Adolescent polycystic ovary syndrome.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
P Chan
Publications and source records attributed to P Chan.
Short-term safety and efficacy of low-dose simvastatin in elderly patients with hypertensive hypercholesterolemia and fasting hyperinsulinemia.
To evaluate the short-term safety and efficacy of low-dose (10 mg) simvastatin in hypercholesterolemic, hypertensive elderly Chinese patients receiving antihypertensive treatment, a randomized, double-blind, placebo-controlled, 3-month trial was conducted. The patients had a total plasma cholesterol level of at least 250 mg/dL and had been, for at least 3 months, consuming a standard lipid-lowering diet (American Heart Association Step 1 Diet). Elderly hypertensive patients (n = 76) were randomized to receive treatment with either placebo (n = 38) or simvastatin (n = 38). The dosage consisted of 10 mg simvastatin daily during the 3-month trial. During that period, in the simvastatin group, plasma levels of total cholesterol and low-density lipoprotein cholesterol decreased significantly (27% and 33%, respectively) compared with those levels in plasma in the placebo group. The plasma levels of high-density lipoprotein cholesterol increased (7%), whereas triglyceride levels slightly decreased (8%). There were no serious side effects, and simvastatin was generally well tolerated. Fasting hyperinsulinemia also improved (-21%) after 3 months of simvastatin therapy. Results of this study confirmed that a low dose (10 mg) of simvastatin daily is a safe and effective method of reducing plasma levels of total and low-density lipoprotein cholesterol in hypercholesterolemic, hypertensive elderly patients receiving concurrent antihypertensive drug therapy, and that it has the additional potential benefit of reducing plasma levels of insulin.
Aged↗
Double-blind comparison of losartan, lisinopril, and metolazone in elderly hypertensive patients with previous angiotensin-converting enzyme inhibitor-induced cough.
This study compared the incidence of cough with the angiotensin-converting enzyme (ACE) inhibitor lisinopril and the diuretic metolazone with angiotensin II receptor antagonist losartan in elderly hypertensive patients with previous histories of ACE inhibitor-induced cough. A randomized, double-blind, stratified, parallel-group comparison of lisinopril at 10 mg, losartan at 50 mg, and metolazone at 1 mg, each given once daily for a maximum of 10 weeks, was performed in four hypertension clinics in four centers in two countries. Cough was detected by a questionnaire (the primary end point) given to elderly patients with hypertension, and the cough frequency was quantified by a visual analog scale (a secondary end point). A total of 84 elderly patients with hypertension, all who were nonsmokers with ACe inhibitor-induced cough and were confirmed by lisinopril rechallenge then placebo dechallenge, were randomized to the three treatment groups. The incidence of cough with losartan (18%) was significantly lower than with lisinopril (97%) and similar to that for metolazone (21%). Cough frequency evaluated by the visual analog scale was significantly lower for losartan than for lisinopril and similar to that for metolazone. The specific, selective angiotensin II receptor antagonist losartan is associated with a decrease in the incidence of cough in patients with previous ACE inhibitor-induced cough.
Aged↗
Surface expression of low density lipoprotein receptor in EBV-transformed lymphocytes: characterization and use for studying familial hypercholesterolemia.
The objectives of the present study were to characterize the surface expression of low density lipoprotein receptor (LDL-R) in Epstein-Barr virus transformed lymphocytes (EBV-L) and to determine the applicability of the cellular system for the study of familial hypercholesterolemia. The EBV-L subsets and LDL-R expression were determined by immuno-cytofluorimetry. The LDL-R expression in EBV-L which consisted of mostly B cells was no different among antigenic subsets. EBV-L cultured in lipoprotein deficient serum demonstrated a 9.3-fold higher LDL-R expression than primary lymphocytes. Lovastatin caused an additional 1.9-and 1.4-fold increase in EBV-L and primary lymphocytes respectively. This difference in lovastatin response is statistically significant (paired t-test, P < 0.001). 54% of the high LDL-R expression in EBV-L was related to the changes in proliferation measured as stimulation index (SI). LDL and lovastatin modulated the LDL-R expression without affecting SI. FH subjects demonstrated 2% (homozygote, n = 1) and 44.6 +/- 12.3% (heterozygotes, n = 35) in LDL-R expression of controls (n = 30). This maintenance of the FH phenotype and the intrinsically high LDL-R expression in EBV-L make the cellular system suitable for the study of FH as well as the regulation of LDL-R.
Adolescent↗
Additive effects of diltiazem and lisinopril in the treatment of elderly patients with mild-to-moderate hypertension.
A multicenter, double-blind, placebo-controlled trial with multifactorial design was conducted to evaluate the safety and efficacy of the calcium-channel blocker diltiazem, in a sustained release preparation, and the angiotensin converting enzyme inhibitor, lisinopril, in the treatment of elderly Chinese patients with mild-to-moderate hypertension. In addition to the hypotensive effects of combinations of both drugs compared with monotherapy, all given once daily, the effect on quality of life was also evaluated. This study consisted of a 3 x 2 multifactorial design in which 156 women and men with a sitting diastolic pressure of between 95 mm Hg and 114 mm Hg, after a 4-week placebo washout phase, were randomized to one of six treatment groups for 12 weeks of active treatment. Monotherapy with diltiazem 120 or 240 mg produced increasing reductions of systolic and diastolic blood pressure. Compared with placebo, lisinopril 10 mg had an effect intermediate between the diltiazem doses. The combinations of diltiazem 240 mg + lisinopril 10 mg and diltiazem 120 mg + lisinopril 10 mg showed increased efficacy in reducing systolic and diastolic blood pressure compared to these drug doses used in monotherapy, but the effect of the combinations was less than predicted by an additive model. Although the total number of other adverse events reported was similar for all active treatment groups compared to placebo, lisinopril-induced cough was common with an incidence of 31% after rechallenge. Premature drug withdrawal was necessary in four of 78 patients receiving lisinopril, due to intractable cough. The combination of diltiazem 240 mg and lisinopril 10 mg was significantly more effective at reducing blood pressure than either drug alone; this additive effect did not result in a higher rate of adverse effects or impairment of quality of life. Thus, combination therapy with these agents was well tolerated and resulted in increased efficacy in these elderly patients.
Aged↗
Prospects for prevention of graft stenosis and angioplasty restenosis.
Explore the source record for details and available documents.
Angioplasty, Balloon, Coronary↗
(+)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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
Beneficial effects of pravastatin on fasting hyperinsulinemia in elderly hypertensive hypercholesterolemic subjects.
We undertook this prospective double-blind, placebo-controlled study to evaluate the efficacy and safety of low-dose (15 mg) pravastatin in elderly hypercholesterolemic hypertensive subjects with concurrent antihypertensive treatment and to determine whether fasting hyperinsulinemia could also be improved. At three hypertension and lipid clinics of two medical centers, 96 elderly (49 women, 47 men) ambulatory subjects were randomized to active treatment or placebo for 12 months after a 3-month single-blind lead-in period. Hypertensive subjects with plasma total cholesterol levels of at least 6.47 mmol/L (250 mg/dL) and triglyceride levels less than 3.39 mmol/L (300 mg/dL) were treated with 15 mg pravastatin for 12 months after receiving 3 months of the American Heart Association step I diet. Lipid, glucose, and fasting insulin levels were measured; clinical laboratory tests included liver function and creatine kinase determinations. After 12 months of pravastatin therapy, plasma total cholesterol concentration decreased by 25.1% (from a mean of 7.29 to 5.47 mmol/L, P < .05), low-density lipoprotein cholesterol decreased by 30.2% (from 5.27 to 3.68 mmol/L, P < .05), and triglycerides decreased by 10.7% (from 1.68 to 1.50 mmol/L, P < .05). High-density lipoprotein cholesterol increased by 9.2% (from 1.20 to 1.31 mmol/L, P < .05). Fasting insulin levels decreased from 89.0 to 61.5 pmol/L (P < .05). All of these changes were greater (P < .05) than any tendency toward change in the placebo group. Adverse events and clinical laboratory abnormalities were generally mild and transient in both placebo and pravastatin groups. Study drugs were withdrawn from one subject in each group with asymptomatic creatine kinase elevations. We conclude that low-dose pravastatin was effective and safe in the treatment of hypercholesterolemic hypertensive subjects on concurrent antihypertensive therapy. It also improved fasting hyperinsulinemia despite the use of beta-blockers and diuretics in these hypertensive subjects.
Aged↗