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Biomedical subjects

Kiat T Tan

Publications and source records attributed to Kiat T Tan.

16 recordsLinked to original sources
PubMed2006

CT diagnosis of coronary artery aneurysms.

Most coronary artery aneurysms are caused by either atherosclerosis or Kawasaki Disease. These lesions can potentially rupture or cause thromboembolic complications. Traditionally, coronary artery aneurysms are diagnosed by conventional coronary angiography. However, as CT coronary artery angiography has been shown to be useful in the visualisation of the larger blood vessels, this imaging modality may well replace conventional angiography as the investigation of choice in the diagnosis of coronary artery aneurysms. Indeed, we present an example where CT coronary angiography has proved useful in the characterisation of the disease.

Coronary Aneurysm↗
PubMed2006

Platelet microparticles and platelet adhesion: therapeutic implications for the prevention and treatment of stroke.

Platelets are believed to play a part in all stages of the pathogenesis of ischemic stroke, from the initial formation of the atherosclerotic plaque, through plaque destabilization to the development of neuronal cell death. A process common to all of these pathogenic changes is the ability of the activated platelet to adhere to the site of disease. In addition, the release of the membrane vesicles from platelets enhances many of these processes. Therefore, an understanding of platelet adhesion and platelet microparticle release can aid the development toward the treatment and prevention of stroke. There has been much research into interventions that can reduce platelet activation in atherosclerosis and stroke. The benefits of nonpharmacologic interventions in stroke, such as diet and lifestyle modification, may in part be mediated by their effects on platelet activation. In addition, the antiplatelet drug aspirin has been shown to be useful in both the treatment of acute stroke and the secondary prevention of atherothrombosis. Other antiplatelet agents, such as the glycoprotein IIb/IIIa inhibitors and triflusal, are currently being evaluated for the treatment of acute atherothrombotic stroke.

Journal Article↗
PubMed2005

Plasma matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-2, and CD40 ligand levels in patients with stable coronary artery disease.

Endogenous matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitor of metalloproteinases (TIMPs), are important mediators of extracellular matrix remodeling, which is integral to plaque progression in coronary artery disease. In addition, high levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. We hypothesized that circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were abnormal in patients who had stable coronary artery disease, and these levels were compared with those in matched controls. We also hypothesized correlations of MMPs, TIMPs, and sCD40L to each other and to high-sensitivity C-reactive protein (a proinflammatory marker), white blood cell count, severity of coronary artery disease (based on angiographic measurements of atherosclerotic burden), and coronary collateralization. We studied 204 adult patients who attended our unit for outpatient diagnostic cardiac catheterization for the investigation of suspected coronary artery disease. Coronary angiograms were scored for atheroma burden and stenosis by 2 independent observers. Circulating levels of MMP-9, TIMP-1, TIMP-2, and sCD40L were measured by enzyme-linked immunosorbent assay. Plasma levels of MMP-9 (p = 0.0099), TIMP-2 (p = 0.0019), and sCD40L (p <0.001), but not TIMP-1 (p = 0.463) were high in patients compared with healthy controls. In patients who had coronary artery disease, MMP-9 and high-sensitivity C-reactive protein levels were significantly higher in women than in men. Only MMP-9 correlated modestly with total white blood cell count (Spearman's correlation, r = 0.274, p = 0.002). Logistic regression of cardiovascular risk factors showed that only white blood cell count was independently associated with MMP-9 (p = 0.02). After standardizing for atheroma and stenosis scores, there were no statistically significant differences in our research indexes in patients who had angiographic collaterals compared with those who did not. In conclusion, stable coronary artery disease is associated with abnormal circulating levels of MMP-9, TIMP-2, and sCD40L, which do not appear to related to each other or to severity of coronary artery disease or collateralization. The gender difference in high-sensitivity C-reactive protein and MMP-9 levels may provide insight into the pathophysiology of coronary artery disease in men and women, and further studies are warranted to explore this potential link.

Aged↗
PubMed2005

Relation of platelet activation to coronary angiographic severity and collateralization.

We investigated whether platelet activation can be correlated with angiographic severity and the degree of collateralization in coronary artery disease (CAD), as well as endothelial damage/dysfunction. No studies have attempted to correlate platelet activation status, as measured by soluble plasma markers (soluble CD40 ligand, soluble P-selectin, soluble glycoprotein V), with the appearance of diseased coronary arteries. We found evidence of increased platelet activation in CAD, but a lack of correlation between the degree of platelet activation and the angiographic disease severity, which may reflect the presence of disease elsewhere or the presence of coronary atheroma not detected by angiography.

Aged↗
PubMed2005

Elevated platelet microparticles in stable coronary artery disease are unrelated to disease severity or to indices of inflammation.

Platelet microparticles (PMPs), procoagulant membrane vesicles derived from activated platelets, are elevated in acute myocardial infarction and unstable angina but their relationship to inflammation and indices of coronary artery disease are unclear. We therefore hypothesised that PMPs are related to scores of coronary atheroma and/or coronary stenosis. Our study was completed by comparing PMP data with other platelet markers and with hs-CRP, marking inflammation. We recruited 54 patients attending for coronary angiography, comparing them to 35 age- and sex-matched controls. Peripheral blood was analysed for PMPs, percent platelets positive for CD62P and CD63 (all flow cytometry), soluble P selectin and hsCRP (both immunoassay). Patients exhibited higher PMPs, increased platelet %CD62P, %CD63 and soluble P selectin (all P < 0.01) and hs-CRP (P = 0.0167) than healthy controls. However, analysing only patients with an unequivocal classification, there were no significant (P </= 0.01) correlations with coronary atheroma or coronary stenosis. These findings provide no support for the hypothesis that PMPs are related to the degree of coronary artery disease and therefore may simply be a marker of widespread inappropriate platelet activity.

Aged↗
PubMed2005

Platelet microparticles and soluble P selectin in peripheral artery disease: relationship to extent of disease and platelet activation markers.

BACKGROUND: There is increased platelet activation in many cardiovascular diseases. This observation may explain the presence of increased levels of platelet microparticles (PMP) in these diseases. However, whether or not levels of PMPs inter-relate with other markers of platelet activation, such as soluble P-selectin, or with disease severity, is unknown. We therefore hypothesized raised PMP levels in stable peripheral artery disease (PAD) intermittent claudication (IC), with an additional increase in severe PAD critical limb ischaemia (CLI). Furthermore, we tested the hypothesis that PMP levels are correlated with other markers of platelet activation, such as soluble P-selectin, membrane bound P-selectin (CD62P) and 63. METHODS: Patients with PAD were recruited from the vascular outpatient and inpatient facilities at a teaching hospital. Age- and sex-matched controls were also recruited from healthy volunteers. Venous blood was obtained from 23 patients with severe disease (CLI), 36 with moderate disease (IC), and from 30 healthy controls. The percentage of platelets positive for CD62P and CD63, as well as the numbers of PMPs were defined by flow cytometry. Plasma soluble P selectin was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: PMPs were increased relative to healthy controls in patients with IC, with a further increase in CLI (P<0.001). Soluble P selectin and CD62+ve platelets were raised in both patient groups, but there was no difference amongst the two patient groups. CD63+ve cells were raised only in CLI compared to healthy controls. In multivariate analysis, only PMP and soluble P selectin independently predicted disease severity, and the two markers correlated modestly (r=0.345, P<0.001). CONCLUSION: Increased PMP and soluble P selectin are both related to the severity of symptomatic PAD. However, it is uncertain if this relationship is a cause or effect of atherosclerosis. This finding may have clinical implications as PMPs have the potential to influence the progression of atheroma as well as promote thrombosis.

Aged↗
PubMed2005

Soluble CD40L in peripheral artery disease. Relationship with disease severity, platelet markers and the effects of angioplasty.

Although soluble CD40L (sCD40L, possibly derived from platelets and pro-inflammatory in vitro) may be implicated in thrombosis and haemostasis, there are little data in peripheral artery disease (PAD). We hypothesised the following: (a) that sCD40L relates to the clinical severity of PAD; and (b) that peripheral artery angioplasty acutely raises sCD40L levels. sCD40L was compared to established platelet markers soluble P selectin, platelet microparticles and platelet surface expression of CD62 and CD63. We recruited 36 healthy controls, 33 patients with intermittent claudication (IC), and 33 with symptomatically more severe critical limb ischaemia (CLI), measuring plasma markers by ELISA and membrane markers by flow cytometry. Eleven patients with CLI subsequently underwent peripheral artery angioplasty: blood was taken before and 10 minutes after the intervention. Results show that sCD40L was raised in IC at median 68 (IQR 28-333) pg/ml and in CLI at 64 (34-282) pg/mL compared to 35 (IQR 28-55) pg/ml in the healthy controls (p=0.009). Levels were no different between IC and CLI. The same distribution pattern was present for soluble P selectin, %platelets CD62+ve and CD63+ve. sCD40L failed to correlate significantly with ABPI (p=0.264), unlike %platelets CD62+ve (p=0.0032) and CD63+ve (p=0.009). Pre-angioplasty sCD40L level of 72 (35-610) ng/ml rose to 100 ng/ml (IQR=60-237)(p=0.018) post-angioplasty. Plasma sCD40L, in addition to other platelet indices, is raised in peripheral atherosclerosis and is increased by peripheral artery angioplasty, although levels seem unrelated to clinical severity. Failure to correlate with other markers suggest the platelet may not be the sole source of sCD40L, and that other cells may contribute to plasma levels.

Aged↗
PubMed2005

The potential role of platelet microparticles in atherosclerosis.

The release of microvesicles ('platelet microparticles', PMPs) by activated platelets has been shown to be an integral part of the thrombotic process. PMPs are believed to mediate many biological processes as they possess various platelet membrane proteins and bioactive lipids. Of note, there is a growing body of evidence that PMPs are involved in all stages in the pathobiology of atherosclerosis. In addition to their role in thrombosis, PMPs may also have a pro-inflammatory effect, which promotes the development of atherosclerosis. Also, bioactive lipids in PMPs have been shown to have important effects on angiogenesis. This review summarises the various studies on the possible role of PMPs in the progression of atherosclerosis.

Animals↗
PubMed2005

The assessment of platelet activation in antiplatelet drug development.

Platelet activation plays an important role in a wide range of pathological conditions. For example, platelet activation has been shown to be involved in the defence against parasitic infection, the pathogenesis of atherosclerotic disease, and various arterial and venous thrombotic diseases. Indeed, there is considerable interest in the manipulation of platelet function for therapeutic gain. It is for these reasons that there is considerable interest in developing assays measuring in vivo platelet activation. Current modalities in the measurement of platelet activation include Enzyme-linked Immunosorbent Assays (ELISA), platelet flow cytometry and electron microscopy. It is proposed that methods in measuring platelet activation can also be classified into 'direct' and 'indirect' modalities, both of which have their distinct advantages and disadvantages. Unfortunately, there is at present no consensus on the ideal method of measuring platelet activation. Thus, studies on platelet activation should ideally include at least one of each of direct and indirect modality of studying platelet activation. This review provides an overview of basic platelet biology and the various methods of measuring platelet activation, with an emphasis on their role in drug development.

Animals↗
PubMed2005

Fondaparinux.

Fondaparinux is the first drug from the pentassaccharide factor X inhibitor class of anticoagulants to be approved for clinical use. It has been shown to be effective in the prevention of deep vein thrombosis in patients undergoing major orthopaedic surgery of the lower limbs. The drug is also being evaluated for use in the acute coronary syndromes and established thromoboembolic events. The pharmacology of fondaparinux is discussed in this review, as well as the major clinical trials involving this drug. Arguments for (and against) the use of this drug are also summarised.

Anticoagulants↗
PubMed2003

Post-stroke inflammatory response: effects of stroke evolution and outcome.

Recovery after stroke is often hindered by further neurologic deterioration, which can affect up to 45% of patients. It has been suggested that one of the major causes of this neurologic deterioration may be post-ischemic cerebral inflammation. This review presents the basis of pathophysiologic mechanisms of post-stroke inflammation and discusses possible targets and routes for therapeutic intervention.

Animals↗
PubMed2003

Atrial fibrillation: should we target platelets or the coagulation pathway?

Based on the established fact that anticoagulation with warfarin is superior to antiplatelet agents in the prevention of thromboembolic events in atrial fibrillation (AF), we propose that, in contrast to atherothrombotic disorders, the risk of developing a stroke or thromboembolic event in AF is more likely to be affected by the coagulation pathway than by platelet activity. Indeed, platelet-rich thrombi may be the predominant underlying pathophysiological process in coronary artery disease patients, thus representing an entirely different prothrombotic profile to the patients with AF, where clotting factor abnormalities (and thus fibrin-rich thrombi) are more likely. Thus, we would hypothesise that warfarin is probably more likely to be more beneficial than aspirin-clopidogrel combination therapy when used in this setting. Indeed, this hypothesis would need to be tested in large randomised clinical trials.

Aspirin↗