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The natural progression and outcomes of adrenal incidentaloma: a systematic review and meta-analysis

Loh HH, Yee A, Loh HS, Sukor N, Kamaruddin NA

Minerva Endocrinol., 2015 Dec 23.
PMID: 26698544 DOI: 10.23736/S0391-1977.16.02394-4

INTRODUCTION: Long-term outcome of patients with adrenal incidentaloma (AI) is unknown. The aim of this study was to systematically summarize the follow-up and outcome of clinically silent AI who do not undergo surgery.
EVIDENCE ACQUISITION: All major databases and medical literature in English-language, published from 1998 to May 2015, were systematically searched for publications on AI. Primary endpoint was hormonal hyper function; secondary endpoints were time from diagnosis to study endpoint and the outcome of adrenalectomy. Meta-analysis was performed using both qualitative and quantitative approach.
EVIDENCE SYNTHESIS: A total of 11 publications were included. Total sample size was 1298 patients. Mean follow-up duration was 44.2 months. There were 82 patients confirmed to have subclinical Cushing's syndrome at diagnosis, with 1.79% new cases at the end of follow up (95% CI, 0.002 to 0.045). Incidence of Cushing's syndrome was 0.7% (95% CI, 0.001 to 0.013) and pheochromocytoma 0.4% (95% CI, 0.001 to 0.008). The mean tumor size was 2.52cm, with mean increment of 0.03cm to 2.9cm at the end of follow up. About 3% of patients ended up with surgery (95% CI, 0.01 to 0.05) but none were due to primary adrenal malignancy. Time of greatest risk of developing Cushing's syndrome and pheochromocytoma was between months 36 and 42 (hazard rate 14%), and between months 48 and 54 (hazard rate 7%) respectively.
CONCLUSIONS: Malignant change in non-functioning AI is rare. The risk of developing overt disease over the follow-up period is low. A less stringent imaging and functional work-up interval can be considered.
Fulltext Reappraisal of bovril as a source of arginine in the arginine stimulation test for growth hormone deficiency

Loh HH, Norlela S, Nor Azmi K

Med J Malaysia, 2015 Jun;70(3):208-9.
PMID: 26248787 MyJurnal

The purpose of this case study is to report the use of oral Bovril (a food supplement which contains arginine) as an alternative test for growth hormone stimulation test. We performed oral Bovril test in 3 patients -- one with suspected growth hormone deficiency in whom insulin tolerance test could not be performed (subject A), one sex-matched control (subject B), and one with confirmed growth hormone deficiency (subject C). 14g/m(2) of oral Bovril was mixed with 150ml of warm water and was given to all three subjects. Blood for growth hormone was taken at baseline, and every 30 minutes till 150 minutes after ingestion of oral Bovril. The ingestion of oral Bovril showed a positive response in subjects A and B, with highest growth hormone levels of 28.4mIU/L and 42.0mIU/L respectively at 150 minutes. Subject C had suppressed growth hormone throughout the test. Oral Bovril is readily available and is a safe alternative for standard growth hormone stimulation test.
Fulltext No evidence for association between DRD3 and COMT with schizophrenia in a Malay population

Tee SF, Tang PY, Loh HC

Genet. Mol. Res., 2011;10(3):1850-5.
PMID: 21948748 DOI: 10.4238/vol10-3gmr1237

Molecular components of the dopamine D3 receptor (DRD3) may play an important role in the pathophysiology of schizophrenia. Previous studies have demonstrated an association between DRD3 Ser9Gly and cathechol-o-methyltransferase (COMT, SNP = rs165656) polymorphisms and schizophrenia but the results were inconclusive. We investigated this apparent association between Ser9Gly (A/G) polymorphism and an intronic SNP (dbSNP or rs165656) in 261 Malay patients diagnosed with schizophrenia and 216 controls, using PCR-RFLP. The genotype distribution of the polymorphism DRD3 Ser9Gly was in Hardy-Weinberg equilibrium (HWE) for patients (P = 0.1251) and out of HWE for controls (P = 0.0137). However, both healthy controls and schizophrenia patients were out of HWE for the polymorphism COMT rs165656. Based on allele and genotype frequencies in both groups, we found no significant association of DRD3 Ser9Gly polymorphisms and COMT (rs165656) with schizophrenia in Malays. Further studies should examine the association between other dopamine-related genes and the behavioral phenotypes of schizophrenia.
Development of a quantitative real-time RT-PCR for kinetic analysis of immediate-early transcripts of rat cytomegalovirus

Loh HS, Mohd-Azmi ML

Acta Virol., 2009;53(4):261-9.
PMID: 19941390

One-step real-time RT-PCR assay was developed for quantification of the immediate-early (IE), namely IE1 and IE2 transcripts of Rat cytomegalovirus (RCMV), strain ALL-03 in rat embryonic fibroblast cells (REF). This in-house SYBR Green I based RT-PCR was shown to have higher amplification efficiency and detection limit as compared to a commercially available real-time RT-PCR kit in quantifying these two transcripts. The quantification histogram revealed the divergence of transcription activities of the two IE genes. The IE1 transcript had a concentration peak at 7 hrs post infection (p.i.), whereas IE2 transcript at 20 hrs p.i. Regulation of IE expression is critical for determination, whether the infection is going to be abortive, lytic or latent. Therefore, this in-house developed quantitative RT-PCR assay offers an alternative for diagnosis and monitoring of the acute cytomegalovirus (CMV) infection directed at IE transcript detection.
Kimura's disease: a case report

Ng KH, Siar CH, Loh HT

Ann Dent, 1991;50(2):26-7.
PMID: 1785910

The clinical and histologic features of Kimura's disease are briefly outlined. A case presenting as a subcutaneous nodule in the region of the angle of the right mandible of a 20-year-old male is presented. The relationship of this disease to angiolymphoid hyperplasia with eosinophilia is discussed.
Genetic Association Analysis of Dopamine DRD3 Ser9Gly Polymorphism and Schizophrenia in Malay Population

Tee S, Tang P, Loh H

Iran J Public Health, 2011;40(2):6-10.
PMID: 23113067

BACKGROUND: Molecular components of the dopamine receptor (DRD3) play an important role in the pathophysiology of schizophrenia (SCZ). Previous studies have demonstrated an association between the DRD3 Ser9Gly polymorphism and SCZ but the results have been inconclusive.
METHOD: In this study, we investigated this controversial association between the Ser9Gly (A/G) polymorphism and SCZ using Malay cases-control (261 cases/157 controls) samples. PCR-RFLP was performed to genotype the distribution of the DRD3 Ser9Gly polymorphism.
RESULTS: Both healthy control and SCHZ patient groups were in of Hardy-Weinberg equilibrium for the analyzed genetic variability. There was a significant association between the genotype distribution DRD3 polymorphisms and SCZ (χ(2)= 9.359; df = 2; P = 0.009).
CONCLUSION: We believe that further studies are required to examine the association between others dopamine-related genes and the behavioral phenotypes of SCZ.
Anhedonia among patients with Major Depressive Disorder: A comparison between patients on escitalopram and healthy controls

Ng CG, Wong SK, Loh HS, Yee A

Clin Ter, 2014;165(6):e384-90.
PMID: 25524191 DOI: 10.7417/CT.2014.1778

BACKGROUND AND AIMS: Escitalopram has widely been recognized as one of the most frequently used antidepressants, with superior tolerability and great efficacy in preventing major depressive disorder (MDD) relapse and recurrence. However, anhedonia, which is a core symptom of MDD, remains difficult to treat. This study investigates the hedonic levels of MDD patients treated with Escitalopram.

MATERIALS AND METHODS: A total of 108 participants, 26 of whom with MDD on Escitalopram, were recruited in this cross sectional study. They were evaluated using the Snaith-Hamilton Pleasure Scale (SHAPS) and Beck Depression Inventory (BDI) questionnaires to assess their hedonic state, general mental health condition and level of depression.

RESULTS: Our study shows that most items in the SHAPS scores are significantly different between MDD patients on Escitalopram and the controls.

CONCLUSIONS: The hedonic capacity remains different between the two groups despite patients with MDD are put on Escitalopram treatment. Escitalopram fails to alleviate the hedonic state of MDD patients. Antidepressants that improve both depressive symptoms and hedonic states should be considered when treating MDD patients in clinical settings.
Fulltext New estimates of CMV seroprevalence in Malaysia. Where do we go from here?

Camalxaman SN, Zeenathul NA, Quah YW, Zuridah H, Loh HS

Med J Malaysia, 2012 Apr;67(2):231.
PMID: 22822655
Fulltext Linkage of schizophrenia with TPH2 and 5-HTR2A gene polymorphisms in the Malay population

Tee SF, Chow TJ, Tang PY, Loh HC

Genet. Mol. Res., 2010;9(3):1274-8.
PMID: 20623453 DOI: 10.4238/vol9-3gmr789

The serotoninergic system has been implicated in the etiology of schizophrenia and other behavioral disorders. Association studies have focused on the tryptophan hydroxylase 2 gene (TPH2) and the 5-hydroxytryptamine receptor 2A gene (5-HTR2A). We genotyped two single-nucleotide polymorphisms, A1438G of 5-HTR2A and intronic rs1386494 of TPH2 in the Malay population, using a sample size of 289 schizophrenic patients and 130 healthy controls. We found a significant association of A1438G of 5-HTR2A with schizophrenia in Malays. On the other hand, TPH2 polymorphism was not associated with schizophrenia. This is the first genetic association study concerning schizophrenia in the Malay population.
Fulltext Clinical factors associated with sexual dysfunction among men in methadone maintenance treatment and buprenorphine maintenance treatment: a meta-analysis study

Yee A, Loh HS, Hisham Hashim HM, Ng CG

Int J Impot Res, 2014 Sep-Oct;26(5):161-6.
PMID: 24990199 DOI: 10.1038/ijir.2014.18

Methadone maintenance treatment is proven to be effective treatment for opioid dependence. Of the many adverse events reported, sexual dysfunction is one of the most common side effects. However, there may be other clinical factors that are associated with sexual dysfunction among methadone users. We conducted a meta-analysis to examine the clinical factors associated with sexual dysfunction among male patients on methadone and buprenorphine treatments, of which eligible studies were selected using prior defined criteria. A total of 2619 participants from 16 eligible studies, published from inception till December 2012, were identified from the PubMed, OVID and EMBASE databases. The included studies provided prevalence estimates for sexual dysfunction among methadone users with a meta-analytical pooled prevalence of 52% (95% confidence interval (CI), 0.39-0.65). Only four studies compared sexual dysfunction between the two groups, with a significantly higher combined odds ratio in the methadone group (odds ratio=4.01, 95% CI, 1.52-10.55, P=0.0049). Our study shows that eight clinical factors are associated with sexual dysfunction among men receiving opioid substitution treatment, namely age, hormone assays, duration of treatment, methadone dose, medical status, psychiatric illness, other current substance use and familial status, and methadone versus buprenorphine treatment. Despite the methodological limitations, the findings of this meta-analysis study may offer better insights to clinicians in dealing with both sexual dysfunction and its related problems.
Fulltext The association between risk factors and hypertension in perak, malaysia

Loh KW, Rani F, Chan TC, Loh HY, Ng CW, Moy FM

Med J Malaysia, 2013 Aug;68(4):291-6.
PMID: 24145254 MyJurnal

Hypertension is a major public health problem in Malaysia. A survey was initiated to examine the association of modifiable and non-modifiable risk factors for hypertension in Perak, Malaysia.
Fulltext BDNF and DARPP-32 genes are not risk factors for schizophrenia in the Malay population

Loh HC, Tang PY, Tee SF, Chow TJ, Cheah YC, Singh SS

Genet. Mol. Res., 2012;11(1):725-30.
PMID: 22576830 DOI: 10.4238/2012.March.22.2

A number of studies have pointed to the association of BDNF (brain-derived neurotrophic factor) and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) with schizophrenia. The purpose of this study was to determine whether these two genes are involved in the pathogenesis of schizophrenia in the Malay population. Two single nucleotide polymorphisms Val66Met of BDNF, -2036C>G and g.1238delG of DARPP-32 were genotyped in the Malay population in 200 patients with schizophrenia and 256 healthy controls. Analysis of allele and genotype frequencies in these two groups revealed no significant association of BDNF or DARPP-32 polymorphisms with schizophrenia in Malays. This is the first such association study in the Malay population.
Pathogenesis and antibody response to a cytomegalovirus infection in newborn rats

Loh HS, Mohd-Azmi ML, Sheikh-Omar AR, Zamri-Saad M, Tam YJ

Acta Virol., 2007;51(1):27-33.
PMID: 17432941

The present study described the kinetics of Rat cytomegalovirus (RCMV) infection in newborn rats by monitoring infectious virus and viral antigens in various organs, viral DNA in the blood (DNAemia) and antibody response. These parameters were evaluated quantitatively using double-antibody sandwich ELISA (DAS-ELISA), real-time PCR, indirect ELISA and virus infectivity assay. For the first time DAS-ELISA was used for detection of RCMV antigen directly from organ samples. The relationships between the presence of viral antigens in the infected organs and antibody levels were established by the Spearman's rank test. It was found that the virus was present in the blood, spleen, liver, lungs, and kidneys earlier than in the salivary glands. Furthermore, the early immunity of the newborn rats led to a delayed seroconversion. We suggested that the prolonged presence of the virus in salivary glands could augment the antibody response that conversely might be responsible for a reduction of viremia. This study expanded our understanding of RCMV pathogenesis leading to improved therapeutic and preventive treatment regimens particularly for the neonatal Human cytomegalovirus (HCMV) infections. Additionally, the detection procedures developed in this study such as DAS-ELISA and real-time PCR could serve as alternative techniques for rapid screening of large number of samples.
Trigeminal neuralgia. A retrospective survey of a sample of patients in Singapore and Malaysia

Loh HS, Ling SY, Shanmuhasuntharam P, Zain R, Yeo JF, Khoo SP

Aust Dent J, 1998 Jun;43(3):188-91.
PMID: 9707784

This survey was undertaken to study the clinical features of trigeminal neuralgia in an Asian population. Demographic data of 44 patients treated at the Dental Faculty of the National University of Singapore and at the University of Malaya were reviewed. The results of the survey were analysed and comparisons made with those of Caucasian patients as reported in other studies where there was a general similarity in the clinical findings. Trigeminal neuralgia presented predominantly in females. Right-sided involvement occurred at a greater frequency, and the peak age at onset was between the sixth and seventh decades of life. The only significant variant in the present sample was the greater involvement of the mandibular branch of the trigeminal nerve rather than the maxillary division. In addition, there was a much greater representation from Chinese patients over Malays as compared with their ratios in the general population.
Characterization of a novel rat cytomegalovirus (RCMV) infecting placenta-uterus of Rattus rattus diardii

Loh HS, Mohd-Azmi ML, Lai KY, Sheikh-Omar AR, Zamri-Saad M

Arch Virol, 2003 Dec;148(12):2353-67.
PMID: 14648291

A new rat cytomegalovirus (RCMV) isolated from the placenta/uterus of a house rat (Rattus rattus diardii) was found to productively infect rat embryo fibroblast (REF) cells. The virus produced typical herpesvirus-like cytopathic effects characterized by a lytic infection. The well-known herpesvirus morphology was confirmed by electron microscopy. Its slow growth in cell culture indicated that the virus is belonging to subfamily Betaherpesvirinae. Electron microscopy techniques and immunohistochemistry confirmed the presence of herpesviral inclusion bodies and virus related particles in the cytoplasm and nucleus of infected cells. Hyperimmune serum against the Maastricht strain of RCMV revealed the virus identity in neutralization test, immunoperoxidase and immunofluorescence techniques. Despite typical characteristics of CMV, the viral genome is significantly different from that of Maastricht, English, UPM/Sg and UPM/Kn strains. The dissimilarities, which have not been reported before, had been confirmed by mean of restriction endonuclease analysis. The new RCMV strain, a virus that infects placenta and uterus of rats, has been named as ALL-03.
Fulltext Cross-reactivity of Malaysian rat cytomegalovirus strains with its human counterpart

Camalxaman SN, Zeenathul NA, Quah YW, Loh HS, Zuridah H, Sheikh-Omar AR, et al.

Trop Biomed, 2011 Dec;28(3):661-7.
PMID: 22433897 MyJurnal

This study probes into the prospect of cross-reactivity of HCMV with RCMV which has not been acknowledged to date. We describe the uncovering of a protein with an estimated size of between 61-68 kDa from local RCMV strains which reacted with HCMV positive sera. Our findings are a first disclosure of a plausible immunological cross-reactivity between RCMV with its human counterpart which grounds substantial interest implying existence of conserved determinants between rat and human CMV polypeptides. The cross-reactive protein most likely represents an enveloped glycoprotein, though the precise identification and its degree of similarity needs to be evidently defined and further elucidated in forthcoming experiments.
Collagenofibrotic glomerulopathy- report of a rare renal disease with serial biopsies

Ng YF, Chow CY, Yang WS, Lye WC, Loh HL

Malays J Pathol, 2020 Apr;42(1):131-135.
PMID: 32342943

INTRODUCTION: Collagenofibrotic glomerulopathy or collagen type-III glomerulopathy is a rare glomerular disease characterised by the deposition of type III collagen fibres in the subendothelial space and mesangium of the glomerulus.
CASE REPORT: Here, we present a case of collagenofibrotic glomerulopathy in a 49-year-old Indian female, the first to be reported from Singapore. Renal biopsy showed PAS (periodic acid-Schiff), silver and Congo red negative, amorphous extracellular material that expanded mesangial and subendothelial regions. Such materials were strongly positive for anti-collagen III immunofluorescent staining. Under electron microscopy, the mesangial and some subendothelial regions were greatly expanded by abundant collagen fibres which were different from normal collagen III fibres in both appearance and periodicity.
DISCUSSION: The availability of past renal biopsies for reference offered insight into disease progression. From the initial diagnosis of focal segmental glomerulosclerosis to eventually collagenofibrotic glomerulopathy over a time span of more than 10 years, this case highlights the gradual accumulation of collagen fibres in the glomeruli before classical features are apparent. It also emphasises the importance of electron microscopy in the diagnosis of this disease.
Fulltext Reheating of soy oil is detrimental to bone metabolism in oestrogen deficient rats

Ima-Nirwana S, Ahmad SN, Yee LJ, Loh HC, Yew SF, Norazlina M, et al.

Singapore Med J, 2007 Mar;48(3):200-6.
PMID: 17342287

The short-term and long- term effects of heated soy oil on bone metabolism in ovariectomised Sprague-Dawley rats were studied.
Acalypha wilkesiana extracts induce apoptosis by causing single strand and double strand DNA breaks

Lim SW, Ting KN, Bradshaw TD, Zeenathul NA, Wiart C, Khoo TJ, et al.

J Ethnopharmacol, 2011 Nov 18;138(2):616-23.
PMID: 22008878 DOI: 10.1016/j.jep.2011.10.005

The seeds of Acalypha wilkesiana have been used empirically by traditional healers in Southwest Nigeria together with other plants as a powder mixture to treat patients with breast tumours and inflammation.
Appendectomy and asthma: a search for an association in older subjects

Koay KL, Mohd Zim MA, Botross NP, Thong YK, Nordin N, Ramachandran A, et al.

Med J Malaysia, 2024 Jan;79(1):47-51.
PMID: 38287757

INTRODUCTION: Several risk factors found to be associated with postoperative complications and cancer surgery, which carry a significant morbidity risk to cancer patients. Therefore, prehabilitation is necessary to improve the functional capability and nutritional status of a patient prior to surgery, so that the patient can withstand any postoperative activity and associated deterioration. Thus, this study aims to assess the effectiveness of prehabilitation interventions on the functional status of patients with gastric and oesophageal cancer who underwent esophagectomy and gastrectomy.
MATERIAL AND METHODS: An interventional study was carried out among oesophageal and gastric cancer patients who had undergone surgery at the National Cancer Institute of Malaysia. The prehabilitation process took a maximum of two weeks, depending on the patient's optimisation before surgery. The prehabilitation is based on functional capacity (ECOG performance status), muscle function (handgrip strength), cardio-respiratory function (peak flow meter) and nutritional status (calorie and protein). Postoperative outcomes are measured based on the length of hospital stay, complications, and Clavien-Dindo Classification.
RESULTS: Thirty-one patients were recruited to undergo a prehabilitation intervention prior to gastrectomy (n=21) and esophagectomy (n=10). Demographically, most of the cancer patients were males (67.7%) with an ideal mean of BMI (23.5±6.0). Physically, the majority of them had physical class (ASA grade) Grade 2 (67.7%), ECOG performance status of 1 (61.3%) and SGA grade B (51.6%). The functional capacity and nutritional status showed a significant improvement after one week of prehabilitation interventions: peak expiratory flow meter (p<0.001), handgrip (p<0.001), ECOG performance (p<0.001), walking distance (p<0.001), incentive spirometry (p<0.001), total body calorie (p<0.001) and total body protein (p=0.004). However, those patients who required two weeks of prehabilitation for optimization showed only significant improvement in peak expiratory flow meter (p<0.001), handgrip (p<0.001), and incentive spirometry (p<0.001). Prehabilitation is significantly associated postoperatively with the length of hospital stay (p=0.028), complications (p=0.011) and Clavien-Dindo Classification (p=0.029).
CONCLUSION: Prehabilitation interventions significantly increase the functional capacity and nutritional status of cancer patients preoperatively; concurrently reducing hospital stays and complications postoperatively. However, certain cancer patients might require over two weeks of prehabilitation to improve the patient's functional capacity and reduce complications postoperatively.

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