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Biomedical subjects

P Chan

Publications and source records attributed to P Chan.

At least 127 records · Page 7Linked to original sources
PubMed1997

Thrombophilia in Patients with Hypertriglyceridemia.

Objectives: To investigate a possible relationship between hypertriglyceridemia and the coagulation system, a Cardiovascular Risk Factor Two-township Study was conducted in Taiwan. Design: A case-control study. This longitudinal, prospective study focused on the evolution of cardiovascular disease risk factors with emphasis on haemostatic factors. Subjects: Hypertriglyceridemic subjects (triglyceride <2.26 mmoll+1, n = 327) and age-matched normal controls from a population screening program. Main outcome measures: Haemostatic parameters measured in this study included prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors VIIc and VIIIc, and antithrombin-III and plasminogen levels. Results: In our male hypertriglyceridemic subjects, aPTT was not significantly reduced, while significant elevations of factor VIIIc, factor VIIc, and plasminogen and antithrombin-III levels were noted. In the female hypertriglyceridemic subjects, the elevation of factor VIIc, factor VIIIc, and plasminogen and antithrombin-III levels was highly-significant, whereas aPTT was not significantly reduced. Unexpectedly, the levels of the established coronary risk factor, fibrinogen, did not show a statistically different change. Similar to previous data, our hypertriglyceridemic subjects also presented with hyperinsulinemia, glucose intolerance, upper body obesity, and elevated blood pressure. Conclusions: Despite the fact that in population studies, triglycerides do not consistently appear to be an independent risk factor for coronary heart disease, our data suggest that a pronounced increase in triglycerides warrants aggressive therapy, because this increase may be associated with a hypercoagulable state. This phenomenon contributes another perspective to the study of higher cardiovascular mortality in hypertriglyceridemic subjects.

Journal Article↗
PubMed1997

Effect of trilinolein on superoxide dismutase activity and left ventricular pressure in isolated rat hearts subjected to hypoxia and normoxic perfusion.

Oxygen-derived free radicals have been implicated in the development of myocardial injury during hypoxia/reperfusion. Antioxidants can effectively inhibit the formation of free radicals and ameliorate the myocardial damage which may occur during hypoxia/reperfusion. Trilinolein is a triacylglycerol recently purified from the traditional Chinese medicinal plant Panax pseudo-ginseng. It has linoleic-acid residues as the only type of fatty acid residue in all three esterified positions of the triacyglycerol. It has been proposed that decreased endogenous superoxide dismutase (SOD) activity may contribute to free radical-mediated reperfusion injury of the ischemic myocardium. In the present study, when isolated rat hearts were subjected to hypoxia for 10, 30, 60 and 90 min without normoxic perfusion, a significant decrease in Mn-SOD activity was shown throughout the period of hypoxia, whereas the Cu.Zn-SOD activity was increased at 10 and 30 min but was not different from the baseline at 60 and 90 min of hypoxia. In rat hearts pretreated with 10(-7) mol/l trilinolein and subjected to 60 min of hypoxia without normoxic perfusion, Cu.Zn-SOD was augmented compared with baseline and compared with hearts subjected to 60 min of hypoxia without trilinolein, whereas Mn-SOD activity was still reduced compared with baseline, although less so than after 60 min of hypoxia without trilinolein. Pretreatment with trilinolein was associated with better preservation of left ventricular function during hypoxia and more rapid return to recovery during normoxic perfusion. This myocardial protective effect may be related to an antioxidant effect through potentiation of SOD, particularly Cu.Zn-SOD during hypoxia.

Animals↗
PubMed1997

Left ventricular filling profiles in young white-coat hypertensive patients without hypertrophy.

This study was to assess left ventricular diastolic function in young white-coat hypertensive subjects < 50 years of age without hypertrophy. Hypertensive patients (systolic or diastolic blood pressure > or = 140 or > or = 90 mm Hg on all three visits) were defined as white coat if their average 24-hour blood pressure was < 127/81 mm Hg and at least 18/16 mm Hg lower than their average office values. We chose three groups balanced for sex, age, and body mass index: 50 sustained hypertensives, 25 white-coat hypertensives, and 25 normotensives. Office blood pressure was similar in white-coat and sustained hypertensives. Ambulatory blood pressure was comparable in white-coat hypertensives and normotensives. Compared with normotensives, white-coat hypertensives had more impaired diastolic function: increased ratio of late to early filling velocities, raised ratio of late to early time-velocity integral, prolonged deceleration time, and lengthened isovolumic relaxation time (P<.001, P<.001, P=.002, and P<.001, respectively). No difference was noticed between white-coat and sustained hypertensives. Compared with normotensives, white-coat hypertensives had higher values of plasma and urine norepinephrine (P<.001 and P<.001, respectively), plasma and urine aldosterone (P<.001 and P=.002, respectively), plasma renin activity (P=.04), total cholesterol (P=.001), and LDL cholesterol (P<.001). No difference was observed between white-coat and sustained hypertensives. Within white-coat hypertensives, 24-hour urinary aldosterone closely correlated with the ratio of late to early filling velocities (P=.008), and plasma and 24-hour urinary norepinephrine correlated well with total cholesterol (P=.037 and P=.006, respectively). No correlation was detected within the sustained hypertensives and normotensives. Heightened neurohumoral activity clearly supported the progression of diastolic dysfunction and metabolic abnormality in white-coat hypertensives.

Adult↗
PubMed1997

(+)MK-801 does not prevent MPTP-induced loss of nigral neurons in mice.

The present study was designed to evaluate the effects of 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine [(+)MK-801] on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal damage in the mouse, with the goal of clearly defining what protective effects, if any, this noncompetitive N-methyl-phenyl-1,2,3,6-tetrahydropyridine receptor antagonist may have against MPTP neurotoxicity. Animals were treated with MPTP (40 mg/kg s.c.) and/or (+)MK-801 (3 x 1 mg/kg i.p. at 4-hr intervals starting 30 min before MPTP) and were killed at 8 hr and 1, 7 and 21 days after MPTP exposure. Dopamine concentrations were measured in the striatum and ventral mesencephalon, and the total number of neurons in the substantia nigra was estimated using an unbiased stereological technique. Administration of (+)MK-801 before MPTP temporarily prevented MPTP-induced dopamine depletion. This was observed at 8 hr in the striatum and 1 week in the ventral mesencephalon, but not at other time-points studied. In both areas of the brain, (+)MK-801 appeared to delay the elimination of the metabolite 1-methyl-4-phenylpyridinium ion without affecting its formation. A 30% loss of nigral neurons with tyrosine hydroxylase immunoreactive and cresyl violet staining was seen at 1 and 3 weeks in both groups of MPTP-exposed animals, regardless of whether they received (+)MK-801. These data suggest that (+)MK-801 may affect the acute pharmacological/biochemical events induced by MPTP, but it does not have any enduring protective effects on either dopamine concentrations and/or the cell loss induced by this neurotoxin in mice.

1-Methyl-4-phenylpyridinium↗
PubMed1997

Vascular calcification as a source of hand pain and weakness in a patient with end-stage renal failure.

This article describes a unique case of vascular calcification of the hands complicated by pain and weakness. The case demonstrates the interaction of the skeletal and renal systems and the consequences of an unrecognized imbalance of calcium and phosphorus metabolism. Definitive medical management to keep the calcium-phosphate product below 70 through the judicious use of aluminum phosphate binders and diet should be coordinated to prevent and limit the extent of these calcifications.

Calcinosis↗
PubMed1997

Highly successful long-term outcome of kidney transplantation in Chinese recipients: an enhancing race effect?

We report on 352 cadaveric kidney transplants and 294 living related transplants performed over a 25-yr period among the Chinese population of Hong Kong. There is a marked preference for transplanting male patients, especially from living donors, and we argue that this represents a cultural phenomenon within the Chinese population. The 10-yr graft survivals for related and cadaveric transplants are 86.2% and 67.4%, respectively. These figures are appreciably higher than corresponding figures in Caucasian populations. We show beneficial effects of using cyclosporin A, minimizing the cold ischemia time and avoiding very young and very old donors. There is a clear benefit of transplanting kidneys with zero or one mismatched HLA antigen against the recipient but no stepwise decrease in outcome as the number of mismatched antigens increases. There is close concordance between the outcome of living related grafts with zero, one, and two mismatched haplotypes against the recipient and no observable benefit of haplotype matching. We show that Chinese renal transplant recipients in other centers also have better long-term graft outcome than Caucasians, both for cadaveric and living related transplants. We draw attention to the existence of a detrimental "race effect" in other studies when Black recipients are compared with Caucasians and consider whether an enhancing race effect exists for Chinese or whether the better outcome reflects different underlying diseases in Chinese.

Actuarial Analysis↗
PubMed1997

Pyogenic myositis: caused by viridans streptococci in an adult with tetralogy of Fallot.

A 34-year-old man came to this Emergency Room because of fever, swelling and pain in the right thigh. Tetralogy of Fallot with bicuspid pulmonary valve was diagnosed after serial examination, and computed tomography of the right thigh revealed pyogenic myositis. Surgical drainage of the right thigh abscess and a further pus culture yielded viridans streptococci. There has been no record in the medical literature of a pyogenic myositis caused by viridans streptococci in an adult tetralogy of Fallot. This is thus the first case reported.

Adult↗
PubMed1996

Monoamine oxidase-dependent metabolism of dopamine in the striatum and substantia nigra of L-DOPA-treated monkeys.

The effects of monoamine oxidase (MAO) inhibitors on the metabolism of dopamine synthesized from exogenous L-DOPA were investigated in the striatum and substantia nigra of squirrel monkeys. Administration of a single dose of L-DOPA (methyl ester, 40 mg/kg, i.p.) caused a significant increase in the levels of dopamine, 3-4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and in the DOPAC/dopamine ratio in the putamen, caudate and substantia nigra. These changes were more pronounced in the substantia nigra than in the striatum and within the striatum of L-DOPA-treated monkeys, levels of dopamine and its metabolites were higher in the putamen than in the caudate nucleus. When L-DOPA treatment was preceded by the injection of clorgyline or deprenyl at a concentration (1 mg/kg) which selectively inhibited MAO A or MAO B, respectively, striatal dopamine was increased while the striatal DOPAC and HVA levels and DOPAC/dopamine ratio were significantly reduced as compared to the values obtained with 1-DOPA alone. The two MAO inhibitors also counteracted the increase in the DOPAC and HVA levels and DOPAC/dopamine ratio induced by L-DOPA in the substantia nigra. Thus, both MAO A and MAO B contribute to the metabolism of dopamine when higher levels of this neurotransmitter are generated from L-DOPA in the squirrel monkey. The extent of reduction of dopamine catabolism (as assessed by the decrease in DOPAC and HVA levels) in the striatum and substantia nigra was similar with clorgyline and deprenyl even if the ratio MAO A/MAO B was approximately 1 to 10. This indicates that, though catalyzed by both MAO A and MAO B, dopamine deamination following treatment with L-DOPA preferentially involves MAO A.

Animals↗
PubMed1996

Human skeletal myoblasts spontaneously activate allogeneic complement but are resistant to killing.

The complement (C) system has previously been implicated in several diseases of muscle. We here report that human myoblasts or rhabdomyosarcoma cell lines spontaneously activate C through the classical pathway, causing release of anaphylatoxins and coating of myoblasts with opsonic C fragments but without causing cell killing. Survival of myoblasts is a consequence of the abundant expression of the membrane C regulatory molecules MCP and CD59, and neutralization of CD59 renders cells susceptible to C killing. The decay-accelerating factor was expressed at a very low level. Myoblasts and rhabdomyosarcoma lines also abundantly express the fluid-phase regulators C1-inhibitor, factor H, C4 binding protein, S-protein, and clusterin and secrete a soluble form of CD59. Expression of membrane and fluid-phase regulators is enhanced by either IFN-gamma or TNF-alpha. Although myoblasts resist C killing, spontaneous activation of C on these cells may have important consequences in inflammatory diseases of muscle where the generation of anaphylactic and opsonic fragments will recruit and activate inflammatory cells. C activation on myoblasts may also have consequences for the use of these cells as vehicles for gene delivery. Inhibition of C using soluble complement receptor I (sCR1) efficiently protected myoblasts from C attack in vitro, and this agent, already being tested in therapy of several C-mediated diseases, might be of value in inflammatory muscle disease and in improving the efficiency of gene delivery.

Cell Death↗
PubMed1996

Identification and characterization of complement C3 receptors on human astrocytes.

Astrocytes express C components and have been implicated as a major source of intrathecal C. To ascertain the effects of C activation on these cells, we have evaluated the expression of CR1, CR2, and CR3 (CD35, CD21, and CD11b/CD18) in primary fetal astrocytes and astrocyte cell lines. None of the astrocyte cells tested expressed CR3, whereas primary astrocytes and one of four astrocyte cell lines expressed CR1 (220 kDa), as assessed at the protein and mRNA level. Primary fetal astrocytes and all four astrocyte cell lines expressed CR2 (155 kDa). Expression of CR2 by astrocytes was confirmed at mRNA level by reverse-transcriptase PCR, using different combinations of seven specific CR2 oligonucleotides, and by partial sequencing of the astrocyte CR2 cDNA. Astrocyte CR2 cDNA presented 100% homology with the lymphocyte CR2 cDNA between the position 181 bp to 600 bp and position 1017 bp to 1347 bp. An alternative splicing pattern of exon 11, reported previously in B cells, was observed in astrocyte CR2 cDNA. Astrocyte CR2 was functional, in that it specifically bound C3d and the EBV surface protein gp340, and the binding was blocked specifically with polyclonal anti-CR2. Scatchard analysis of membrane expression of CR2 on astrocytes revealed 2000 functional sites per cell with a Kd (3 x 10(-7) M) identical with that of CR2 on B cell (Raji).

Astrocytes↗
PubMed1996

Deprivation and cause specific morbidity: evidence from the Somerset and Avon survey of health.

OBJECTIVE: To investigate the association between cause specific morbidity and deprivation in order to inform the debates on inequalities in health and health services resource allocation. DESIGN: Cross sectional postal questionnaire survey ascertaining self reported health status, with validation of a 20% sample through general practitioner and hospital records. SETTING: Inner city, urban, and rural areas of Avon and Somerset. SUBJECTS: Stratified random sample of 28,080 people aged 35 and over from 40 general practices. MAIN OUTCOME MEASURES: Age and sex standardised prevalence of various diseases; Townsend deprivation scores were assigned by linking postcodes to enumeration districts. Relative indices of inequality were calculated to estimate the magnitude of the association between socioeconomic position and morbidity. RESULTS: The response rate was 85.3%. The prevalence of most of the conditions rose with increasing material deprivation. The relative index of inequalilty, for both sexes combined, was greater than 1 for all conditions except diabetes. The conditions most strongly associated with deprivation were diabetic eye disease (relative index of inequality 3.21; 95% confidence interval 1.84 to 5.59), emphysema (2.72; 1.67 to 4.43) and bronchitis (2.27; 1.92 to 2.68). The relative index of inequality was significantly higher in women for asthma (P < 0.05) and in men for depression (P < 0.01). The mean reporting of prevalent conditions was 1.07 for the most deprived fifth of respondents and 0.77 in the most affluent fifth (P < 0.001). CONCLUSIONS: Material deprivation is strongly linked with many common diseases. NHS resource allocation should be modified to reflect such morbidity differentials.

Adult↗
PubMed1996

Effectiveness and safety of low-dose pravastatin and squalene, alone and in combination, in elderly patients with hypercholesterolemia.

A double-blind, placebo-controlled study was conducted to compare the efficacy and safety of low-dose (10 mg) prevastatin and squalene (860 mg), either alone or in combination therapy, with placebo in the treatment of elderly patients with hypercholesterolemia. Ambulatory elderly patients (N = 102) were assigned in randomized fashion to receive active treatment or placebo for 20 weeks after a single-blind placebo lead-in period of 8 weeks. Total cholesterol and triglyceride levels in plasma were at least 250 mg/dL and less than 300 mg/dL, respectively. Concentrations of lipids and lipoproteins were measured, and clinical laboratory tests included liver function and creatine kinase determinations. Pravastatin 10 mg daily was more effective than squalene in reducing total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides and in increasing levels of high-density lipoprotein (HDL) cholesterol. Combination therapy significantly reduced total cholesterol and LDL cholesterol and increased HDL cholesterol to a greater extent than either drug alone. Adverse events and clinical laboratory abnormalities were generally mild and transient in all groups, and all but two patients finished the study. The incidence of side effects was low; myopathy did not occur. Coadministration of pravastatin and squalene combined the specific effects of the two drugs on lipoprotein concentrations. This combination may be useful and more cost-effective in elderly patients with hypercholesterolemia, who might have a higher incidence of side effects when using larger doses of pravastatin alone.

Aged↗
PubMed1996

Influence of Contraceptive Pill Use, Premenopause and Postmenopausal State on Hemostatic Parameters in Ethnic Chinese Women.

Background: Epidemiological studies has shown that increased fibrinogen and factor VIIc are two independent risk factors for cardiovascular disease (CVD). Postmenopausal women have a higher incidence of CVD than premenopausal women; one possible explanation is the increase of fibrinogen. Purpose: This study was undertaken to evaluate the influence of oral contraceptive pill use and postmenopausal status on coagulation factors in ethnic Chinese women. Patients and methods: This study included 1402 women aged 40-55 years, with 288 premenopausal women taking oral contraceptives and 364 postmenopausal women. All subjects underwent blood examination of prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIIc, factor VIIIc, plasminogen, and antithrombin III. Results: Data show that oral contraceptives users had a significant increase in plasminogen (91.7 +/- 40.7 vs. 80.0 +/- 26.5%; p < 0.01), while the levels of other hemostatic parameters were similar to non-contraceptive pill users. Postmenopausal women also had higher levels of plasminogen (113 +/- 36.2 vs. 108.7 +/- 30.7%; p = 0.06); the other parameters also show no statistical significance. Conclusions: Contrary to previous reports, which show elevation of fibrinogen and antithrombin III in menopause and in pill users, this study shows that only plasminogen levels exhibit a statistically significant contraceptive trend in Chinese women. Whether racial difference may account for the discrepancy in the present results needs further evaluation.

Journal Article↗
PubMed1996

The in vitro antioxidant activity of trilinolein and other lipid-related natural substances as measured by enhanced chemiluminescence.

There is abundant evidence for the premise that oxygen-derived free radicals (OFR) mediate ischemia/reperfusion injury to the myocardium. OFR scavengers such as superoxide dismutase can effectively reduce damage through lipid peroxidation during ischemia/reperfusion. Enhanced chemiluminescence, which has been used to measure OFR, was used to measure the antioxidant activity of fatty acids (palmitic and linoleic acid) and triglycerides (triolein, tristearin) and natural plant antioxidants (magnolol, catechin, trilinolein). Trilinolein, which has recently been isolated from natural products, as well as the well-known water soluble analogue of vitamin E-Trolox, were used as control. During pretreatment with chemicals, at concentrations of 10(-9) to 10(-7) M, enhanced chemiluminescence of linoleic acid (C 18:2) showed a dose-responsive reduction of OFR with a maximal mean reduction of -31.9% when compared to baseline. A saturated fatty acid such as palmitic acid (C 16:0) showed only relatively weak antioxidant activity at concentrations of 10(-7) to 10(-6) M with a maximum reduction of OFR of- 15.2% only. control chemicals such as trilinolein and Trolox showed significant antioxidant activity. At concentrations between 10(-10) and 10(-6) M and trilinolein has the most potent antioxidant activity with a maximal mean reduction of OFR of -48.0%, whereas Trolox showed only -39.2%. As for the natural plant antioxidants, only catechin showed potent antioxidant activity (-40%). Polyunsaturated triglycerides such as triolein (oleic acid, C 18:1) also possess significant OFR scavenging effect (-31.9%) whilst saturated triglycerides such as tristearin (stearic acid, C 18:0) had only relatively weak antioxidant activity (-15.2%). Generally, the antioxidant activity of unsaturated compounds is stronger than saturated compounds; double-bond existence may partially explain this phenomenon.

Antioxidants↗
PubMed1996

Thrombophilia in patients with hypercholesterolemia.

To investigate a possible interrelationship between hypercholesterolemia and the coagulation and fibrinolytic system, the Cardiovascular Disease Risk Factor Two-Township Study in Taiwan was undertaken as a longitudinal prospective study focusing on the evolution of cardiovascular disease risk factors, with an emphasis on hemostatic factors. Hemostatic parameters measured in this study included prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, factor VIIc, factor VIIIc, antithrombin III, and plasminogen. Subjects of both sexes with hypercholesterolemia (> 6.2 mmol/L) also had significant elevations of diastolic blood pressure, plasma glucose, triglycerides, fibrinogen, and factor VIIc and reduced PT and APTT compared with subjects with lower cholesterol. The hypercholesterolemic women additionally had significant elevations of systolic blood pressure and factor VIIc. Levels of the anticoagulant factors, antithrombin III and plasminogen, were also higher in both hypercholesterolemic men and women. In men, only factor VIIIc had no statistically significant elevation. In women, only PT showed no statistical difference. Established coronary risk factors such as fibrinogen and factor VIIc showed remarkable elevations in patients of both sexes. Using Pearson correlation and multiple regression, the most significant parameter related to cholesterol level was factor VIIc. The present results show that hemostatic abnormalities do exist in patients with hypercholesterolemia, and this thrombophilic phenomenon sheds further light on the study of higher cardiovascular mortality in these subjects.

Blood Pressure↗
PubMed1996

Trilinolein preserves mitochondria ultrastructure in isolated rat heart subjected to global ischemia through antioxidant activity as measured by chemiluminescence.

Oxygen-derived free radicals (OFR) have been proposed as the cause of myocardial damage through lipid peroxidation during ischemia and reperfusion. Antioxidants can effectively ameliorate the damage induced by lipid peroxidation. Trilinolein is a triacylglycerol recently purified from the well known traditional Chinese herb Panax pseudoginseng, which has been used in treating circulatory disorders among Chinese for hundreds of years; it has linoleate as the only fatty acid residue in all three esterified positions of glycerol. This chemical has recently been demonstrated to have antioxidant activity by enhanced chemiluminescence. The addition of phorbol myristic acetate (PMA) to medium containing leukocytes produces OFR; this phenomenon was measured by chemiluminescence. Addition of trilinolein to medium containing leukocytes preceding the addition of PMA suppressed the production of OFR. The control value of chemiluminescence of a medium containing leukocytes with addition of PMA was 9.23 +/- 1.19 x 10(3) mV. The most effective concentration of trilinolein was 10(-7) mol/l which decreased the signals to 4.59 +/- 0.02 x 10(3) mV (p < 0.001). The antioxidant effect had a concentration-response curve similar to alpha-tocopherol. After pretreatment for 15 min with trilinolein at a concentration of 10(-7) mol/l in isolated perfused rat heart which had been subjected to 60 min of global ischemia, the integrity of the rat heart mitochondria was preserved as examined under the electron microscope. No swelling of mitochondria occurred and there was good alignment of cristae and absence of amorphous density. Previous experiments have shown that trilinolein can also improve erythrocyte deformability in vitro. Infarct size reduction of about 50% was also demonstrated in in vivo rat heart subjected to 4 h coronary occlusion. The mechanism of myocardial protection, in addition to the antioxidant effect, is suggested as maintaining the membrane fluidity of cardiomyocytes.

Animals↗