The Role of Vitamin D Receptor Polymorphisms in Predicting the Response to Therapy for Nonmuscle Invasive Bladder Carcinoma.

PURPOSE: Clinical and pathological predictors of bladder carcinoma recurrence and progression are relatively well defined. However, there is a paucity of genetic data specifically on the association of single nucleotide polymorphisms in specific genes for predicting recurrence and progression following immunotherapy. The VDR gene was found to regulate the immunomodulatory effects of vitamin D and it enhances the innate immunity system. We evaluated 3 VDR single nucleotide polymorphisms and their predictive role on the response to immunotherapy. MATERIALS AND METHODS: Patients with bladder cancer at intermediate-high risk who underwent post-transurethral resection intravesical bacillus Calmette-Guérin in Singapore and Hong Kong from 1995 to 2014 were recruited for analysis. We evaluated 3 VDR single nucleotide polymorphisms using polymerase chain reaction. Kaplan-Meier survival curves and relationships with outcomes were analyzed by multivariable Cox regression. RESULTS: A total of 338 predominantly Chinese patients were included in study. Individuals carrying the VDR genotype Bsm A/G were significantly associated with lower time to recurrence after bacillus Calmette-Guérin therapy (p <0.001). On multivariable analysis the HR of recurrence in patients with the Bsm A allele was 3.95 times that in patients without the allele (p = 0.037). Patients with the VDR GATC subhaplotype were 3.05 times more likely than patients with other subhaplotypes to experience recurrences (p = 0.003). Study limitations include the small sample size and the lack of information on previous bacillus Calmette-Guérin vaccine exposure and on vitamin D levels. CONCLUSIONS: Our findings in this study suggest that various VDR single nucleotide polymorphisms are associated with recurrences after bacillus Calmette-Guérin immunotherapy. Further functional studies should be performed to elucidate the significance of the VDR gene in the management of bladder cancer and the potential therapy implications.

Late presentation of ALCAPA syndrome in an elderly Asian lady.

Coronary artery anomalies are often discovered incidentally during cardiac catheterization or computed tomography coronary angiography and may involve the affected coronary artery origin and its course. Coronary artery anomalies are associated with congenital heart disease. The affected coronary arteries may have an unusual high take off origin, origin from contralateral or non-coronary sinus, origin from the pulmonary artery, single coronary system or coronary artery fistula.

Towards Mainstream Adoption of Tenecteplase for the Treatment of Acute Myocardial Infarction.

No abstract available.

Cannulated versus non-cannulated cancellous screw fixation for femoral neck fractures: a synthetic bone biomechanical study.

PURPOSE: To compare the compressive strength of cannulated versus non-cannulated cancellous screws for undisplaced femoral neck fractures in synthetic bones. METHODS: 18 synthetic proximal femurs simulating an AO B1 valgus impacted femoral neck fracture in osteoporotic bone were used. The fracture angles were between 55º and 63º (Pauwels grade 2). Fixation was made using 6.5-mm non-cannulated screws (n=6), 6.5-mm cannulated screws (n=6), or 7.3-mm cannulated screws (n=6). A custom-built jig was designed to guide the insertion of the screws in an identical triangular configuration. Screws were tightened by a single operator using a torque-measuring screwdriver. The femoral head was subjected to progressive axial loading at 5 mm/min. The load to failure and displacement were recorded. RESULTS: The 3 groups did not differ significantly except that the load to failure was higher in the construct with 6.5-mm non-cannulated screws than that with 6.5-mm cannulated screws (1222 N vs 1008 N, p=0.003). CONCLUSION: The compressive strength of a synthetic bone hip fracture model fixed with non-cannulated screws was higher than that of cannulated screws of the same diameter.

Carotid intima media thickness and high sensitivity C-reactive protein as markers of cardiovascular risk in a malaysian population.

INTRODUCTION: Carotid intima media thickness (CIMT) being a cost effective and easily performed technique is useful in the detection of subclinical atherosclerosis and has been shown to be a prognosticator of cardiovascular events. The primary objective of this study was to obtain the distribution of CIMT measurements, highly sensitive C reactive protein (hs-CRP) and assessing health awareness and attitudes of the Malaysian population at cardiovascular disease (CVD) risk and not receiving lipid lowering agents. Secondarily the study sought to assess the significance of the relationship between these measurements against various patient characteristics. METHODS: Measurements of CIMT are obtained by ultrasonography of 12 sites within the common carotid artery was recorded for 123 subjects from a single centre tertiary hospital of Malaysia who had two or more CVD risk factors but were not receiving lipid lowering therapy. CVD risk factors and lipid and glucose profiles were analyzed with respect to distribution of CIMT and high-sensitivity Creactive protein (hs-CRP) values. RESULTS: The mean-max CIMT was 0.916±0.129mm (minimum 0.630mm, maximum 1.28mm) and the mean-mean CIMT was 0.743±0.110mm (minimum 0.482mm, maximum 1.050mm) and mean hs-CRP was 0.191mg/dL (minimum 0.030mg/dL, maximum 5.440mg/dL). Multivariate analyses confirmed a significant association between increasing CIMT and increasing age, total and low density lipoprotein cholesterol while log-transformed hs-CRP levels showed significant association with increasing body mass index, waist circumference, high blood glucose and triglyceride levels. Our patients had good health awareness on CVD. CONCLUSION: Newly defined CIMT measurements and hs-CRP levels may be useful adjunctive tools to screen for atherosclerosis in the Malaysian population. It may help in refining risk stratification on top of traditional clinical assessment.

Arteria Lusoria and Persistent Left Superior Vena Cava: Vessel Aberrancy is A Bane for Cardiologist Too.

No abstract available.

The entrapped and unravelled coronary wire.

No abstract available.

Total intravenous anaesthesia approach to overcome the phenomenon of left bundle branch block induced by general anaesthesia.

No abstract available.

Exotic food anaphylaxis and the broken heart: sago worm and takotsubo cardiomyopathy.

There is increasing consumption of exotic food in Malaysia. Animals such as insects, worms and wild life animals also form part of the staple food of the local population. This practice may lead to more incidence of food allergy and anaphylaxis. We report a non-indigenous man who developed food anaphylaxis after consuming fried sago worms and consequently Takotsubo cardiomyopathy. We postulate that certain food allergy and anaphylaxis could be another causative trigger for Takotsubo cardiomyopathy.

Infective endocarditis and the pacemaker: cardiac implantable electronic device infection.

We are seeing more implantation of cardiac device such as pacemakers and defibrillators and also cardiac implantable electronic device infection. The infection may affect just the pocket site or progress to deeper infection and bacteraemia. Inadequately treated infection may lead to right sided endocarditis, cardiotomy for pacemaker explantation and increased cost and length of stay in the hospital. We report a Staphylococcal infection of a pacemaker system, its successful medical and surgical management.

Blockade of Lyn kinase upregulates both canonical and non-canonical TLR-3 pathways in THP-1 monocytes exposed to human cytomegalovirus.

Regulation of monocyte response to human cytomegalovirus (HCMV) occurs via activation of receptors that elicit innate antiviral effects and later T-cell responses. Our previous data (Yew et al.., 2010) demonstrated that human monocyte scavenger receptor A type 1 (SR-A1) are required for sensing of HCMV by endosomal toll-like receptors (TLRs)-3 and -9, which in turn induce critical pro-inflammatory cytokines. However, it remains unclear which subcellular molecules associated with SR-A1 lead to downstream activation of TLR-3 and/or TLR-9 signaling pathways. Herein we report that Lyn kinase, associated physically and functionally with SR-A for low density lipoprotein (LDL) recognition, acts as a key SR-A1-induced kinase that plays a critical role in TLR-3/9 signal transduction upon HCMV exposure to THP-1 monocytes. We found that disruption of the SR-A1 signal transduction through molecular inhibition by Lyn kinase oligonucleotides not only blocks the activation of downstream TLR-9 pathway but also alters the downstream TLR-3 pathway. In particular, Lyn kinase oligonucleotides resulted in decreased expression of TLR-9-induced tumor necrosis factor alpha (TNF-α) but strongly upregulated canonical TLR-3-induced interferon beta (IFN-ß) and non-canonical TLR-3-induced NF-κB-dependent p35 (35kDa) subunit of interleukin 12 (IL-12p35) gene transcription. Thus, the observed shift away from TNF-α to robust IFN-ß and IL-12p35 induction may offer opportunities for therapeutic interventions.

The bug and the big heart --melioidotic pericardial effusion.

Melioidosis is an infection caused by Gram negative bacterium Burkholderia pseudomallei leading to abscesses in lungs, liver, spleen, musculoskeletal system, prostate and sepsis. We present a rare case of purulent pericardial effusion caused by melioidosis with concomitant pneumonia and splenic abscesses. The patient underwent pericardiocentesis and successfully recovered from cardiogenic and septic shock.

Subclinical coronary artery disease in Asian rheumatoid arthritis patients who were in remission: a pilot study.

INTRODUCTION: Rheumatoid arthritis (RA) patients who have active disease with longer disease duration have been reported to have increased risk of cardiovascular events compared to the normal population. OBJECTIVE: The primary aim of our study is to ascertain the prevalence of significant asymptomatic coronary artery disease (CAD) in Asian RA patients who are in remission using multi-detector computed tomography (MDCT). The secondary aims of our study are the usage of pulse wave velocity and the biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-senstivity C-reactive protein (hs-CRP) to detect subclinical atherosclerosis in RA patients. METHODS: We performed a comparative cross-sectional study of 47 RA patients who were in remission with a control group of non-RA patients with a history of atypical chest pain in Sarawak General Hospital from November 2008 to February 2009. All patients underwent 64-slice MDCT, assessment of arterial stiffness using the SphygmoCor test and blood analysis for NT-proBNP and hsCRP. RESULTS: There were 94 patients in our study with a mean age of 50 +/- 8.8 years. The RA and control patients in each group were matched in terms of traditional CV risk factors. Our RA patients had a median disease duration of 3 years (IQR 5.5). MDCT showed evidence of CAD in nine (19.1%) RA patients and three (6.4%) control patients (P = 0.06). There was no significant association between pulse wave velocity (PWV) and presence of CAD in our RA group. There was no significant correlation between PWV with levels of proBNP or hsCRP in our RA patients. CONCLUSIONS: In our current pilot study with the limitation of small sample size, RA was not associated with an increased risk of CAD in our RA patients who were in remission. Larger studies of CAD in Asian RA patients are needed to confirm our current finding.

New developments in transnasal endoscopic surgery for malignancies of the sinonasal tract and adjacent skull base.

PURPOSE OF REVIEW: Technological advances and technical innovations have spearheaded an expansion in the indications for endoscopic sinonasal surgery, which now extend to the resection of sinonasal and skull base malignancies. This review examines recent advances that have contributed to make this technique feasible and reviews the basis of adopting an endonasal approach. RECENT FINDINGS: Oncologic goals developed for traditional skull base surgery can be safely applied to endoscopic skull base surgery. This has been made possible with the advent of better understanding of skull base anatomy from the endonasal perspective, as well as the development of better instrumentation, better hemostatic materials and more reliable reconstructive techniques. Recent publications have reported similar short-term outcomes for endoscopic skull base resection as compared with traditional approaches with lower complication rates. SUMMARY: Transnasal endoscopic surgery is an important part of the surgical armamentarium for the treatment of sinonasal and skull base malignancies. New technologies will further expand the limits of what can be achieved endoscopically. Collaborative multiinstitutional studies with long-term follow-up are crucial in defining the role of endoscopic resection in the treatment of skull base malignancies.