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  1. Jeyamalar R, Pathmanathan R, Wong D, Kannan P
    Ann Acad Med Singap, 1992 Nov;21(6):838-40.
    PMID: 1295429
    Amiodarone, a commonly used antiarrhythmic agent, has numerous adverse effects. The purpose of this case report is to highlight its hepatotoxicity, an unusual complication of long term amiodarone therapy. Our patient is a 76-year-old man with underlying ischaemic heart disease and recurrent ventricular tachycardia. Eleven months after commencing amiodarone, he developed asymptomatic raised aminotransferases which resolved following drug withdrawal. Amiodarone was then reintroduced and four years later, the patient developed hepatomegaly, worsening liver biochemistry and histopathological changes consistent with early cirrhosis. His symptoms improved following discontinuation of amiodarone. However, hepatomegaly and a low serum albumin still persist four years later.
  2. Wong D, Ramachandra SS, Singh AK
    Contemp Clin Dent, 2015 9 1;6(3):418-20.
    PMID: 26321847 DOI: 10.4103/0976-237X.161908
    Williams syndrome is a multisystemic rare genetic disorder caused by deletion of 26-28 genes in the long arm of chromosome 7. It is characterized by developmental and physical abnormalities including congenital cardiovascular abnormalities, mental retardation, neurological features, growth deficiency, genitourinary manifestations, gastrointestinal problems, musculoskeletal problems, unique behavioral characteristics, and dental problems. Dental abnormalities include malocclusion, hypodontia, malformed teeth, taurodontism, pulp stones, increased space between teeth, enamel hypoplasia, and high prevalence of dental caries. Authors report a 17-year-old female patient with underlying Williams syndrome. Oral features and problems seen in the patient are listed. Malocclusion and screwdriver shaped teeth were noticed. Generalized widening of the periodontal ligament space with vital teeth was seen. This finding has not been reported in cases of Williams syndrome earlier. Precautions taken during dental treatment in patients with Williams syndrome are also discussed.
  3. Soga T, Wong DW, Putteeraj M, Song KP, Parhar IS
    Neuroscience, 2012 Dec 6;225:172-84.
    PMID: 22960312 DOI: 10.1016/j.neuroscience.2012.08.061
    Postnatal treatment with selective serotonin reuptake inhibitors (SSRIs) has been found to affect brain development and the regulation of reproduction in rodent models. The normal masculinization process in the brain requires a transient decrease in serotonin (5-HT) levels in the brain during the second postnatal week. Strict regulation of androgen receptor (AR) and gonadotropin-releasing hormone (GnRH) expression is important to control male reproductive activity. Therefore, this study was designed to examine the effects of a potent SSRI (citalopram) on male sexual behavior and expression levels of AR and GnRH in adult male mice receiving either vehicle or citalopram (10mg/kg) daily during postnatal days 8-21. The citalopram-treated male mice showed altered sexual behavior, specifically a significant reduction in the number of intromissions preceding ejaculation compared with the vehicle-treated mice. The citalopram-treated male mice displayed elevated anxiety-like behavior in an open field test and lower locomotor activity in their home cage during the subjective night. Although there was no change in GnRH and AR mRNA levels in the preoptic area (POA), quantified by real-time polymerase chain reaction, immunostained AR cell numbers in the medial POA were decreased in the citalopram-treated male mice. These results suggest that the early-life inhibition of 5-HT transporters alters the regulation of AR expression in the medial POA, likely causing decreased sexual behavior and altered home cage activity in the subjective night.
  4. Soga T, Dalpatadu SL, Wong DW, Parhar IS
    Neuroscience, 2012 Aug 30;218:56-64.
    PMID: 22626647 DOI: 10.1016/j.neuroscience.2012.05.023
    Synthetic glucocorticoid (dexamethasone; DEX) treatment during the neonatal stage is known to affect reproductive activity. However, it is still unknown whether neonatal stress activates gonadotropin-inhibitory hormone (GnIH) synthesizing cells in the dorsomedial hypothalamus (DMH), which could have pronounced suppressive action on gonadotropin-releasing hormone (GnRH) neurons, leading to delayed pubertal onset. This study was designed to determine the effect of neonatal DEX (1.0mg/kg) exposure on reproductive maturation. Therefore, GnRH, GnIH and GnIH receptors, G-protein coupled receptors (GPR) 147 and GPR74 mRNA levels were measured using quantitative real-time PCR in female mice at postnatal (P) days 21, 30 and in estrus stage mice, aged between P45-50. DEX-treated females of P45-50 had delayed vaginal opening, and irregular estrus cycles and lower GnRH expression in the preoptic area (POA) when compared with age-matched controls. The expression levels of GPR147 and GPR74 mRNA in the POA increased significantly in DEX-treated female mice of P21 and P45-50 compared to controls. In addition, GPR147 and GPR74 mRNA expression was observed in laser captured single GnRH neurons in the POA. Although there was no difference in GnIH mRNA expression in the DMH, immunostained GnIH cell numbers in the DMH increased in DEX-treated females of P45-50 compared to controls. Taken together, the results show that the delayed pubertal onset could be due to the inhibition of GnRH gene expression after neonatal DEX treatment, which may be accounted for in part by the inhibitory signals from the up-regulated GnIH-GnIH receptor pathway to the POA.
  5. Wong DKC, Gendeh HS, Thong HK, Lum SG, Gendeh BS, Saim A, et al.
    Med J Malaysia, 2020 09;75(5):574-581.
    PMID: 32918429
    INTRODUCTION: Multiple anecdotal reports suggest that smell and taste loss were early subclinical symptoms of COVID-19 patients. The objective of this review was to identify the incidence of smell and taste dysfunction in COVID-19, determine the onset of their symptoms and the risk factors of anosmia, hyposmia, ageusia or dysgeusia for COVID-19 infection.

    METHODS: We searched the PubMed and Google Scholar on 15th May 2020, with search terms including SARS-COV-2, coronavirus, COVID-19, hyposmia, anosmia, ageusia and dysgeusia. The articles included were cross sectional studies, observational studies and retrospective or prospective audits, letters to editor and short communications that included a study of a cohort of patients. Case reports, case-series and interventional studies were excluded.

    DISCUSSION: A total of 16 studies were selected. Incidence of smell and taste dysfunction was higher in Europe (34 to 86%), North America (19 to 71%) and the Middle East (36 to 98%) when compared to the Asian cohorts (11 to 15%) in COVID-19 positive patients. Incidence of smell and taste dysfunction in COVID-19 negative patients was low in comparison (12 to 27%). Total incidence of smell and taste dysfunction from COVID-19 positive and negative patients from seven studies was 20% and 10% respectively. Symptoms may appear just before, concomitantly, or immediately after the onset of the usual symptoms. Occurs predominantly in females. When occurring immediately after the onset of the usual symptoms, the median time of onset was 3.3 to 4.4 days. Symptoms persist for a period of seven to 14 days. Patients with smell and taste dysfunction were reported to have a six to ten-fold odds of having COVID-19.

    CONCLUSION: Smell and taste dysfunction has a high incidence in Europe, North America, and the Middle East. The incidence was lower in the Asia region. It is a strong risk factor for COVID-19. It may be the only symptom and should be added to the list of symptoms when screening for COVID- 19.

  6. Wong DKC, Muhamad NS, Sobri SS, Amin WAM, Yusof Z
    Med J Malaysia, 2019 04;74(2):85-86.
    PMID: 31079134
    Metastasising pleomorphic adenoma is rare and may occur years after surgical excision of a pleomorphic adenoma (PA). We present a 61-year-old woman with a right infratemporal PA with metastases to the cervical lymph nodes after 30 years following a total parotidectomy. She was treated successfully with a resection of the tumour with combined neck and mandibulotomy approach along with postoperative radiotherapy given subsequently.
  7. Ooi MH, Wong SC, Podin Y, Akin W, del Sel S, Mohan A, et al.
    Clin Infect Dis, 2007 Mar 01;44(5):646-56.
    PMID: 17278054
    BACKGROUND: Human enterovirus (HEV)-71 causes large outbreaks of hand-foot-and-mouth disease with central nervous system (CNS) complications, but the role of HEV-71 genogroups or dual infection with other viruses in causing severe disease is unclear.

    METHODS: We prospectively studied children with suspected HEV-71 (i.e., hand-foot-and-mouth disease, CNS disease, or both) over 3.5 years, using detailed virological investigation and genogroup analysis of all isolates.

    RESULTS: Seven hundred seventy-three children were recruited, 277 of whom were infected with HEV-71, including 28 who were coinfected with other viruses. Risk factors for CNS disease in HEV-71 included young age, fever, vomiting, mouth ulcers, breathlessness, cold limbs, and poor urine output. Genogroup analysis for the HEV-71-infected patients revealed that 168 were infected with genogroup B4, 68 with C1, and 41 with a newly emerged genogroup, B5. Children with HEV-71 genogroup B4 were less likely to have CNS complications than those with other genogroups (26 [15%] of 168 vs. 30 [28%] of 109; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.91; P=.0223) and less likely to be part of a family cluster (12 [7%] of 168 vs. 29 [27%] of 109; OR, 0.21; 95% CI, 0.10-0.46; P

  8. Mahmood A, Needham K, Shakur-Still H, Harris T, Jamaluddin SF, Davies D, et al.
    Emerg Med J, 2021 Apr;38(4):270-278.
    PMID: 33262252 DOI: 10.1136/emermed-2020-210424
    BACKGROUND: Early tranexamic acid (TXA) treatment reduces head injury deaths after traumatic brain injury (TBI). We used brain scans that were acquired as part of the routine clinical practice during the CRASH-3 trial (before unblinding) to examine the mechanism of action of TXA in TBI. Specifically, we explored the potential effects of TXA on intracranial haemorrhage and infarction.

    METHODS: This is a prospective substudy nested within the CRASH-3 trial, a randomised placebo-controlled trial of TXA (loading dose 1 g over 10 min, then 1 g infusion over 8 hours) in patients with isolated head injury. CRASH-3 trial patients were recruited between July 2012 and January 2019. Participants in the current substudy were a subset of trial patients enrolled at 10 hospitals in the UK and 4 in Malaysia, who had at least one CT head scan performed as part of the routine clinical practice within 28 days of randomisation. The primary outcome was the volume of intraparenchymal haemorrhage (ie, contusion) measured on a CT scan done after randomisation. Secondary outcomes were progressive intracranial haemorrhage (post-randomisation CT shows >25% of volume seen on pre-randomisation CT), new intracranial haemorrhage (any haemorrhage seen on post-randomisation CT but not on pre-randomisation CT), cerebral infarction (any infarction seen on any type of brain scan done post-randomisation, excluding infarction seen pre-randomisation) and intracranial haemorrhage volume (intraparenchymal + intraventricular + subdural + epidural) in those who underwent neurosurgical haemorrhage evacuation. We planned to conduct sensitivity analyses excluding patients who were severely injured at baseline. Dichotomous outcomes were analysed using relative risks (RR) or hazard ratios (HR), and continuous outcomes using a linear mixed model.

    RESULTS: 1767 patients were included in this substudy. One-third of the patients had a baseline GCS (Glasgow Coma Score) of 3 (n=579) and 24% had unilateral or bilateral unreactive pupils. 46% of patients were scanned pre-randomisation and post-randomisation (n=812/1767), 19% were scanned only pre-randomisation (n=341/1767) and 35% were scanned only post-randomisation (n=614/1767). In all patients, there was no evidence that TXA prevents intraparenchymal haemorrhage expansion (estimate=1.09, 95% CI 0.81 to 1.45) or intracranial haemorrhage expansion in patients who underwent neurosurgical haemorrhage evacuation (n=363) (estimate=0.79, 95% CI 0.57 to 1.11). In patients scanned pre-randomisation and post-randomisation (n=812), there was no evidence that TXA reduces progressive haemorrhage (adjusted RR=0.91, 95% CI 0.74 to 1.13) and new haemorrhage (adjusted RR=0.85, 95% CI 0.72 to 1.01). When patients with unreactive pupils at baseline were excluded, there was evidence that TXA prevents new haemorrhage (adjusted RR=0.80, 95% CI 0.66 to 0.98). In patients scanned post-randomisation (n=1431), there was no evidence of an increase in infarction with TXA (adjusted HR=1.28, 95% CI 0.93 to 1.76). A larger proportion of patients without (vs with) a post-randomisation scan died from head injury (38% vs 19%: RR=1.97, 95% CI 1.66 to 2.34, p<0.0001).

    CONCLUSION: TXA may prevent new haemorrhage in patients with reactive pupils at baseline. This is consistent with the results of the CRASH-3 trial which found that TXA reduced head injury death in patients with at least one reactive pupil at baseline. However, the large number of patients without post-randomisation scans and the possibility that the availability of scan data depends on whether a patient received TXA, challenges the validity of inferences made using routinely collected scan data. This study highlights the limitations of using routinely collected scan data to examine the effects of TBI treatments.

    TRIAL REGISTRATION NUMBER: ISRCTN15088122.

  9. Mohan A, Podin Y, Tai N, Chieng CH, Rigas V, Machunter B, et al.
    PLoS Negl Trop Dis, 2017 Jun;11(6):e0005650.
    PMID: 28599008 DOI: 10.1371/journal.pntd.0005650
    BACKGROUND: Melioidosis is a serious, and potentially fatal community-acquired infection endemic to northern Australia and Southeast Asia, including Sarawak, Malaysia. The disease, caused by the usually intrinsically aminoglycoside-resistant Burkholderia pseudomallei, most commonly affects adults with predisposing risk factors. There are limited data on pediatric melioidosis in Sarawak.

    METHODS: A part prospective, part retrospective study of children aged <15 years with culture-confirmed melioidosis was conducted in the 3 major public hospitals in Central Sarawak between 2009 and 2014. We examined epidemiological, clinical and microbiological characteristics.

    FINDINGS: Forty-two patients were recruited during the 6-year study period. The overall annual incidence was estimated to be 4.1 per 100,000 children <15 years, with marked variation between districts. No children had pre-existing medical conditions. Twenty-three (55%) had disseminated disease, 10 (43%) of whom died. The commonest site of infection was the lungs, which occurred in 21 (50%) children. Other important sites of infection included lymph nodes, spleen, joints and lacrimal glands. Seven (17%) children had bacteremia with no overt focus of infection. Delays in diagnosis and in melioidosis-appropriate antibiotic treatment were observed in nearly 90% of children. Of the clinical isolates tested, 35/36 (97%) were susceptible to gentamicin. Of these, all 11 isolates that were genotyped were of a single multi-locus sequence type, ST881, and possessed the putative B. pseudomallei virulence determinants bimABp, fhaB3, and the YLF gene cluster.

    CONCLUSIONS: Central Sarawak has a very high incidence of pediatric melioidosis, caused predominantly by gentamicin-susceptible B. pseudomallei strains. Children frequently presented with disseminated disease and had an alarmingly high death rate, despite the absence of any apparent predisposing risk factor.

  10. Srinivasan S, Yeri A, Cheah PS, Chung A, Danielson K, De Hoff P, et al.
    Cell, 2019 04 04;177(2):446-462.e16.
    PMID: 30951671 DOI: 10.1016/j.cell.2019.03.024
    Poor reproducibility within and across studies arising from lack of knowledge regarding the performance of extracellular RNA (exRNA) isolation methods has hindered progress in the exRNA field. A systematic comparison of 10 exRNA isolation methods across 5 biofluids revealed marked differences in the complexity and reproducibility of the resulting small RNA-seq profiles. The relative efficiency with which each method accessed different exRNA carrier subclasses was determined by estimating the proportions of extracellular vesicle (EV)-, ribonucleoprotein (RNP)-, and high-density lipoprotein (HDL)-specific miRNA signatures in each profile. An interactive web-based application (miRDaR) was developed to help investigators select the optimal exRNA isolation method for their studies. miRDar provides comparative statistics for all expressed miRNAs or a selected subset of miRNAs in the desired biofluid for each exRNA isolation method and returns a ranked list of exRNA isolation methods prioritized by complexity, expression level, and reproducibility. These results will improve reproducibility and stimulate further progress in exRNA biomarker development.
  11. Wilkinson JL, Boxall ABA, Kolpin DW, Leung KMY, Lai RWS, Galbán-Malagón C, et al.
    Proc Natl Acad Sci U S A, 2022 Feb 22;119(8).
    PMID: 35165193 DOI: 10.1073/pnas.2113947119
    Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.
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