell function between the two groups was also lost. Metabolic control (HbA1c) was transiently worse in the former CsA group. Adverse effects of cyclosporin A on systolic blood pressure, haemoglobin levels, serum potassium and creatinine levels also remitted during that time. We conclude that treatment with cyclosporin A for a mean of 13.8 months had no long-lasting effect on the course of Type 1 diabetes persisting beyond drug discontinuation.

Adolescent↗

Diabetes mellitus in Canada.

In this overview of diabetes mellitus in Canada, we discussed the following: (1) the increasing prevalence of diabetes from 2.4% known diabetes in 1985 to 5% in 1989; (2) the incidence of diabetes in Prince Edward Island and the marked variation of incidence of insulin-dependent diabetes mellitus between Montreal (9.2/100,000) and Prince Edward Island (25.5/100,000); (3) the marked variation in prevalence of diabetes in native Indians in various parts of the nation; (4) the high prevalence of microangiopathy and macroangiopathy in people with diabetes in Southern Alberta; and (5) mortality from diabetes in Prince Edward Island.

Age Factors↗

Changes in the composition of plasma lipoproteins in the chronic uremic rat.

The effect of chronic renal failure on the lipid and apolipoprotein concentrations of plasma, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) was studied in an experimental uremic rat model. Control rats were sham-operated and were divided into adlibitum-fed and pair-fed groups. The rats were studied (after an overnight fast) 32 days after the onset of uremia. The uremic rats had a 4-fold increase in plasma urea nitrogen and creatinine. The pair-fed and ad-lib-fed controls had similar levels of plasma urea nitrogen and lipid profiles. In the uremic rats, plasma triglyceride (TG) levels were increased 3.8-fold due to increased TG in the VLDL, IDL and HDL fractions. Their 2-3-fold increase in plasma free cholesterol (FC), esterified cholesterol (EC) and phospholipids (PL) were due to FC, EC and PL increases in VLDL, IDL, LDL and HDL. Their increase in plasma apo B (x 2.4) and apo E (x 1.5) were due to increases in VLDL, IDL and LDL. Their plasma apo A-I increased 2.4 fold due to increases in the LDL and HDL fractions. Uremic rats also had increases in the FC/PL molar ratio in VLDL, IDL and LDL. In their LDL, the apo B/total cholesterol (TC), apo B/PL and apo B/apo E molar ratios were decreased. In their HDL, the apo E/TC and apo E/PL molar ratios were decreased and the apo A-I/apo E molar ratio was increased. In conclusion, chronic uremia causes both quantitative changes in the levels and qualitative changes in the composition of the plasma lipoprotein particles. These results are compatible with the decreased hepatic lipase activities and impairment of remnant clearance observed in human chronic renal failure.

Animals↗

Glycogenesis and glyconeogenesis in skeletal muscle: effects of pH and hormones.

We examined the effects of selected hormones and pH on the rates of glyconeogenesis (L-[U-14C]-lactate----glycogen) and glycogenesis (D-[U-14C]glucose----glycogen) in mouse fast-twitch (FT) and slow-twitch muscles incubated in vitro (37 degrees C). Glyconeogenesis and glycogenesis increased linearly with increasing concentrations of lactate (5-20 mM) and glucose (2.5-10 mM), respectively, in both muscles. Glyconeogenesis was approximately three- to fourfold greater in the extensor digitorum longus (EDL) than in the soleus, whereas basal glycogenesis was twofold greater in the soleus muscle than in the EDL. Lactate accounted for up to 5% of the glycogen formed in the soleus and up to 32% in the EDL relative to the rates of glycogenesis (i.e., 5 mM glucose + 10 nM insulin) in each muscle. Corticosterone (10(-12)-10(-6) M) failed to alter glyconeogenesis, whereas this hormone reduced glycogenesis. Insulin (10 nM) markedly stimulated glycogenesis but failed to stimulate glyconeogenesis. The rates of both glycogenesis and glyconeogenesis were pH sensitive, with optimal rates at pH 6.5-7.0 in both muscles. Glyconeogenesis increased by 49% in the soleus and by 39% EDL at pH 6.5 compared with pH 7.4. Glycogenesis increased in the soleus (SOL) and EDL in the absence (SOL: +22%; EDL: +52%) and presence of insulin (SOL: +22%; EDL: +51%) at pH 6.5 when compared with pH 7.4. In additional experiments with the perfused rat hindquarter, rates of glyconeogenesis were shown to be highly correlated with proportion of FT muscle fibers in a muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dissociation between insulin binding and glucose utilization after intense exercise in mouse skeletal muscles.

Since there are data to indicate that heavy exercise decreases insulin binding to skeletal muscle at a point when glucose uptake is known to be augmented, we tested the hypothesis that insulin-stimulated glucose uptake and metabolism are dissociated from insulin binding after exercise. Therefore, insulin binding, 2-deoxy-d-glucose (2-DOG) uptake and glucose incorporation into glycogen and glycolysis were compared in soleus and EDL muscles of intensively exercised (2-3 h) mice and non-exercised mice. Basal 2-DOG uptake was increased in the exercised EDL (P less than 0.05) but not in the exercised soleus (P greater than 0.05). However, in both muscles intense exercise increased insulin-stimulated (0.1-16 nM) 2-DOG uptake (P less than 0.05). The rates of glycogenesis were increased in both the exercised muscles (P less than 0.05) as was the rate of glycolysis in the exercise soleus (P less than 0.05). Glycolysis was not altered in the EDL (P greater than 0.05). In the face of the increased 2-DOG uptake and glucose metabolism in the exercised muscles, insulin binding was not altered in the exercised soleus muscle (P greater than 0.05) and was decreased in the exercised EDL (P less than 0.05). These results indicate that after intense exercise there is a dissociation of insulin binding from insulin action on glucose uptake and metabolism in skeletal muscles.

Animals↗