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Fulltext An audit of intraoperative frozen section in Johor

Khoo JJ

Med J Malaysia, 2004 Mar;59(1):50-5.
PMID: 15535336 MyJurnal

A 4-year-review was carried out on intraoperative frozen section consultations in Sultanah Aminah Hospital, Johor Bahru. Two hundred and fifteen specimens were received from 79 patients in the period between January 1999 and December 2002. An average of 2.72 specimens per patient was received. The overall diagnostic accuracy was high, 97.56%. The diagnoses were deferred in 4.65% of the specimens. False positive diagnoses were made in 3 specimens (1.46%) and false negative diagnoses in 2 specimens (0.98%). This gave an error rate of 2.44%. The main cause of error was incorrect interpretation of the pathologic findings. In the present study, frozen sections showed good sensitivity (97.98%) and specificity (97.16%). Despite its limitations, frozen section is still generally considered to be an accurate mode of intraoperative consultation to assist the surgeon in deciding the best therapeutic approach for his patient at the operating table. The use of frozen section with proper indications was cost-effective as it helped lower the number of reoperations. An audit of intraoperative frozen section from time to time serves as part of an ongoing quality assurance program and should be recommended where the service is available.
Fulltext A study of proliferating cell nuclear antigen expression in benign, borderline and malignant epithelial tumours of ovary

Khoo JJ

Med J Malaysia, 2002 Jun;57(2):161-8.
PMID: 24326646

Borderline epithelial tumours or low malignant potential epithelial tumours of ovary have a better prognosis and hence it is important to distinguish this group from their malignant counterparts. Several studies were done correlate the growth rates of tumours with nuclear proteins that are expressed in proliferating cells. Immunohistochemical stains with monoclonal antibodies against proliferating cell nuclear antigen (PCNA) were used on 51 archival epithelial tumours of ovary. The percentage of PCNA reactivity showed means of 1.1%, 2.3% and 27.7% with benign, borderline tumours and malignant epithelial tumours of ovary. respectively. The % PCNA reactivity was found to be significantly different amongst the three group (p<0.001). Thus , PCNA reactivity can help to differentiate borderline tumours from malignant epithelial tumours of ovary. This is critical when light microscopic appearances are equivocal and therapeutic management is dependent on the diagnosis.
Fulltext Angiosarcoma of the liver

Khoo JJ

Med J Malaysia, 2002 Jun;57(2):233-6.
PMID: 24326660

A 47-years-old Malay man presented with unremitting epigastric pain and loss weight for 3 months. At laparotomy, a large tumour mas was found in the liver and a few small nodules in the spleen. Histopathological examination revealed a hepatic angiosarcoma with metastsis to the spleen. He had exposure to formic acid fumes for more than 23 years in his work as a rubber tapper. The various chemical carcinogens that are implicated in this type of tumour are discussed. The possiblity of an association between formic acid fumes and development of angiosarcoma in the liver is highlighted.
Fulltext Renal biopsies in Johor: a 7-year study

Khoo JJ

Malays J Pathol, 2001 Dec;23(2):101-4.
PMID: 12166589

Consecutive renal biopsies received from 1994 to 2000 in Johor Bahru were reviewed. There were 441 cases, of which 407 were adequate biopsies (92.3%). Lupus nephritis formed the largest diagnostic entity (126 cases, 31.0%). This reflected the high prevalence of systemic lupus erythematosus (SLE) patients in Malaysia. The most common histological pattern of lupus nephritis was diffuse proliferative glomerulonephritis: WHO Class IV (96 cases, 76.2%). Other diagnostic entities were minimal change disease (28.5%), proliferative glomerulonephritis (10.6%), IgA nephropathy (9.8%), focal glomerulosclerosis (4.9%), membranous glomerulonephritis (4.4%), transplant rejection (3.9%), end stage nephropathy (3.4%) and others (3.4%). The morphological pattern of renal biopsies in Johor was similar to that reported in the University Hospital Kuala Lumpur.
Fibrolamellar hepatocellular carcinoma: a case report

Khoo JJ, Clouston A

Malays J Pathol, 2001 Dec;23(2):115-8.
PMID: 12166592

A 6-year-old Malay boy presented with fever and abdominal pain for 2 months. Computerised tomography showed a nodular mass in the left lobe of the liver. There was also portal vein thrombosis on the left side. Serum alpha-fetoprotein was not elevated and Hepatitis B antigen was negative. Biopsy of the liver mass led to a histological diagnosis of fibrolamellar hepatocellular carcinoma. In view of extensive tumour involvement, he could not be operated on but was treated with chemotherapy. However, the tumour did not respond. While this is expected for fibrolamellar hepatocellular carcinoma, the possibility of the tumour having a component of ordinary hepatocellular carcinoma could not be excluded as the tumour was not resected. Fibrolamellar hepatocellular carcinoma is a rare histological subtype of hepatocellular carcinoma, associated with a better prognosis. It affects the younger age group and has no association with cirrhosis, hepatitis B virus infection or exposure to oral contraceptives, all of which are implicated in ordinary hepatocellular carcinoma. Serum alpha-fetoprotein level is usually within normal limits and other laboratory values are not contributory to the diagnosis. The diagnosis is usually suggested by radiographic studies viz. CT scan of the abdomen, which would show an irregular non-homogenous mass in the liver, and confirmed by histological examination. The most characteristic microscopical feature is fibrosis arranged in a lamellar fashion around polygonal and deeply eosinophilic neoplastic hepatocytes.
Fulltext A report of two non-AIDS associated Kaposi's sarcoma in Malaysia

Choon SE, Khoo JJ

Med J Malaysia, 1997 Dec;52(4):437-40.
PMID: 10968124

Kaposi's sarcoma is an uncommon cutaneous neoplasm seen classically in elderly males of East European or Jewish extract. It has been known to be endemic in sub-Saharan Africa for many years. Numerous cases had been described in patients on long-term immunosuppressive therapy and in patients living with acquired immunodeficiency syndrome (AIDS). In spite of the increasing number of organ transplant recipients and people living with AIDS. Kaposi's sarcoma remains rare in Asia. We report two cases seen in Johor, Malaysia.
Fulltext Rhinosporidiosis presenting as recurrent nasal polyps

Khoo JJ, Kumar KS

Med J Malaysia, 2003 Jun;58(2):282-5.
PMID: 14569751 MyJurnal

Rhinosporidiosis is a chronic granulomatous disease of the mucous membrane, predominantly of the nose and nasopharynx. It is uncommon in Malaysia but has been seen in immigrant workers from endemic areas like India and Sri Lanka. A case seen in Johor is reported here to highlight the need of awareness among clinicians at a time where there is increasing numbers of immigrant workers in our country. The causative organism of this disease is Rhinosporidium seeberi, which is found in stagnant waters. Sporangia and endospores of R. seeberi are seen in the granulomatous polypoidal lesions. The patients commonly present with epistaxis and nasal blockage. Complete excision is the treatment of choice for this disease. Recurrences are common despite anti-microbial treatment.
Coccidioidomycosis in malaysia

Choon SE, Khoo JJ

Br J Dermatol, 1999 Mar;140(3):557-8.
PMID: 10233296
Fulltext Pattern of hMLH1, hMSH2 and hMSH6 expression and clinical characteristics in a sample of Malaysian colorectal carcinoma cases

Khoo JJ, Gunn A, Peh SC

Malays J Pathol, 2013 Jun;35(1):45-57.
PMID: 23817394 MyJurnal

Malignant transformation from normal colonic mucosa to carcinomas may be accelerated by genetic loss or inactivation of genes of the DNA mismatch repair system. The aim of the study was to determine the local incidence and pattern of immunohistochemical expression of mismatch repair proteins namely: hMLH1, hMSH2 and hMSH6 in a series of colorectal carcinomas (CRCs) and correlate this to their clinical and pathological features. Forty-three out of 298 cases of CRCs (14.4%) showed abnormal staining pattern for mismatch repair proteins with a majority (65.1%) showing single hMLH1 loss. Tumours with mismatch repair defect (MMR-d) were frequently found at the right side of colon (p<0.001), poorly differentiated carcinomas (p<0.001), produced more mucin (p=0.007), exophytic growth (p=0.007) and were bigger (p=0.002) than tumours with no mismatch repair defect. Immunohistochemical stains for mismatch repair proteins could be done in local laboratories on these selected cases before referring for the expensive molecular test.
Fulltext Pancreatitis leading to retroperitoneal fibrosis and ureteric obstruction

Tan HM, Khoo J, Pang KP

Med J Malaysia, 2003 Jun;58(2):286-9.
PMID: 14569752

Two patients who had acute pancreatitis subsequently developed characteristic appearance on urography of smooth extrinsic narrowing and medial deviation of the right ureter suggestive of retroperitoneal fibrosis (RPF) resulting in ureteric obstruction. Both these patients had clinical, biochemical and sonographic evidence of acute pancreatitis. CT scan of the abdomen performed on the second patient also documented acute pancreatitis. Intravenous urograms were consistent with ureteric obstruction due to retroperitoneal fibrosis. Both cases were treated conservatively. They were well after an average of 20 months. These 2 cases illustrate the uncommon association between pancreatitis and RPF.
Lupus nephritis in children in Malaysia

Khoo JJ, Pee S, Thevarajah B, Yap YC, Chin CK

J Paediatr Child Health, 2005 Jan-Feb;41(1-2):31-5.
PMID: 15670221 DOI: 10.1111/j.1440-1754.2005.00532.x

OBJECTIVES: To determine the pattern of renal histology, clinical outcome of children with lupus nephritis and to identify any associated risk factors predicting renal failure in these children.
METHODS: Retrospectively, 27 children under 16 years of age with lupus nephritis who had renal biopsies done at Sultanah Aminah Hospital Johor, Malaysia from 1994 to 2002 were studied. The renal histology was graded according to WHO classification system (1982). The medical records, laboratory data and the clinical outcome of the patients were studied.
RESULTS: There were 24 cases of WHO Class IV, two cases of WHO Class II and a case of WHO Class V. Twenty children were in the good renal outcome group while six children progressed into the poor renal outcome group and required renal replacement. One child was lost to follow-up. All six children in the poor renal outcome group had WHO Class IV histology. The 5-year patient and renal survival rates were 84% and 75%, respectively. Age, sex, activity and chronicity indices in the renal histology, anaemia, elevated serum creatinine, depressed levels of C3 and C4, heavy proteinuria or presence of urinary active sediments were not associated with progression to renal failure.
CONCLUSIONS: Presently, children with lupus nephritis appeared to have better patient and renal survival rates. Assessment of renal histology in these children was important for diagnosis, treatment and probably prognosis. In this study, there was a 25% incidence of loss of renal function over 5 years in children with WHO Class IV renal histology.
Fulltext Biopsy-proven childhood glomerulonephritis in Johor

Khoo JJ, Pee S, Thevarajah B, Yap YC, Chin CK

Med J Malaysia, 2004 Jun;59(2):218-25.
PMID: 15559173 MyJurnal

Background: There has been no published study of biopsy proven childhood glomerulonephritis in Malaysia.
Objectives: To determine the pattern of childhood glomerulonephritis in Johor, Malaysia from a histopathological perspective and the various indications used for renal biopsy in children.
Materials and methods: Retrospective study was done of all renal biopsies from children under 16 years of age, received in Sultanah Aminah Hospital, Johor between 1994 and 2001. The histopathological findings were reviewed to determine the pattern of biopsy proven glomerulonephritis. The indications of biopsy, mode of therapy given after biopsy and the clinical outcome were studied.
Results: 123 adequate biopsies were received, 9 children had repeated biopsies. Of the 113 biopsies, minimal change disease formed the most common histopathological diagnosis (40.7%) while lupus nephritis formed the most common secondary glomerulonephritis (23.0%). The main indications for biopsy were nephrotic syndrome (50.8%), lupus nephritis (25.4%) and renal impairment (13.1%). The mode of therapy was changed in 59.8% of the children. Of 106 patients followed up, 84 children were found to have normal renal function in remission or on treatment. 4 patients developed chronic renal impairment and 16 reached end stage renal disease. Five of the 16 children with end stage disease had since died while 11 were on renal replacement therapy. another 2 patients died of other complications.
Conclusions: The pattern of childhood GN in our study tended to reflect the more severe renal parenchymal diseases in children and those requiring more aggressive treatment. This was because of our criteria of selection (indication) for renal biopsy. Renal biopsy where performed appropriately in selected children may not only be a useful investigative tool for histological diagnosis and prognosis but may help clinicians plan the optimal therapy for these children.
Fulltext Endometriosis of the appendix presenting as acute appendicitis

Khoo JJ, Ismail MS, Tiu CC

Singapore Med J, 2004 Sep;45(9):435-6.
PMID: 15334288

While endometriosis is fairly common, endometriosis of the appendix is a very rare occurrence. Correct pre-operative diagnosis is uncommon and definitive diagnosis is established by histology of the appendix. We present a case of endometriosis of the appendix that manifested as acute appendicitis in a 40-year-old woman.
Culturable pathogenic bacteria in ticks parasitizing farm animals and rodents in Malaysia

Loong SK, Lim FS, Khoo JJ, Lee HY, Suntharalingam C, Ishak SN, et al.

Trop Biomed, 2020 Sep 01;37(3):803-811.
PMID: 33612793 DOI: 10.47665/tb.37.3.803

Ticks are vectors of bacteria, protozoa and viruses capable of causing serious and life threatening diseases in humans and animals. Disease transmission occurs through the transfer of pathogen from tick bites to susceptible humans or animals. Most commonly known tick-borne pathogens are obligate intracellular microorganisms but little is known on the prevalence of culturable pathogenic bacteria from ticks capable of growth on artificial nutrient media. One hundred and forty seven ticks originating from dairy cattle, goats and rodents were collected from nine selected sites in Peninsular Malaysia. The culture of surfacesterilized tick homogenates revealed the isolation of various pathogenic bacteria including, Staphylococcus sp., Corynebacterium sp., Rothia sp., Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli and Bacillus sp. and its derived genera. These pathogens are among those that affect humans and animals. Findings from this study suggest that in addition to the regular intracellular pathogens, ticks could also harbor extracellular pathogenic bacteria. Further studies, hence, would be needed to determine if these extracellular pathogens could contribute to human or animal infection.
pSTAT3 and MYC in Epstein-Barr virus-positive diffuse large B-cell lymphoma

Teoh SH, Khoo JJ, Abdul Salam DSD, Peh SC, Cheah SC

Malays J Pathol, 2019 Dec;41(3):273-281.
PMID: 31901912

INTRODUCTION: Epstein-Barr Virus (EBV) is associated with several B-cell non-Hodgkin's lymphoma (NHL), but the role of EBV in diffuse large B-cell lymphoma (DLBCL) is poorly defined. Several studies indicated the expression of phosphorylated STAT3 (pSTAT3) is predominant in EBV(+)- DLBCL, of which its activated form can promote the downstream oncogenes expression such as c-MYC. c-MYC gene rearrangements are frequently found in aggressive lymphoma with inferior prognosis. Furthermore, EBV is a co-factor of MYC dysregulation. JAK1/STAT3 could be the downstream pathway of EBV and deregulates MYC. To confirm the involvement of EBV in JAK1/ STAT3 activation and MYC deregulation, association of EBV, pSTAT3 and MYC in EBV(+)- DLBCL cases were studied. The presence of pSTAT3 and its upstream proteins: pJAK1 is identify to delineate the role of EBV in JAK1/STAT3 pathway.
MATERIALS AND METHODS: 51 cases of DLBCL paraffin-embedded tissue samples were retrieved from a single private hospital in Kuala Lumpur, Malaysia. EBER-ISH was performed to identify the EBV expression; ten EBV(+)-DLBCL cases subjected to immunohistochemistry for LMP1, pJAK1, pSTAT3 and MYC; FISH assay for c-MYC gene rearrangement.
RESULTS: Among 10 cases of EBV(+)-DLBCL, 90% were non-GCB subtype (p=0.011), 88.9% expressed LMP1. 40% EBV(+)-DLBCL had pJAK1 expression.
CONCLUSION: 66.7% EBV(+)-DLBCL showed the positivity of pSTAT3, which implies the involvement of EBV in constitutive JAK/STAT pathway. 44.5% EBV(+)-DLBCL have co-expression of pSTAT3 and MYC, but all EBV(+)-DLBCL was absence with c-MYC gene rearrangement. The finding of clinical samples might shed lights to the lymphomagenesis of EBV associated with non-GCB subtypes, and the potential therapy for pSTAT3-mediated pathway.
Seroprevalences and their associated predictors of chikungunya, dengue, Japanese encephalitis and zika among forest fringe dwellers of Peninsular Malaysia

Khor CS, Lee HY, Abd-Majid MA, Khoo HY, Khoo JJ, AbuBakar S

Trop Biomed, 2024 Jun 01;41(2):224-229.
PMID: 39154278 DOI: 10.47665/tb.41.2.015

Serological evidence has shown the presence of several mosquito-borne arbovirus infections among the inhabitants of the forest fringe areas of the tropics. Among these infections, Japanese encephalitis, dengue fever, chikungunya fever and Zika fever could be targeted for vaccination to overcome severe infection and limit the disease transmission. Seroprevalence data among this high-risk population are needed to provide an estimate of the potential cost-effectiveness of any vaccine programme targeting these infections. The present study was conducted at six indigenous people (Orang Asli) villages and FELDA (Federal Land Development Authority) settlements located at the forest fringes of Malaysia. All participants consented and provided blood samples and demographic data for the study. The blood samples were tested for the presence of antibodies against CHIKV, DENV, JEV and ZIKV individually using ELISA. Results obtained were also analysed to determine the predictors for CHIKV, DENV, JEV and ZIKV seropositivity. Among the 585 samples tested, 33.0% (N=193), 41.7% (N=244), 10.3% (N=60) and 21.0% (N=123) were positive for CHIKV IgG, DENV IgG, JEV IgG and ZIKV IgG, respectively. Approximately one-third (N=220, 37.6%) of the participants were tested negative for IgG antibodies against all four arboviruses. Age of participants and type of settlement were found to be a significant predictor for CHIKV, DENV, JEV and ZIKV seropositivity. Level of education was a significant predictor for CHIKV, DENV and ZIKV seropositivity. Gender, however, was not found to be a significant predictor for infection with any of these viruses. These findings reaffirmed the significant presence of infection involving these major arboviruses among the group of people living within the forest fringe areas of Peninsular Malaysia. Hence, any future consideration of vaccination for these infections must take into consideration the marginalized and underserved communities living at the forest fringe areas of the tropics where these infections are present.
Bacterial profiling of head lice isolated from the Orang Asli: A first report in Malaysia

Abd Majid MA, Khoo JJ, Lim FS, Khor CS, Loong SK, Low VL, et al.

Trop Biomed, 2020 Dec 01;37(4):884-895.
PMID: 33612742 DOI: 10.47665/tb.37.4.884

This study was carried out to determine from bacterial profiling to the bacterial profiles of head lice among the Orang Asli communities. The head lice were collected from Orang Asli community volunteers. The surface sterilized head lice pools were subjected to genomic DNA extraction while next generation sequencing of the 16S rRNA gene was performed using the Illumina MiSeq platform. Six female and three male head lice identified as Pediculus humanus capitis were collected. A total of 111 368 number of NGS sequencing reads were recorded while another 223 bacterial taxa sequences were obtained. Symbiotic bacteria showed the highest number of reads, with Arsenophonus and Rhodococcus sequences being the most abundant genera in the female and male samples, respectively. The female head lice contained a more distinct microbial diversity. Amongst the pathogenic bacterial species sequences noted were the methicillin-resistant Staphylococcus aureus, Streptobacillus moniliformis, Haemophilus influenzae, Bordetella pertussis and Acinetobacter baumannii. The 16S rRNA genome sequencing revealed a number of rare and pathogenic bacterial species within the head lice of the Orang Asli. The socio-economic practices of the community which involved forest foraging and hunting, and their poor living conditions potentially facilitated the transmission of zoonotic bacterial pathogens, including those found within the head lice. Hence, there is the possibility that the head lice could serve as vectors for the transmission of pathogenic bacteria. This study highlighted the diverse microbial community found within the head lice's gut of the Orang Asli, with the detection of multiple rare and pathogenic bacteria capable of causing severe infections.
Detection in Malaysia of a Borrelia sp. From Haemaphysalis hystricis (Ixodida: Ixodidae)

Khoo JJ, Lim FS, Tan KK, Chen FS, Phoon WH, Khor CS, et al.

J Med Entomol, 2017 09 01;54(5):1444-1448.
PMID: 28874019 DOI: 10.1093/jme/tjx131

Spirochetes from the Borrelia genus are known to cause diseases in humans, namely Lyme disease and relapsing fever. These organisms are commonly transmitted to humans by arthropod vectors including ticks, mite, and lice. Here, we report the molecular detection of a Borrelia sp. from a Haemaphysalis hystricis Supino tick collected from wildlife in an Orang Asli settlement in Selangor, Malaysia. Phylogenetic analyses of partial 16s rRNA and flaB gene sequences revealed that the Borrelia sp. is closely related to the relapsing fever group borreliae, Borrelia lonestari, Borrelia miyamotoi, and Borrelia theileri, as well as a number of uncharacterized Borrelia sp. from ticks in Portugal and Japan. To our knowledge, this is the first report of a Borrelia sp. detected in H. hystricis, and in Malaysia. The zoonotic potential of this Borrelia sp. merits further investigation.
Fulltext Alterations of haemodynamic parameters in spontaneously hypertensive rats by Aristolochia ringens Vahl. (Aristolochiaceae)

Aigbe FR, Munavvar ASZ, Rathore H, Eseyin O, Pei YP, Akhtar S, et al.

J Tradit Complement Med, 2018 Jan;8(1):72-80.
PMID: 29321992 DOI: 10.1016/j.jtcme.2017.02.006

Aristolochia ringens Vahl. (Aristolochiaceae (AR); mǎ dōu líng) is used traditionally in Nigeria for the management of various disorders including oedema. Preliminary investigation revealed its modulatory effect on the cardiovascular system. This study was aimed at investigating the effect of the aqueous root extract of A. ringens (AR) on haemodynamic parameters of spontaneously hypertensive rats (SHRs). The effect of oral subacute (21 days) and intravenous acute exposure of SHRs to the extract were assessed using tail cuff and carotid artery canulation methods respectively. In the latter, the effect of chloroform, butanol and aqueous fractions of AR were also evaluated. The extract significantly reduced systolic and diastolic blood pressures in SHRs, with peak reductions of 20.3% and 26.7% respectively at 50 mg/kg by the 21st day of oral subacute exposure. Upon intravenous exposure, AR (50 mg/kg) reduced systolic and diastolic blood pressure by as much as 53.4 ± 2.2 and 49.2 ± 2.8 mmHg respectively. A dose-dependent reduction in heart rate, significant at 25 and 50 mg/kg was also observed. Hexamethonium (20 mg/kg) and atropine (1 mg/kg) inhibited the extract's reduction of systolic blood pressure, diastolic blood pressure and heart rate significantly. The extract's butanol fraction produced the greatest systolic and diastolic blood pressures reduction of 67.0 ± 3.8 and 68.4 mmHg respectively at 25 mg/kg and heart rate reduction of 40 ± 7 beats per minute at 50 mg/kg. HPLC analysis revealed the presence of 4-hydroxybenzoic acid and quercetin in AR. The extract's alterations of haemodynamic parameters in this study show that it has hypotensive effect on spontaneously hypertensive rats.
Fulltext Ministry of health clinical practice guidelines: cancer screening

Lee HP, Chew CT, Consigliere DT, Heng D, Huang DT, Khoo J, et al.

Singapore Med J, 2010 Feb;51(2):170-3; quiz 174-5.
PMID: 20358158

The Ministry of Health publishes national clinical practice guidelines to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with key recommendations from the guidelines) from the Ministry of Health clinical practice guidelines on cancer screening, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov. sg/mohcorp/publications.aspx?id=24018). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

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