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Biomedical subjects

P Chan

Publications and source records attributed to P Chan.

At least 145 records · Page 8Linked to original sources

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 Study drugs were withdrawn from one subject in each group with asymptomatic creatine kinase elevations.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↗

Spatial interference with vertical pistol sight alignment.

When competition pistol shooters aim, they perform four basic visual alignment tasks. With optimal stimuli such tasks can be performed with exquisite sensitivity. However, pistol sights and the target may not constitute the optimal stimuli, and this may impose limits on how well shooters perform. By simulating pistol sights and targets on a computer monitor, we investigated how the vernier task of aligning the top edges of the front and rear pistol sights was affected by the proximity of the target aiming mark. Alignment random error in this task, an analogous measure to vernier acuity, was unaffected by the proximity of the aiming mark; however, alignment systematic error did change significantly as the proximity of the aiming mark changed. This effect was unlikely to significantly change pistol shooting performance as shooters can adjust their sights to compensate for systematic errors. Likewise, compared to the vertical spread of shots on the pistol target, alignment random error was extremely small (only 10 s arc), which implies that other sources of variation limit pistol shooting performance.

Adult↗

Values of blood coagulating factors vary with ambient temperature: the Cardiovascular Disease Risk Factor Two-Township Study in Taiwan.

Seasonal influence on mortality from cardiovascular and cerebrovascular diseases is well documented. Understanding the seasonal variations in cardiovascular risk factors can shed light on this phenomenon. Elevation of coagulation factors during cold weather may in part explain the higher mortality from myocardial infarction and stroke in winter. The Cardiovascular Disease Risk Factors Community Study (CVDFACTS) included subjects belonging to 2 cohorts located in northern and southern Taiwan. This study included 2877 subjects aged 18 and above whose blood levels were examined for various coagulating factors. Besides measuring conventional cardiovascular risk factors including: blood pressure, body mass index and total cholesterol, values for blood fibrinogen, factor VII activity, factor VIII activity, plasminogen, antithrombin III, prothrombin time and activated partial thromboplastin time were determined for all subjects. Of these hemostatic parameters, levels of all, except prothrombin time, were statistically different between days with mean temperature > 20 degrees C and days with temperature < or = 20 degrees C (P < 0.01). In cold weather, a greater tendency to clot in circulatory system was demonstrated in this study, indicating seasonal variations may be demonstrated in this subtropical region.

Adult↗

Identification and characterization of the complement C5a anaphylatoxin receptor on human astrocytes.

The C fragment C5a exerts its important physiologic and pathologic effects through interaction with a specific C5a receptor (C5aR) which is highly expressed on polymorphonuclear leukocytes and some other leukocytes. The presence of this receptor on epithelia and endothelia has recently been documented, raising the possibility that these other cells might also respond to locally generated C5a. C has been implicated in several brain disorders, notably demyelination and neurodegeneration, and cells within brain can synthesize a complete C system. It is thus of interest to examine the mechanisms by which C damages or activates brain cells. To this end we have examined the expression on human fetal astrocytes and astrocyte-derived cell lines of receptors for C fragments. We here report that human astrocytes and cell lines express a receptor for C5a (48 to 72 x 10(3) copies/cell), which is indistinguishable at the protein or mRNA level from that in leukocytes. The astrocyte C5aR was recognized by five different specific Abs, which revealed by Western blotting a protein of 40 to 45 kDa in primary human astrocytes and astrocyte cell lines. Expression was confirmed by RT-PCR using multiple primers. Neither inflammatory cytokines nor PMA caused up-regulation of the receptor on astrocytes. The receptor was functional in that addition of C5a (1 nM to 100 nM) or, at high doses (100 nM), C5adesArg, triggered a calcium transient in astrocytes. We propose that C5aR expression on astrocytes plays an important role in control of inflammation in brain and may be a central component of C-mediated brain injury.

Amino Acid Sequence↗

Increased sympathetic nervous system activity in Chinese hypertensive patients with type II diabetes mellitus.

To evaluate the coexistence of sympathetic overactivity and hypertension in type 2 diabetic patients, a population-based study was conducted of newly-diagnosed type 2 diabetic patients recruited from a single community located at northern Taiwan. This study included 2877 (male 1382, female 1495) middle-aged ethnic Chinese adults, aged 45-65 years. Of the 1382 males, 67 had newly-diagnosed type 2 diabetes mellitus, whereas 75 of the 1495 females had type 2 diabetes. The data showed that about 39% of diabetic patients had borderline hypertension (mean blood pressure 141/91 mmHg) whereas the average incidence in non-diabetic subjects was 15.5%. The borderline hypertensive diabetic patients had significantly higher heart rates (mean 78.8 vs. 69.3 beats/min; P < 0.001) than control subjects. However, the cardiac index was similar in both control and diabetic subjects (mean 2.48 vs. 2.53 l/min/m2; P > 0.05). Our data show that sympathetic overactivity and increased incidence of hypertension actually existed in these type 2 diabetic patients of Chinese origin.

Analysis of Variance↗

The three heavy-chain precursors for the inter-alpha-inhibitor family in mouse: new members of the multicopper oxidase protein group with differential transcription in liver and brain.

The inter-alpha-inhibitor (I alpha I) family is comprised of the plasma protease inhibitors I alpha I, inter-alpha-like inhibitor (I alpha LI), pre-alpha-inhibitor (P alpha I) and bikunin. I alpha I, I alpha LI and P alpha I are distinct assemblies of bikunin with one of three heavy (H) chains designated H1, H2 and H3. These H chains and bikunin are respectively encoded by a set of three H genes and an alpha 1-microglobulin/bikunin precursor (AMBP) gene. All four gene products undergo maturation steps from precursor polypeptides. The full-length cDNAs for the H1-, H2- and H3-chain precursors were cloned from a mouse liver cDNA library and sequenced. Extensive searches of amino acid sequence similarities to other proteins in databanks revealed (i) a highly significant similarity of the C-terminal sequence in the three H-chain precursors to the multicopper-binding domain in the group of multicopper oxidase proteins and (ii) the presence of von Willebrand type-A domains in the mature H chains. Amino acid sequence comparisons between the three mouse H1-, H2- and H3-chain precursors and their human counterparts allowed us to appraise the timing and order of occurrence of the three H-chain genes from a shared ancestor during mammalian evolution. Owing to a multiple alignment of the six mouse and human nucleotide sequences for these H-chain precursors, a reverse transcriptase PCR assay with degenerate oligonucleotides was designed, allowing us to (i) present evidence that no mRNAs for further H genes exist in mouse liver and (ii) demonstrate a previously undescribed transcription of the H2- and H3-chain mRNAs in mouse brain, which contrasts with the expression of all four, H1, H2, H3 and AMBP, mRNAs in liver.

Alpha-Globulins↗

The effectiveness and safety of low dose pravastatin in elderly hypertensive hypercholesterolemic subjects on antihypertensive therapy.

To evaluate the efficacy and safety of low dose (10 mg) pravastatin in hypercholesterolemic, hypertensive elderly subjects undergoing antihypertensive treatment, a randomized, double-blind, placebo-controlled 6-month trial was conducted. The subjects had a total plasma cholesterol 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). Sixty elderly hypertensive patients randomly received placebo (n = 30) or pravastatin (n = 30) treatment. The dosage consisted of 10 mg of pravastatin daily during the 6-month trial. Over that period, in the pravastatin group, plasma levels of total cholesterol and LDL-cholesterol significantly (P < .01) dropped (-20% and -25%, respectively) compared to the placebo group. The plasma level of HDL-cholesterol increased (+5%) while triglycerides slightly decreased (-8%) (P < .05). No serious side effects occurred, and pravastatin was generally tolerated. Fasting hyperinsulinemia (11.0 +/- 0.8 v 9.3 +/- 0.7 microU/mL; P = .06) also improved, although not significantly, after 6 months of pravastatin therapy. Results from this study confirmed that a low dose (10 mg) of pravastatin daily is a safe and effective method of reducing plasma total and LDL-cholesterol in hypercholesterolemic, hypertensive elderly patients who are on concurrent antihypertensive drug therapy.

Aged↗

Venous hemodynamic abnormalities in patients with leg ulceration.

PURPOSE: Venous ulceration in the leg has been predominantly associated with deep venous insufficiency, although a few reports have implicated the superficial veins. The aim of this study was to identify the distribution of valvular incompetence in patients with active leg ulceration. PATIENTS AND METHODS: Color flow duplex imaging (CFDI) ultrasonography was used to evaluate the entire venous system--superficial, perforator and deep--from groin to ankle in 112 limbs of 94 patients with venous leg ulcers. RESULTS: Seventy two limbs (64%) had multisystem incompetence and 36 (32%) had one system involved only, whereas in 4 limbs (4%) there was no venous incompetence. Deep venous reflux exclusively was present in 7 limbs (6%) and the perforator system alone was involved only in 3 limbs (3%). However, isolated superficial incompetence was seen in 26 extremities (23%) and combination of superficial with perforator system alone in 23 (21%). In addition, reflux overall in the superficial system (alone and in combination with perforator and deep systems) was seen in 94 limbs (84%). The most common pattern (28%) of abnormality was reflux in all systems, superficial, perforator, and deep. CONCLUSIONS: The results of this study show that variable combined patterns account for over two thirds of patients with ulceration. No comprehensive surgical policy for alleviating ulceration can be justified; we suggest that a complete evaluation of all venous systems from groin to ankle with CFDI ultrasonography in patients with venous ulceration is practical on a routine basis and will be particularly valuable before surgery in order to target intervention at specific incompetent sites.

Adolescent↗

Salmonellosis and mycotic aneurysm of the aorta. A report of 10 cases.

We report a 5 year experience of 10 cases of mycotic aneurysms of the aorta caused by salmonella infection. Of the 10 patients, nine were males and one was female in an age range from 60 to 80 years with a mean of 71 years. The major clinical manifestations were fever, abdominal or back pain, pulsatile abdominal mass and leucocytosis. The diagnosis was based on clinical symptoms and signs and positive blood or tissue cultures. The main confirmatory procedure was computed tomography (CT). Two year survival rate was 20%. Five patients died during hospitalisation, without surgery. Three patients died within 2 months of surgery. The other two patients, treated surgically and by intensive antibiotic therapy, survived. Death resulted usually from recurrent infection and graft leakage. Contrary to previous reports, salmonella mycotic aneurysm is still common in this geographical area and the prognosis is poor.

Aged↗

Photodynamic therapy in a cell culture model of human intimal hyperplasia.

OBJECTIVE: To investigate the effectiveness of photodynamic therapy (PDT) in eliminating proliferating vascular smooth muscle cells (VSMCs). This may have a potential role in reducing restenosis rates clinically. MATERIALS AND METHODS: Human VSMCs were successfully cultured from 15 long saphenous veins (SV) and seven restenotic lesions (RL) removed during revision coronary and peripheral vein graft surgery. Cultured VSMCs were incubated with photofrin at doses of 0-5 micrograms/ml for 48 h, and then exposed to 4 J/cm2 of polychromatic light. Cell destruction was quantified by a colorimetric assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. RESULTS: Results are expressed as a mean percentage survival +/- standard error. Cells were minimally affected by either photofrin alone (SV: 95.5% +/- 5.3; RL: 119.8 +/- 4.8) or light alone (SV: 75.38% +/- 3.99; RL: 100.1 +/- 11.0). The combination of 2 micrograms/ml of photofrin and 4 J/cm2 of polychromatic light energy, i.e. PDT, was severely toxic to cells derived from saphenous veins (5.52% +/- 0.85) as well as cells derived from restenotic lesions (9.6 +/- 2.3). These doses are comparable to doses that can be achieved in vivo. CONCLUSION: PDT in the appropriate drug and light doses can eliminate human VSMCs, including those responsible for vascular restenosis.

Cell Division↗

Colour flow duplex scanning in suspected acute deep vein thrombosis; experience with routine use.

OBJECTIVES: To determine the accuracy of colour flow Duplex scanning (CFDS) in the diagnosis of deep vein thrombosis (DVT) and subsequently to investigate its diagnostic value in patients who have normal deep veins despite symptoms. DESIGN: Prospective open clinical study. SETTING: Vascular laboratory and radiology departments of University Hospital. MATERIALS AND METHODS: In the first part 112 limbs in 103 patients, 94 with symptoms of acute DVT and nine with pulmonary embolism (PE) were examined prospectively with CFDS and venography. Subsequently, in the second part, 328 legs in 304 patients were examined by CFDS alone for acute symptoms of DVT or PE. MAIN RESULTS: DVT was detected in 55 limbs by venography: proximal DVT was seen in 23 limbs, distal DVT in 25 limbs and both proximal and distal in seven limbs. CFDS was 100% sensitive and 98.8% specific in detecting proximal DVT whereas its sensitivity and specificity was 87.5% and 98.7% for distal DVT. Positive and negative predictive values were over 95% for both limb segments. The overall accuracy for the proximal DVT was 99.4% and for the distal 93.1%. In the second part, CFDS alone detected DVT in 156 limbs (47.6%); DVT was in the proximal segment in 82, distal segment in 61 and both in 13. In 172 limbs other causes of symptoms were identified in 34 (20%). CONCLUSIONS: We have demonstrated that CFDS is as accurate as venography when used by experienced operators. The average time of examination is 15-20 minutes and compares favourably with venography. Other causes of leg symptoms can also be diagnosed by CFDS in around 20% of patients who are found to have normal veins.

Humans↗

Inhibition of human vascular smooth muscle cell proliferation by the novel multiple-action antihypertensive agent carvedilol.

We examined the antiproliferative effect of the novel multiple-action antihypertensive agent carvedilol on human vascular smooth muscle cells (VSMC). Carvedilol inhibited the increase in cell number induced by foetal calf serum (FCS) in 86% (18 of 21) of human VSMC grown both from saphenous vein (17.6 +/- 3.5% inhibition, mean +/- SEM, n = 15) and restenotic lesions (31.4 +/- 5.5% inhibition, mean +/- SEM, n = 5). Carvedilol had a greater antiproliferative effect than other beta-adrenoceptor antagonists. In comparison with calcium channel blockers, carvedilol (10 microM) elicited a degree of growth inhibition similar to that of verapamil, but was less effective than the dihydropyridine amlodipine at equimolar concentrations. Although carvedilol had a greater antiproliferative effect on cells derived from restenotic lesions cells than on control saphenous vein cells, the difference was not statistically significant. In the present study, the antiproliferative effect of carvedilol on human VSMC in vitro occurred at concentrations higher than those in plasma. Although this may represent a limitation to the clinical efficacy of carvedilol against proliferation of VSMC associated with hypertension and atherosclerosis, the apparent relative selectivity of carvedilol for restenosis-derived cells is a promising line of investigation.

Antihypertensive Agents↗

Coagulation activation in type 2 diabetes mellitus: the higher coronary risk of female diabetic patients.

Thrombophilia in diabetic patients is a well-recognized phenomenon which constitutes an additional risk of coronary heart disease. This study included 1980 ethnic Chinese people (835 male, 1145 female); age range: 45 to 69 years, including 280 Type 2 diabetic patients (male 125, female 155). Haemostatic parameters measured were fibrinogen, prothrombin time, activated partial thromboplastin time (APTT), factor VIIc, factor VIIIc, antithrombin III, and plasminogen. Compared with a control group, male diabetic patients showed significantly shorter APTT (25.6 +/- 3.7 vs 27.5 +/- 3.6 s, p < 0.001), and elevated factor VIIIc (171.1 +/- 77.48 vs 131.16 +/- 52.23%, p < 0.0001), whereas female diabetic patients showed significantly shorter APTT (24.9 +/- 4.2 vs 26.5 +/- 3.9 s, p < 0.001) and elevated fibrinogen (10.6 +/- 3.3 vs 9.8 +/- 2.6 mumol 1(-1), p < 0.05), factor VIIc (150.4 +/- 68.7 vs 135.3 +/- 32.3%, p < 0.001), factor VIIIc (190.1 +/- 92.6 vs 141.1 +/- 62.4%, p < 0.0001), and plasminogen (140.3 +/- 41.9 vs 128.4 +/- 38.7%, p < 0.01). This study showed that Chinese diabetic patients had coagulation activation, and that female diabetic patients seemed to constitute a higher risk group for coronary heart disease than males.

Aged↗