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Epidemiology of neonatal pneumothorax developed spontaneously and during respiratory supports in neonatal intensive care units

Boo NY, Lee Ang EL, The Malaysian National Neonatal Registry

Malays J Pathol, 2023 Dec;45(3):441-456.
PMID: 38155385

BACKGROUND: Information on incidence and risk factors associated with different types of neonatal pneumothorax were lacking globally.
OBJECTIVES: To determine incidences of pneumothorax developed spontaneously and during different modes of respiratory support, and risk factors associated with each type of pneumothorax.
STUDY DESIGN: Retrospective observational study of neonates in the Malaysian National Neonatal Registry.
SETTING: 44 Malaysian neonatal intensive care units (NICUs).
PARTICIPANTS: All neonates born in 2015-2020 and admitted to NICUs.
RESULTS: Pneumothorax developed in 3265 neonates: 37.5% occurred spontaneously, 62.5% during respiratory support. The incidence of all types of pneumothorax was 1.75 per 1000 livebirths, and of spontaneous pneumothorax was 0.58 per 1000 livebirths. Pneumothorax developed in 0.6% (450/70512) of neonates during continuous positive air way pressure therapy (nCPAPt), 1.8% (990/54994) of neonates during conventional mechanical ventilation (CMV), and 7.0% (599/8557) of neonates during high frequency ventilation (HFV). Term neonates had significantly higher pneumothorax rate than preterms (p<0.001). Multiple logistic regression analyses show that exposure to intermittent positive pressure ventilation and chest compression at birth were significant independent factors associated with increased risk of spontaneous pneumothorax and CMV, and persistent pulmonary hypertension was associated with increased risk of spontaneous pneumothorax and pneumothorax during CMV and HFV.
CONCLUSIONS: The most common type of pneumothorax was spontaneous in-onset. Neonates on HFV had the highest and those on nCPAPt the lowest rate of pneumothorax. Improving training of resuscitation techniques at birth and strategies of use of invasive modes of respiratory support may reduce incidences of all types of pneumothorax.
Diagnosis and surveillance of dengue virus infections: gold standards and new directions

Cardosa MJ

Malays J Pathol, 1989 Aug;11:7-10.
PMID: 2698983
CIP2A expression in high grade prostatic intraepithelial neoplasia and prostate adenocarcinoma: a tissue mıcroarray study

Celikden SG, Baspinar S, Ozturk SA, Karaibrahimoglu A

Malays J Pathol, 2020 Aug;42(2):227-236.
PMID: 32860375

INTRODUCTION: CIP2A is an oncoprotein involved in the progression of several human malignancies. It has recently been described as a prognostic marker in many cancers. The present study aimed to investigate the immunohistochemical expression of CIP2A in benign prostatic hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PC), and to analyse the association with the clinicopathological parameters in PC cases to define its role in the development and progression of PC.
MATERIALS AND METHODS: Immunohistochemical staining for CIP2A was performed on the tissue microarray sections of 105 PC, 27 HGPIN and 27 BPH tissues. The CIP2A expression scores were compared with several clinicopathological parameters.
RESULTS: CIP2A was expressed in 96,2% of PC, 55,6% of HGPIN and 40,7% of BPH tissues. The expression of CIP2A in PC was significantly higher than in HGPIN (p<0.0001) and BPH (p<0.0001) cases. CIP2A expression score was significantly associated with Gleason score (p=0.032) and lymphovascular invasion (p=0.039). Nevertheless, there was no statistically significant association between the expression of CIP2A and perineural invasion, pT stage, metastasis and recurrence (p>0.05). Multivariate analysis indicated that GS, lymphovascular invasion, distant metastasis were independent prognostic factors for PC patients but, CIP2A expression score was not found to be a prognostic factor. Additionally, there was no significant difference between the survival times of patients according to CIP2A expression (p=0.174).
CONCLUSIONS: According to our results, the expression of CIP2A protein is increased in PC and its expression may be involved in the development, differentiation, and aggressiveness of PC. However, further studies are needed to confirm our findings and to clarify the role of CIP2A in the development of PC.
The journey of Malaysian external quality assurance program for general diagnostic histopathology

Ch'ng ES, Othman NH

Malays J Pathol, 2021 Apr;43(1):19-23.
PMID: 33903301

International Academy of Pathology, Malaysian Division has initiated and run the external quality assurance program for general diagnostic histopathology since the year 2017. This article introduces the educational philosophy of this external quality assurance program and the technicalities in running such a national program. Challenges in ensuring the successful running of this program to gain wide acceptance by histopathology laboratories in Malaysia as well as experience in overcoming these challenges are detailed. This article charts the future direction of this external quality assurance program.
Low cost immunohistochemistry bench for developing countries

Ch'ng ES, Khiro FI

Malays J Pathol, 2018 Aug;40(2):209-211.
PMID: 30173241

No abstract available.
The immunoassay services in Malaysia

Ch'ng SL

Malays J Pathol, 1983 Aug;6:21-5.
PMID: 6599865
The pattern of lymphoma in east Malaysian patients as experienced in the University Hospital, Kuala Lumpur

Chai SP, Peh SC, Kim LH, Lim MY, Gudum HR

Malays J Pathol, 1999 Jun;21(1):45-50.
PMID: 10879278

Lymphoma is a highly heterogeneous group of malignant disease. This study aimed to elucidate the pattern of lymphoma in the East Malaysian patient population. 107 cases of confirmed lymphomas from East Malaysian biopsy material were retrieved from the files of the Department of Pathology, University of Malaya, in the 3-year period between 1981 to 1983. With the use of a panel of lymphoid antibodies, the disease was sub-classified using the Rye classification for Hodgkin's lymphoma (HL) and the REAL classification for non-Hodgkin's lymphoma (NHL). All of the cases were tested for the presence of the Epstein-Barr virus by EBER-ISH. There were 11 (10.3%) HL, 80 (74.7%) B-NHL and 16 (15%) T-NHL. The HL:NHL ratio was 1:9. The most common tumour in children was Burkitt's lymphoma 7/13 (53.8%). In the adult group, there were 72/94 (76.6%) B-NHL ¿diffuse large cell type 51 (of which 2 were CD30+), Burkitt's lymphoma 8, follicular lymphoma 5, low grade MALT 2, mantle cell type 1 and not otherwise specified due to poor morphology 5¿, 13/94 (13.8%) T-NHL and 9/94 (9.6%) HL. Of the 9 adult HL, the most common subtype was nodular sclerosis (6, 66.7%). The EBER positive rate in classical HL, T-NHL, BL and B-NHL were 33.3%, 56.3%, 60.0% and 3.1% respectively. In conclusion, the spectrum of lymphoma seen in East Malaysia was rather similar to West Malaysia except for the very low prevalence of peripheral T-cell lymphoma (PTCL) in Sarawak (3.3%).
Fulltext Disseminated histoplasmosis mimicking miliary tuberculosis: a case report

Chan KS, Looi LM, Chan SP

Malays J Pathol, 1993 Dec;15(2):155-8.
PMID: 8065179

A 35-year-old Chinese man who was known to have insulin-dependent diabetes mellitus was admitted for fever and weight loss. During his hospital stay, he fell to his death from his ward at the twelfth floor. The clinical features, radiological findings and gross organ changes at autopsy closely simulated miliary tuberculosis. Histology, however, revealed extensive necrosis of the adrenal glands, lungs, spleen, kidneys and thyroid associated with the presence of Histoplasma capsulatum organisms. This case highlights the similarity both clinically and pathologically between histoplasmosis and tuberculosis and emphasizes the need to be aware of this infection in a nonendemic area among patients with a compromised immune system.
Blood cholinesterase levels in the elderly and newborn

Chan L

Malays J Pathol, 1995 Dec;17(2):87-9.
PMID: 8935132

The spectrophotometric method of Ellman was used to determine cholinesterase (ChE) levels in plasma and whole blood in elderly patients and umbilical cord blood of newborn infants. The mean +/- SD for plasma and whole blood ChE levels were 2.24 +/- 0.58 micromol/min/ml and 4.38 +/- 0.65 micromol/min/ml respectively in a group of healthy elderly patients (n = 25). The mean +/- SD for plasma and whole blood ChE levels were 2.23 +/- 0.77 and 3.31 +/- 0.56 respectively in cord blood of healthy full term newborn infants (n = 25). In a group of healthy adult blood donors the general mean +/- SD for plasma and whole blood ChE have been shown to be 2.71 +/- 0.75 and 4.87 +/- 0.73 micromol/min/ml respectively. Statistical analysis revealed that the mean levels of plasma and whole blood ChE in elderly, newborn infants and adults were different (p < 0.001). However, there was no statistical difference between the mean level of plasma ChE in elderly and cord blood but each shared statistically significant difference when compared to the mean level in adults. The mean activity of whole blood ChE in the 3 groups was different from one another. Theoretically, decreased levels of ChE would suggest a careful assessment of drugs that are hydrolysed by ChE.
Blood cholinesterase levels in a group of Malaysian blood donors

Chan L, Balabaskaran S, Delilkan AE, Ong LH

Malays J Pathol, 1994 Dec;16(2):161-4.
PMID: 9053566

Data on blood cholinesterase levels in the Malaysian population is lacking. The spectrophotometric method of Ellman was used to determine the red cell, plasma and whole blood cholinesterase (ChE) levels in 407 Malaysian blood donors. The mean+1SD for plasma ChE in females (n = 48) was 2.37 + 0.70 umol/min/ml and 2.76 + 0.75 umol/min/ml in males (n = 359). The mean plasma ChE in males was higher than in females (p < 0.001). The mean+1SD for red cell ChE in females was 9.01 + 1.20 umol/min/ml whereas in males it was 7.69 +1.30 umol/min/ml (the mean red cell ChE in females was higher than in males, p < 0.0001). The mean+1SD for whole blood ChE for females was 4.31+ 0.58 umol/min/ml and for males it was 4.95 + 0.71 umol/min/ml. The mean whole blood ChE in males was higher than in females (p < 0.0001). Sex influenced the plasma, red cell and whole blood ChE. In males the plasma ChE was affected by the race factor. The mean+1SD plasma ChE for the Malay, Chinese and Indian were 2.92 + 0.80, 2.73 + 0.71 and 2.61+ 0.73 respectively (p < 0.002). The age factor in males affected the red cell ChE with 7.88 + 1.32 in the (30-69) age group and 7.47 + 1.23 in the (15-29) age group (p < 0.005). The whole blood ChE in females was affected by blood groups. The mean+1SD whole blood ChE for blood groups A,B and O were 4.19 + 0.42, 3.93 + 0.46 and 4.49 + 0.62 respectively (p < 0.03). The significant difference is between the ChE of group B and O, but the ChE of group A could not be determined to be different from group B or O. These results serve as guidelines for our local population in the evaluation of cholinesterase levels with regard to pesticide poisoning, liver biosynthetic capacity and unusual sensitivity to succinylcholine.
Enterovirus 71 infection induces apoptosis in Vero cells

Chan YF, Abubakar S

Malays J Pathol, 2003 Jun;25(1):29-35.
PMID: 16196375

The effects of Enterovirus 71 (HEV71) infection on African green monkey kidney cells (Vero) were investigated. It was found that the infected cells showed progressive cellular morphological changes characteristic in apoptotic cells within 10 hours post-infection. The number of apoptotic cells correlated significantly with the number of HEV71 antigen positive cells when cells were labeled using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) and stained for HEV71 antigen. Approximately 11, 26, 45 and 50% of the infected cells were apoptotic at 12, 24, 48 and 72 hours post-infection, respectively. Internucleosomal DNA fragmentation, characteristic in the late stage of apoptosis was noted beginning on day 2 post-infection. The DNA fragmentation, however, was absent in cells treated with the heat- and ultraviolet light-inactivated virus inocula. These results demonstrate the capacity of HEV71 to induce apoptosis in the infected cells. The induction, however, requires high level of HEV71 infectivity and the presence of live virus particles, suggesting the need for the presence of specific viral proteins for apoptosis to occur.
Microfilaria in hydrocele fluid cytology

Chandran PA, Jayaram G, Mahmud R, Anuar AK

Malays J Pathol, 2004 Dec;26(2):119-23.
PMID: 16329565

Filariasis, a parasitic infection endemic in parts of India, Myanmar, islands of the South Pacific, West and East Africa and Saudi Arabia can be diagnosed from various types of cytopathological specimens. This case documents the detection of filarial infection from hydrocele fluid cytology in a 30-year-old Myanmar migrant worker in Malaysia.
The chemical pathology laboratory services in Malaysia

Chandrasekharan N

Malays J Pathol, 1983 Aug;6:9-14.
PMID: 6599868
Fulltext A study of liver reserves of vitamin A in Malaysians

Chandrasekharan N

Malays J Pathol, 1981 Aug;4:43-7.
PMID: 7186602
Metastatic leiomyosarcoma of the thyroid: A rare entity

Che Jalil NA, Rama Chandran P, Samsudin AHZ, Yahya MM, Wan Abdul Rahman WF

Malays J Pathol, 2021 Apr;43(1):69-73.
PMID: 33903308

Cancer metastasis to the thyroid gland from non-thyroid sites is a rare presentation in clinical practice. The most frequent primary cancers that metastasise to the thyroid are renal cell carcinoma, followed by colorectal, lung and breast. We report a case of a 64-year-old Malay lady who presented with anterior neck swelling 4 years after an initial diagnosis of uterine leiomyosarcoma. She had undergone a hysterectomy procedure four years ago. Fine needle aspiration cytology of the thyroid mass suggested undifferentiated thyroid carcinoma. After multi-disciplinary discussion, the patient underwent thyroidectomy and the final histopathological diagnosis was metastatic leiomyosarcoma of the thyroid. The diagnosis was aided by an immunohistochemistry panel of positive myogenic markers, negative epithelial markers as well as the previous medical history of uterine leiomyosarcoma. Metastatic leiomyosarcoma of the thyroid may mimic primary undifferentiated (anaplastic) thyroid carcinoma (UTC) with a sarcomatoid pattern, medullary thyroid carcinoma (MTC) with spindle cells morphology and spindle cell tumour with thymus-like differentiation (SETTLE). Hence, a multidisciplinary approach must be practised by pathologists, surgeons and radiologists to consider metastatic lesions of the thyroid gland, especially when a previous history of cancer exists or is suspected.
Elevated serum rheumatoid factor, anti-citrullinated protein antibodies and active rheumatoid arthritis disease are not associated with chronic periodontitis

Che Rahim MJ, Wan Mohamad WM, Saddki N, Taib H, Wan Abhamid WZ, Wong KK, et al.

Malays J Pathol, 2019 Dec;41(3):267-272.
PMID: 31901911

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease of the joints with the involvement of other systems. Previous studies have demonstrated its association with chronic periodontitis (CP), a chronic inflammatory disease of tooth-supporting tissues. Positive rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) in RA patients have been found to be associated with CP. The aim of this study is to determine the prevalence of CP in RA patients, and to investigate the association of ACPA, RF status and RA disease activity with CP and non-CP RA patients.
MATERIALS AND METHODS: A comparative cross-sectional study involving 98 RA patients was conducted at Hospital Universiti Sains Malaysia, Kubang Kerian, Malaysia. Clinical oral examination was carried out to determine the CP status of RA patients. RF, ACPA and erythrocyte sedimentation rate (ESR) were measured, and the 28-joint Disease Activity Score (DAS-28) was assessed.
RESULTS: Forty-five patients (45.9%) were found to have CP (95% CI: 0.36-0.56). No significant difference was observed in the prevalence of positive RF (p=0.989) or ACPA (p=0.431) in CP and non-CP RA patients. There was also no significant association between active RA disease (DAS-28 score ≥3.2) and RF positivity in CP (p=0.927) and non-CP (p=0.431) RA patients as well as ACPA positivity in CP (p=0.780) and non-CP (p=0.611) RA patients.
CONCLUSION: In our cohort of RA patients, we did not find significant associations between elevated RF, ACPA, or active RA disease with the presence of CP. There were also no significant associations between elevated RF or ACPA with active RA disease.
Implications of continued upregulation of p16(INK4a) through the evolution from high-grade squamous intraepithelial lesion to invasive squamous carcinoma of the cervix

Cheah PL, Looi LM, Mun KS, Abdoul Rahman N, Teoh KH

Malays J Pathol, 2011 Dec;33(2):83-7.
PMID: 22299207

On integration into the host cervical keratinocyte genome, human papillomavirus (HPV) E7 protein binds pRB,releasing E2F from normally incompetent pRB-E2F complexes and allowing propagation of G1-S transition by the E2F. p16(INK4a), a tumour suppressor protein, increases in reflex response to counter this. 29 histologically re-confirmed low-grade squamous intraepithelial lesions (LSIL), 27 high-grade squamous intraepithelial lesions (HSIL) and 30 invasive cervical squamous carcinoma (SCC) were immunohistochemically stained for p16(INK4a) expression using the CINtec Histology Kit (REF 9511, mtm laboratories AG, Heidelberg, Germany) to re-affirm the notion that integration of HPV occurs predominantly in SCC and possibly HSIL and less in LSIL and normal squamous epithelium (NSqE). Implicit was also the attempt to understand the role of E2F, as indicated by p16(INK4a), in evolution of SCC from HSIL. No ethnic predilection was noted for LSIL, HSIL or SCC. Patients with SCC were significantly older by about 14-years compared with HSIL (p < 0.05) while there was no significant age difference between HSIL and LSIL. p16(INK4a) expression was significantly increased (p < 0.05) in both HSIL (88.9%) and SCC (83.3%) compared with LSIL (3.4%) and NSqE (0%); the NSqE being normal squamous epithelium noted in 17 of the LSIL, 19 HSIL and 5 SCC. From these findings there is suggestion that fundamental upstream events viz HPV integration, E7 upregulation followed by E2F activation occurs at point of transformation to HSIL and continues unrelentingly for another one to two decades before hitherto unclear factors convert a non-invasive lesion into an overtly invasive malignant counterpart. Interestingly, the occurrence of HSIL and LSIL in almost the same age group could mean that alteration from episomal to integrated form of HPV may not incur a prolonged incubation period, unlike from HSIL to SCC.
Fulltext Association of Ki67 with raised transaminases in hepatocellular carcinoma

Cheah PL, Looi LM, Nazarina AR, Mun KS, Goh KL

Malays J Pathol, 2008 Dec;30(2):103-7.
PMID: 19291919 MyJurnal

Transaminase enzymes, alanine (ALT) and aspartate transaminase (AST), have been reported to be raised and implicated to have prognostic value in hepatocellular carcinoma (HCC). Ki67, a marker of cellular proliferative activity, has also been noted to be increased in HCC. A study was conducted at the Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur to determine the possible association of proliferative activity, as determined by Ki67, with the transaminase enzymes. 31 cases of histologically diagnosed HCC who underwent tumour resection were retrieved from departmental archives. The patients' ages ranged between 40 to 79 years with a mean of 58.3 years. There was a male preponderance with M:F = 2.9:1. Ethnic Chinese formed 83.9% of the cases. 4 microm sections, cut from the formalin-fixed, paraffin-embedded tumour tissue block of each case, were immunohistochemically stained with Ki67 (DAKO monoclonal MIB-1) using the commercial DakoCytomation EnVision+System-HRP kit. The latest ALT and AST levels, assayed within 7 days prior to tumour resection, were retrieved from the patients' case records. 24 (77.4%) HCC demonstrated elevation of either ALT and/or AST. 27 (87.1%) HCC were immunopositive for Ki67. Ki67 immunoexpression was significantly correlated with raised transaminases (p<0.05). Hypothetically, the mechanism by which this phenomenon may occur may simply be release of transaminases due to destruction of hepatocytes by the cancer. Thus rising levels of the transaminases could signal a more rapid growth of the tumour and these routinely performed tests can be of prognostic value in management of HCC patients.
Detection of the human papillomavirus in cervical carcinoma: a comparison between non-isotopic in-situ hybridisation and polymerase chain reaction as methods for detection in formalin-fixed, paraffin-embedded tissues

Cheah PL, Looi LM

Malays J Pathol, 2008 Jun;30(1):37-42.
PMID: 19108410

Cervical carcinoma, the second most common malignancy in Malaysian females, is aetiologically linked to the human papillomavirus (HPV). A study was conducted at the Department of Pathology, University of Malaya Medical Centre to compare the identification of HPV 6, 11, 16 and 18 in 40 archived formalin-fixed, paraffin-embedded cervical carcinoma by non-isotopic in-situ hybridisation (NISH) and polymerase chain reaction (PCR). HPV L1 ORF consensus PCR was also carried in cases which were negative on HPV type-specific PCR. NISH detected HPV 16 in 13 (32.5%) cases with one case demonstrating a concomitant HPV 18. beta-globin DNA PCR was carried out on the same paraffin block as for NISH in 27 cases and on a different paraffin block in 13, with amplification in 9 of the former and 3 of the latter. Thus only 12 cases were subjected to further HPV PCR. HPV was detected in 10 (83.3%) with HPV 16 in 9 cases and HPV L1 ORF in one. When using the same paraffin block for both methods of HPV detection, NISH detected HPV in 6 and PCR in 7. NISH failed to detect HPV in a case detected by PCR. 2 cases were negative for HPV using both methods. Hence, HPV detection results by NISH and PCR were concordant in 88.9%. Interestingly, NISH detected HPV in 2 cases with non-amplifiable beta-globin DNA. Using an alternative paraffin block for HPV PCR from NISH, HPV DNA was detected in 3 cases, two of which also showed type-specific positivity on NISH. The third case did not reveal type-specific positivity with NISH or PCR but demonstrated HPV DNA on L1 ORF consensus PCR. It thus appears that PCR and NISH can be successfully used to detect HPV in formalin-fixed, paraffin-embedded tissue and in the presence of intact DNA NISH may be as sensitive as PCR.
Fulltext Significance of Bcl-2 and Bax proteins in cervical carcinogenesis: an immunohistochemical study in squamous cell carcinoma and squamous intraepithelial lesions

Cheah PL, Looi LM

Malays J Pathol, 2006 Jun;28(1):1-5.
PMID: 17694953 MyJurnal

Sixteen low grade (LSIL), 22 high grade (HSIL) squamous intraepithelial lesions, 28 invasive (13 stage I and 15 stage II-IV) squamous cell carcinoma (SCC) and 15 benign cervices were immunohistochemically studied for involvement of Bcl-2 and Bax proteins in cervical carcinogenesis. 4-microm sections of the cases were immunostained for Bcl-2 (Clone 124: Dako) and Bax (Dako) and staining intensity was rated as 1 (light), 2 (moderate) and 3 (strong) and percentage cellular staining as 0 (negative), 1 (1-25%), 2 (26-50%), 3 (51-75%) and 4 (>75%) with score derived by multiplying staining intensity and percentage positivity. The cut-off value, indicating upregulated expression, was computed as >2 for Bcl-2 and >8 for Bax. Bcl-2 was upregulated (p < 0.05) in HSIL and Bax in SCC when compared with benign cervical squamous epithelium. Bcl-2 expression was confined to the lower third of the epithelium in the benign cervices and LSIL. In HSIL, expression reached the middle and upper thirds. 4 (30.8%) HSIL with upregulated Bcl-2 demonstrated intensification of staining around the basement membrane. SCCs showed "diffuse" (evenly distributed) or "basal" (intensified staining around the periphery of the invading tumour nests) expression of Bcl-2. Of the 5 SCCs with upregulated Bcl-2, 1 of 2 (50%) stage I and 3 (100%) stage II-IV tumours exhibited the "basal" pattern. Benign cervical squamous epithelium, LSIL, HSIL and SCC showed a generally diffuse Bax expression. Thus, Bcl-2 and Bax appeared to be upregulated at different stages of cervical carcinogenesis, Bcl-2 in HSIL and Bax after invasion. Intensification of staining of Bcl-2 at the basement membrane in some HSIL and SCC is interesting and may augur for increased aggressiveness.

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