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Fulltext Autoimmune thyroid disease in a cohort of Malaysian SLE patients: frequency, clinical and immunological associations

Ong SG, Choy CH

Lupus, 2016 Jan;25(1):67-74.
PMID: 26113361 DOI: 10.1177/0961203315593164

Autoimmune thyroid disease (ATD) has been associated with other systemic autoimmune diseases. To date, there is limited data on thyroid disorders and autoimmune thyroid disease in Malaysia. The frequency of ATD among 189 systemic lupus erythematosus (SLE) patients was 6.3%, with 2.6% in the hyperthyroid group and 3.7% in the hypothyroid group. Hypothyroidism developed at a much younger mean age (24.3 years), suggesting that SLE might be a predisposing factor for the development of Hashimoto's thyroiditis. There was a higher rate of thyroid peroxidase antibody (TPO) positivity compared with anti-thyroglobulin antibody (Tg) in the hyperthyroid subgroup. This study also demonstrated a greater proportion of ATD patients who demonstrated high titres (≥ 1:6400) of TPO compared with high titres of Tg. Although there was an association between ATD and the presence of anti-Ro/SSA and/or anti-La/SSB antibodies, the absence of sicca symptoms and negative Schirmer's tests suggest a lack of association with secondary Sjogren's syndrome. A novel association between ATD and antiphospholipid syndrome (APS) was detected in our cohort. Hence we propose that patients affected by APS be routinely screened for ATD.
Renal sympathetic denervation in the treatment of resistant hypertension

Yap LB, Choy CN, Balachandran K

Med J Malaysia, 2021 Sep;76(5):777-780.
PMID: 34508396

Hypertension is a significant cardiovascular risk factor. Although the mainstay of treatment remains medication, there are a number of patients with resistant hypertension who have elevated blood pressure despite multiple medications. Failure to achieve adequately controlled blood pressures despite medications put these patients at risk of target organ damage and significant morbidity from hypertension. The renal denervation procedure involves the application of radiofrequency energy or ultrasound at the renal arteries to modulate afferent and efferent sympathetic renal activity. This treatment potentially can improve blood pressure control in patients who have resistant hypertension despite medication. This article presents two case reports of successful treatment of resistant hypertension using radiofrequency renal sympathetic denervation (RDN) at a private medical centre using the latest Spyral catheter. We also reviewed the latest RDN trials to give some insights into this procedure.
Intravascular ultrasound guided treatment of severe coronary artery calcification with Shockwave Intravascular Lithotripsy

Yap LB, Choy CN, Balachandran K

Med J Malaysia, 2022 Jan;77(1):116-118.
PMID: 35087010

Coronary artery calcification is a pathological deposition of calcium in the intimal and medial layer of the arterial wall. Shockwave intravascular lithotripsy (IVL) has evolved as a new modality to treat heavily calcified coronary arteries. IVL involves using a percutaneous device to produce acoustic pressure waves resulting in the delivery of sufficient energy to break up superficial and deep calcium deposits. We present a case where highly dense coronary calcium was successfully treated with intravascular ultrasound (IVUS) guided coronary angioplasty and IVL treatment. IVUS demonstrated heavy calcification at the proximal LAD with a 360° calcium arc. Post procedure, IVUS demonstrated multiple fractures of coronary calcium. Stent deployment was done successfully with good stent strut apposition. There was no procedure related complication. The case demonstrates an example where IVL is an important adjunctive tool in the cardiac catheterization laboratory for lesion preparation and optimal percutaneous coronary intervention.
Intravascular imaging-guided treatment of severe coronary artery calcification with orbital atherectomy: A prospective single-centre registry

Yap LB, Choy CN, Navin S, Koh KW, Jeyamalar R, Balachandran K

Med J Malaysia, 2023 Jan;78(1):7-13.
PMID: 36715184

INTRODUCTION: Coronary artery calcification can lead to suboptimal results when performing coronary angioplasty with conventional techniques. The presence of severe coronary artery calcium increases the complications of percutaneous coronary intervention as it may impede stent delivery and optimal stent expansion. The purpose of this study was to determine the procedural success and safety of orbital atherectomy (OA) in calcified lesions.
MATERIALS AND METHODS: This was a prospective single-centre study regarding the utility of OA in the treatment of calcified coronaries. Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was used in all cases to characterise the severity of calcium pre-procedure, guide vessel sizing and assess procedural success. The primary endpoint was procedural success, defined by successful stent implantation following OA treatment. The secondary endpoint was in-hospital and 30-day major adverse cardiovascular event (MACE).
RESULTS: Ten patients with severely calcified lesions were successfully treated with OA. The primary endpoint was achieved in all patients. All of the lesions were severely calcified with concentric calcium. None of the patients suffered in-hospital or 30-day MACE. The average minimal luminal diameter at baseline was 1.7 ± 0.3 mm and the post- PCI luminal diameter was 3.0 ± 0.3 mm, with a significant luminal gain of 1.3 ± 0.3 mm (p < 0.01). Slow flow during procedure occurred in 2 (20%) cases and dissection occurred in 1 (10%) case during procedure. These were successfully treated with stent delivery to achieve TIMI III flow. There were no cases of stent thrombosis or vessel perforation.
CONCLUSION: Our experience demonstrates the feasibility and safety of OA in the management of calcified coronary stenosis. Intravascular imaging is an important adjunct to the use of OA to assess the severity of calcified coronary lesions, success of OA treatment and to aid sizing of the vessel for stent implantation. OA is an effective treatment approach to disrupt coronary calcification, facilitating stent implantation with optimal results. It is a safe procedure with good success rate and low rate of complications.
Immunohistochemical expression of NANOG in urothelial carcinoma of the bladder

Md Akhir MKA, Hussin H, Veerakumarasivam A, Choy CS, Abdullah MA, Abd Ghani F

Malays J Pathol, 2017 Dec;39(3):227-234.
PMID: 29279584 MyJurnal

Urothelial carcinoma is a common malignant neoplasm that has a poor prognosis and a high frequency of recurrence and metastasis. Constant disease surveillance with periodic and long term cystoscopy examination is necessary for management of the disease. However, the monitoring and therapy regimen is expensive, incurring a massive burden to patients and the government. Therefore, the development of specific biomarkers for urothelial carcinoma at an early stage and recurrence detection becomes a priority. Homeobox genes are a family of genes that are involved in tumourigenesis. They might be potential prognostic markers for urothelial carcinoma. The study investigated the expression pattern of NANOG which is one of a homeobox gene in different stages and grades of urothelial carcinoma. NANOG expressions were also correlated with patient demographic factors and clinicopathological parameters. The expression of NANOG in 100 formalin-fixed paraffin-embedded urothelial carcinoma tissues was determined by immunohistochemistry. Immunohistochemistry showed positive expression of NANOG in all specimens with detection in the cytoplasm, nuclei and the nuclear membrane of the cancer cells. The immunohistochemical expression of NANOG increased across stages and grades of the tumour. The expression of NANOG was not significantly associated with demographic factors; gender (p = 0.376), race (p = 0.718) and age (p = 0.058) as well as with most of the clinicopathological parameters; pathological stage (p = 0.144), grade (p = 0.625), lymph node involvement (p = 0.174) and distant metastasis (p = 0.228). However, NANOG expression showed significant correlation with tumour invasion (p = 0.019). We concluded that NANOG might be a potential biomarker for early diagnosis of urothelial carcinoma of the bladder.
Exploring Intestinal Surface Receptors in Oral Nanoinsulin Delivery

Choy C, Lim LY, Chan LW, Cui Z, Mao S, Wong TW

Pharmacol Rev, 2022 Oct;74(4):962-983.
PMID: 36779351 DOI: 10.1124/pharmrev.122.000631

Subcutaneous and inhaled insulins are associated with needle phobia, lipohypertrophy, lipodystrophy, and cough in diabetes treatment. Oral nanoinsulin has been developed, reaping the physiologic benefits of peroral administration. This review profiles intestinal receptors exploitable in targeted delivery of oral nanoinsulin. Intestinal receptor targeting improves oral insulin bioavailability and sustains blood glucose-lowering response. Nonetheless, these studies are conducted in small animal models with no optimization of insulin dose, targeting ligand type and content, and physicochemical and molecular biologic characteristics of nanoparticles against the in vivo/clinical diabetes responses as a function of the intestinal receptor population characteristics with diabetes progression. The interactive effects between nanoinsulin and antidiabetic drugs on intestinal receptors, including their up-/downregulation, are uncertain. Sweet taste receptors upregulate SGLT-1, and both have an undefined role as new intestinal targets of nanoinsulin. Receptor targeting of oral nanoinsulin represents a viable approach that is relatively green, requiring an in-depth development of the relationship between receptors and their pathophysiological profiles with physicochemical attributes of the oral nanoinsulin. SIGNIFICANCE STATEMENT: Intestinal receptor targeting of oral nanoinsulin improves its bioavailability with sustained blood glucose-lowering response. Exploring new intestinal receptor and tailoring the design of oral nanoinsulin to the pathophysiological state of diabetic patients is imperative to raise the insulin performance to a comparable level as the injection products.
Left main stem stenosis angioplasty with intravascular ultrasound optimisation criteria guidance using a new generation everolimus drug-eluting stent

Yap LB, Choy CN, Koh KW, Kannan P, Jeyamalar R, Navin S, et al.

Med J Malaysia, 2023 Mar;78(2):139-144.
PMID: 36988521

INTRODUCTION: Intravascular ultrasound (IVUS) is recommended in the use of left main stem (LMS) percutaneous coronary intervention (PCI). Since the LMS diameter is usually larger than other coronary arteries, a new generation everolimus drug-eluting stent (DES), Synergy Megatron DES (Boston Scientific) has better axial and radial strength allowing more post implant overexpansion and consequently better suited for LMS lesions. We performed a study to evaluate the clinical outcomes of PCI using 1) an improved IVUS protocol with optimisation targets and 2) the use of Megatron stents.
MATERIALS AND METHODS: This was a study involving LMS PCI coronary lesions using the Synergy Megatron DES. An IVUS protocol using predefined optimisation targets to evaluate for stent malapposition, longitudinal stent deformation, optimal stent expansion >90% of reference lumen and appropriate distal landing zone was used in all cases. The primary end-point was procedural success, defined by successful stent implantation with <30% residual stenosis. The secondary end-point was in-hospital and 30-day major adverse cardiovascular event (MACE).
RESULTS: Eight patients with significant LMS stenosis were successfully treated with the Megatron stent. The primary end-point was achieved in all patients. There were no cases of stent malapposition or longitudinal stent deformation, one case did not have optimal LMS stent expansion and one case did not have an appropriate distal landing zone. IVUS optimisation criteria were met in 6 (75%) cases. There were no complications of coronary dissection, slow or no reflow, stent thrombosis or vessel perforation. None of the patients suffered in-hospital or 30-day MACE. The average LMS MLD at baseline was 2.1 ± 0.1mm and the post-PCI LMS MLD was 4.0 ± 0.5mm, with a significant acute luminal gain of 1.9 ± 0.7mm (p<0.01). A post-PCI MSA of 17 ± 3.9 mm2 was numerically superior compared to those documented in other LMS PCI trials.
CONCLUSION: This study demonstrates low rates of shortterm major adverse cardiovascular events among patients with LMS PCI using the Megatron stents. It highlights the usefulness of IVUS-guided optimisation in LMS PCI. With the use of intravascular imaging, the new generation stent technology can improve the treatment of large proximal vessels and PCI of LMS lesions.