MyMedR

Impact of saturated and trans fatty acid enriched oil blends on atherosclerosis in rabbits fed cholesterol-free diets

Sundram K, Pathmanathan R, Wong KT, Baskaran G

Asia Pac J Clin Nutr, 1997 Mar;6(1):31-5.

Thirty six-male New Zealand White rabbits subdivided into four dietary groups (9 animals per group) were fed high fat (36% en), cholesterol-free diets for nine months. The dietary oil blends were formulated to contain high levels of the target fatty acids namely trans-rich (partially hydrogenated soybean oil; TRANS), cis monounsaturated-rich (rapeseed, sunflower seed oil and palm olein; MONO), palmitic-rich (palm olein; POL) and lauric-myristic rich (coconut, palm kernel and corn oils; LM). Ad libitum feeding of the rabbits resulted in normal growth throughout the nine months and no differences in the final body weights of the animals were evident at autopsy. Plasma total cholesterol was significantly elevated only by the LM enriched diet compared with all other treatments; values were comparable between the other three treatment groups. Changes in the total cholesterol were not reflected in the VLDL and LDL lipoproteins. However, HDL-cholesterol was significantly lowered by the TRANS diet compared with all other dietary groups. HDL-cholesterol was also significantly increased by the LM diet in comparison to the POL-diet. Both adipose and liver triglyceride fatty acid compositions tended to reflect the type of fatty acids fed the animals. Trans fatty acids were evident only in animals fed the trans diet and it was apparent that the trans fatty acids competed with linoleic acid for incorporation into these tissues. Increased concentrations of lauric and myristic fatty acids in the LM-fed animals were also evident. In the POL and high MONO fed rabbits, palmitic and oleic fatty acids (respectively) were concentrated in the adipose and liver. The diets, however, failed to induce severe atherosclerosis in this study. This can be explained, in part, by the lack of dietary cholesterol and the use of plant (rather than animal) proteins in our dietary formulations. The effect of these important atherosclerosis modulators in association with these fatty acids requires further evaluation.

Fulltext Ileal strongyloidiasis in a Malaysian patient

Shekhar KC, Pathmanathan R, Loo VS, Chan KS

Med J Malaysia, 1999 Sep;54(3):361-3.

PMID: 11045064

Fulltext Declining post-mortems: a cause for concern

Pathmanathan R, Chandrasekharan N

Med J Malaysia, 1985 Dec;40(4):267-70.

PMID: 3842725

Fulltext Detection of epidermal growth factor receptor mutations in formalin fixed paraffin embedded biopsies in Malaysian non-small cell lung cancer patients

Shi Yeen TN, Pathmanathan R, Shiran MS, Ahmad Zaid FA, Cheah YK

J Biomed Sci, 2013 Apr 16;20:22.

PMID: 23590575 DOI: 10.1186/1423-0127-20-22

BACKGROUND: Somatic mutations of the epidermal growth factor receptor (EGFR) are reportedly associated with various responses in non-small cell lung cancer (NSCLC) patients receiving the anti-EGFR agents. Detection of the mutation therefore plays an important role in therapeutic decision making. The aim of this study was to detect EGFR mutations in formalin fixed paraffin embedded (FFPE) samples using both Scorpion ARMS and high resolution melt (HRM) assay, and to compare the sensitivity of these methods.

RESULTS: All of the mutations were found in adenocarcinoma, except one that was in squamous cell carcinoma. The mutation rate was 45.7% (221/484). Complex mutations were also observed, wherein 8 tumours carried 2 mutations and 1 tumour carried 3 mutations.

CONCLUSIONS: Both methods detected EGFR mutations in FFPE samples. HRM assays gave more EGFR positive results compared to Scorpion ARMS.

ERG oncoprotein expression in prostate carcinoma patients of different ethnicities

Kelly GM, Kong YH, Dobi A, Srivastava S, Sesterhenn IA, Pathmanathan R, et al.

Molecular and clinical oncology, 2015 Jan;3(1):23-30.

PMID: 25469265

Overexpression of the erythroblast transformation-specific-related gene (ERG) oncoprotein due to transmembrane protease, serine 2 (TMPRSS2)-ERG fusion, the most prevalent genomic alteration in prostate cancer (CaP), is more frequently observed among Caucasian patients compared to patients of African or Asian descent. To the best of our knowledge, this is the first study to investigate the prevalence of ERG alterations in a multiethnic cohort of CaP patients. A total of 191 formalin-fixed paraffin-embedded sections of transrectal ultrasound-guided prostate biopsy specimens, collected from 120 patients treated at the Sime Darby Medical Centre, Subang Jaya, Malaysia, were analyzed for ERG protein expression by immunohistochemistry using the anti-ERG monoclonal antibody 9FY as a surrogate for the detection of ERG fusion events. The overall frequency of ERG protein expression in the population evaluated in this study was 39.2%. Although seemingly similar to rates reported in other Asian communities, the expression of ERG was distinct amongst different ethnic groups (P=0.004). Malaysian Indian (MI) patients exhibited exceedingly high expression of ERG in their tumors, almost doubling that of Malaysian Chinese (MC) patients, whereas ERG expression was very low amongst Malay patients (12.5%). When collectively analyzing data, we observed a significant correlation between younger patients and higher ERG expression (P=0.04). The prevalence of ERG expression was significantly different amongst CaP patients of different ethnicities. The higher number of ERG-expressing tumors among MI patients suggested that the TMPRSS2-ERG fusion may be particularly important in the pathogenesis of CaP amongst this group of patients. Furthermore, the more frequent expression of ERG among the younger patients analyzed suggested an involvement of ERG in the early onset of CaP. The results of this study underline the value of using ERG status to better understand the differences in the etiology of CaP initiation and progression between ethnic groups.

Fulltext Gastric strongyloidiasis in a Malaysian patient

Shekhar KC, Krishnan R, Pathmanathan R, Fook CS

Southeast Asian J. Trop. Med. Public Health, 1997 Mar;28(1):158-60.

PMID: 9322300

Strongyloides stercoralis infection is of low prevalence in Malaysia. We report an unusual case presenting primarily with gastric symptoms. The patient was a 72 years old Chinese male admitted for progressive weight loss and abdominal bloating. Gastroscopic examination revealed mucosal prepyloric elevations in the gastric mucosa. Gastric strongyloidiasis was confirmed by the presence of adult forms, as well as ova and larval rhabditiform stages of the worm in the gastric mucosal crypts. We believe that this is the first histologically documented case of gastric strongyloidiasis in Malaysia.

Gene expression in human oral squamous cell carcinoma is influenced by risk factor exposure

Cheong SC, Chandramouli GV, Saleh A, Zain RB, Lau SH, Sivakumaren S, et al.

Oral Oncol, 2009 Aug;45(8):712-9.

PMID: 19147396 DOI: 10.1016/j.oraloncology.2008.11.002

Oral squamous cell carcinoma (OSCC) is a world health problem and is associated with exposure to different risk factors. In the west, smoking and alcohol consumption are considered to be the main risk factors whilst in India and southeast Asia, betel quid (BQ) chewing is predominant. In this study, we compared the gene expression patterns of oral cancers associated with BQ chewing to those caused by smoking using Affymetrix microarrays. We found that 281 genes were differentially expressed between OSCC and normal oral mucosa regardless of aetiological factors including MMP1, PLAU, MAGE-D4, GNA12, IFITM3 and NMU. Further, we identified 168 genes that were differentially expressed between the BQ and smoking groups including CXCL-9, TMPRSS2, CA12 and RNF24. The expression of these genes was validated using qPCR using independent tissue samples. The results demonstrate that whilst common genes/pathways contribute to the development of oral cancer, there are also other gene expression changes that are specific to certain risk factors. The findings suggest that different carcinogens activate or inhibit specific pathways during cancer development and progression. These unique gene expression profiles should be taken into consideration when developing biomarkers for future use in prognostic or therapeutic applications.

Light microscopic and three-dimensional morphology of the human muscular sarcocyst

Wong KT, Clarke G, Pathmanathan R, Hamilton PW

Parasitol Res, 1994;80(2):138-40.

PMID: 8202453

Established criteria for morphological typing of sarcocysts was applied to a large series of cases of human skeletal muscle sarcocystosis in Malaysia to determine the type of sarcocyst present. We also wanted to test the general usefulness of this classification and to determine if there are any new cyst types. Three-dimensional (3-D) reconstruction was done to see if the sarcocyst has a distinct 3-D morphology. A total of 66 sarcocysts from 21 cases of human muscle sarcocystosis obtained from a previous prevalence study were examined. Tissue sections (5 microns thick) were stained with haematoxylin and eosin and studied under the light microscope. For 3-D reconstruction, an image analyser was used to align and reconstruct the sarcocyst after microscopic images had been captured with a charge-coupled device (CCD) camera. All the cysts best fit into the type 4 category. This classification is generally useful, although cyst wall characteristics and zoite size appear to be the most reliable criteria for classification. The cyst width averaged 77 microns (range, 30-137.5 microns). Cyst walls were smooth, had no cytophaneres and were less than 1 micron thick. No secondary cyst wall or surrounding inflammation was evident. Numerous cyst merozoites with diameters averaging 1 micron filled the cyst lumen. Although septa were not apparent, in many cysts, zoites were arranged in a unique, curvilinear fashion that suggested their presence. 3-D reconstruction showed the sarcocyst to be a long, tortuous "cylinder" with no branching or other distinguishing feature.

Retroperitoneal malignant fibrous histiocytoma causing profuse bleeding per rectum

Sim PH, Pathmanathan R, Jalleh RP

Aust N Z J Surg, 1995 Jan;65(1):68-70.

PMID: 7818432

A case is reported of retroperitoneal malignant fibrous histiocytoma (MFH) invading into the colon, causing fresh bleeding per rectum. It illustrates the difficulty encountered in the pre-operative diagnosis of this condition, especially in a patient with an atypical presentation of profuse lower gastrointestinal bleeding.

Fulltext Retroperitoneal malignant fibrous histiocytoma with renal involvement

Sim PH, Razack AH, Pathmanathan R, Jalleh RP

Med J Malaysia, 1995 Jun;50(2):189-91.

PMID: 7565195

Malignant fibrous histiocytoma is a mesenchymal tumour which can involve the genitourinary organs primarily or by secondary extension. Both conditions are rare. We report four cases of retroperitoneal malignant fibrous histiocytoma involving the kidney by local extension. Diagnosis was difficult because of diverse, non-specific clinical features and may only be reached at operation or post mortem. Prognosis is poor. Although en bloc tumour resection with nephrectomy was possible in two patients, they returned with recurrences.

Three cases of human Sarcocystis infection with a review of human muscular sarcocystosis in Malaysia

Pathmanathan R, Kan SP

Trop Geogr Med, 1992 Jan;44(1-2):102-8.

PMID: 1496700

Three cases of muscular sarcocystosis from West Malaysia are reported. The morphological features of the parasites from these three cases are similar to the eight cases previously reported from this country. A review of this total of eleven cases of muscular sarcocystosis showed that they were all incidental findings, where man acted as intermediate hosts of as yet unknown Sarcocystis spp. These cases of muscular sarcocystosis were probably zoonotic in origin and associated with close contact with definitive hosts (both domestic and wild animals) thus permitting the contamination of food and drink with sporocysts shed by these definitive hosts. These infections were probably acquired locally as most of the subjects were born in Malaysia and none had ever left the country to stay elsewhere. Eight of the eleven cases reported were associated with malignancies, especially of the tongue and nasopharynx.

Fulltext Two cases of human sarcocystosis in East Malaysia

Pathmanathan R, Kan SP

Med J Malaysia, 1987 Sep;42(3):212-4.

PMID: 3147362

The first two cases of human muscular sarcocystosis are reported from East Malaysia, in Sabalt and Sarawak respectively. Sarcocysts were seen iin biopsied specimen from the nasopharynx of both patients who had carcinoma of the nasopharynx. The measurements and appearances of the cysts and the zoites within the cysts were compared with the human cases of sarcocystosis previously reported in West Malaysia. Zoonotic and other aspects of these cases of East Malaysian sarcocystosis are discussed.

Hepatotoxicity of amiodarone

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.

Primary cardiac amyloidosis

Jeyamalar R, Pathmanathan R, Yap SF, Kannan P

Ann Acad Med Singap, 1991 Nov;20(6):795-7.

PMID: 1803972

Cardiac amyloidosis is an uncommon and often unrecognised cause of cardiac failure. It is an infiltrative disease that may mimic either a restrictive or hypertrophic cardiomyopathy, constrictive pericarditis, coronary artery disease or valvular heart disease. The diagnosis should be suspected in a patient with cardiac failure who has low voltage complexes on the electrocardiogram, in association with increased myocardial mass and echogenicity on the echocardiogram. The definitive diagnosis, however, can only be made by endomyocardial biopsy or biopsy of any involved organ in systemic amyloidosis. Prognosis is poor and treatment ineffective.

Cystic lesion of the parotid gland with squamous metaplasia mistaken for squamous cell carcinoma. A case report

Jayaram G, Pathmanathan R, Khanijow V

Acta Cytol., 1998 Nov-Dec;42(6):1468-72.

PMID: 9850664

BACKGROUND: The diverse range of diseases that affect the salivary glands may lead to problems and pitfalls in cyto-diagnosis. While false negative diagnosis of cystic salivary gland tumors is well known, false positive cytodiagnosis in nonneoplastic salivary cysts is less well documented.

CASE: An 85-year-old female presented with a painless left parotid gland swelling of three months' duration. Fine needle aspiration cytology yielded fluid, smears of which showed keratinizing squamous cells with nuclear atypia leading to a cytologic diagnosis of cystic squamous cell carcinoma. A total radical parotidectomy followed. Histopathologic study showed cystic dilatation of many of the salivary ducts, which were lined with metaplastic squamous epithelium that showed atypia. There was no evidence of squamous cell carcinoma.

CONCLUSION: Squamous metaplasia is known to occur in benign salivary gland lesions, such as pleomorphic adenoma and Warthin's tumors, as well as in salivary duct cysts and necrotizing sialometaplasia. However, atypical squamous metaplasia of salivary duct cysts mimicking squamous cell carcinoma on cytology is unusual.

Human infection with Dirofilaria repens in Malaysia

Shekhar KC, Pathmanathan R, Krishnan R

J Helminthol, 1996 Sep;70(3):249-52.

PMID: 8960220

Human dirofilariasis is a rare infection in Malaysia. Thus far, only two human cases have been reported viz. Dirofilaria immitis and D. (Nochtiella) repens and in both instances, adult worms were recovered from infected patients. The two cases reported in the present study, one from Melaka and the other from Penang, were diagnosed histologically. Based on the diagnostic criteria for identifying Dirofilaria in tissue sections, the parasites were identified as D. (Nochtiella) repens.

Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications

McCart Reed AE, Kalaw E, Nones K, Bettington M, Lim M, Bennett J, et al.

J Pathol, 2019 02;247(2):214-227.

PMID: 30350370 DOI: 10.1002/path.5184

Metaplastic breast carcinoma (MBC) is relatively rare but accounts for a significant proportion of global breast cancer mortality. This group is extremely heterogeneous and by definition exhibits metaplastic change to squamous and/or mesenchymal elements, including spindle, squamous, chondroid, osseous, and rhabdomyoid features. Clinically, patients are more likely to present with large primary tumours (higher stage), distant metastases, and overall, have shorter 5-year survival compared to invasive carcinomas of no special type. The current World Health Organisation (WHO) diagnostic classification for this cancer type is based purely on morphology - the biological basis and clinical relevance of its seven sub-categories are currently unclear. By establishing the Asia-Pacific MBC (AP-MBC) Consortium, we amassed a large series of MBCs (n = 347) and analysed the mutation profile of a subset, expression of 14 breast cancer biomarkers, and clinicopathological correlates, contextualising our findings within the WHO guidelines. The most significant indicators of poor prognosis were large tumour size (T3; p = 0.004), loss of cytokeratin expression (lack of staining with pan-cytokeratin AE1/3 antibody; p = 0.007), EGFR overexpression (p = 0.01), and for 'mixed' MBC, the presence of more than three distinct morphological entities (p = 0.007). Conversely, fewer morphological components and EGFR negativity were favourable indicators. Exome sequencing of 30 cases confirmed enrichment of TP53 and PTEN mutations, and intriguingly, concurrent mutations of TP53, PTEN, and PIK3CA. Mutations in neurofibromatosis-1 (NF1) were also overrepresented [16.7% MBCs compared to ∼5% of breast cancers overall; enrichment p = 0.028; mutation significance p = 0.006 (OncodriveFM)], consistent with published case reports implicating germline NF1 mutations in MBC risk. Taken together, we propose a practically minor but clinically significant modification to the guidelines: all WHO_1 mixed-type tumours should have the number of morphologies present recorded, as a mechanism for refining prognosis, and that EGFR and pan-cytokeratin expression are important prognostic markers. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Fulltext Metaplastic breast cancers frequently express immune checkpoint markers FOXP3 and PD-L1

Kalaw E, Lim M, Kutasovic JR, Sokolova A, Taege L, Johnstone K, et al.

Br J Cancer, 2020 11;123(11):1665-1672.

PMID: 32939056 DOI: 10.1038/s41416-020-01065-3

BACKGROUND: Metaplastic breast carcinoma encompasses a heterogeneous group of tumours with differentiation into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements. Emerging immunotherapies targeting Programmed Death Ligand 1 (PD-L1) and immune-suppressing T cells (Tregs) may benefit metaplastic breast cancer patients, which are typically chemo-resistant and do not express hormone therapy targets.

METHODS: We evaluated the immunohistochemical expression of PD-L1 and FOXP3, and the extent of tumour infiltrating lymphocytes (TILs) in a large cohort of metaplastic breast cancers, with survival data.

RESULTS: Metaplastic breast cancers were significantly enriched for PD-L1 positive tumour cells, compared to triple-negative ductal breast cancers (P

Anorectal melanoma

Jalleh RP, Pathmanathan R, Krishnan MM, Mukherjee A

Postgrad Med J, 1988 Sep;64(755):669-71.

PMID: 3251217

Four cases of anorectal melanoma are presented. The authors believe that this is the first report of the occurrence of this tumour in Malays. Advanced disease at initial presentation accounts for the poor prognosis observed in this series. Surgery remains the principal treatment modality, although controversy exists regarding optimal extent of resection.

Metastatic endodermal sinus tumor of cerebellum and brainstem

Sinniah D, Chee CP, Pathmanathan R, Nuruddin R

Med. Pediatr. Oncol., 1988;16(1):57-61.

PMID: 3340064

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