Oral histoplasmosis in Malaysia: A retrospective analysis of cases reported in Stomatology Unit, Institute for Medical Research during 1995-2016.

Histoplasmosis is a systemic fungal infection caused by inhalation of Histoplasma capsulatum, which is mainly found in bird and bat droppings. Oral manifestation of histoplasmosis may be the only initial manifestation of the disease or associated with chronic disseminated histoplasmosis. The first review of oral histoplasmosis among Malaysian population from 1967 to 1994 (27 years) revealed the occurrence of 37 cases, reported by Ng and Siar in 1996. This current study is the updated overview of oral histoplasmosis cases in Malaysia. The objective of the study was to review and describe clinical and demographic profile of oral histoplasmosis in Malaysia and to correlate histopathological features of oral histoplasmosis with patient's immunity status. We reviewed oral histoplasmosis cases diagnosed in Stomatology Unit, Institute for Medical Research (IMR), Kuala Lumpur from 1995 until 2016. The data was retrieved from the Oral Pathology Information system (OPIS) Stomatology Unit, IMR, which is the largest oral pathology database in Malaysia. Information regarding patients' sociodemographic data, medical illness, clinical presentation, histopathological features, and referring healthcare institutions was extracted from the clinical information which accompanied the biopsy request form. A total of 39 cases of oral histoplasmosis were identified from 1995-2016. Majority of them were male (89.7%). The age ranges from 29 to 85 years with mean age of 57.8 years. Almost half of them were Malays (51.3%), followed by Chinese (33.3%), Indians (7.7%), and other races (7.7%). The most common sites of oral histoplasmosis were tongue, gingiva, palate, and alveolar ridge. The main clinical presentation was ulcer (61.5%) whereas 38.5% presented clinically as swelling. 17.9% of patients were seropositive for human immunodeficiency virus (HIV), 12.8% had tuberculosis, 10.3% had diabetes mellitus, and 2.6% with hepatitis C. The incidence of oral histoplasmosis should raise suspicion of hidden immunodepression and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). Early recognition and diagnosis is crucial to reduce risk of morbidity and mortality.

Oral histoplasmosis in Malaysia: A retrospective analysis of cases reported in Stomatology Unit, Institute for Medical Research during 1995-2016

@#Histoplasmosis is a systemic fungal infection caused by inhalation of Histoplasma capsulatum, which is mainly found in bird and bat droppings. Oral manifestation of histoplasmosis may be the only initial manifestation of the disease or associated with chronic disseminated histoplasmosis. The first review of oral histoplasmosis among Malaysian population from 1967 to 1994 (27 years) revealed the occurrence of 37 cases, reported by Ng and Siar in 1996. This current study is the updated overview of oral histoplasmosis cases in Malaysia. The objective of the study was to review and describe clinical and demographic profile of oral histoplasmosis in Malaysia and to correlate histopathological features of oral histoplasmosis with patient’s immunity status. We reviewed oral histoplasmosis cases diagnosed in Stomatology Unit, Institute for Medical Research (IMR), Kuala Lumpur from 1995 until 2016. The data was retrieved from the Oral Pathology Information system (OPIS) Stomatology Unit, IMR, which is the largest oral pathology database in Malaysia. Information regarding patients’ sociodemographic data, medical illness, clinical presentation, histopathological features, and referring healthcare institutions was extracted from the clinical information which accompanied the biopsy request form. A total of 39 cases of oral histoplasmosis were identified from 1995-2016. Majority of them were male (89.7%). The age ranges from 29 to 85 years with mean age of 57.8 years. Almost half of them were Malays (51.3%), followed by Chinese (33.3%), Indians (7.7%), and other races (7.7%). The most common sites of oral histoplasmosis were tongue, gingiva, palate, and alveolar ridge. The main clinical presentation was ulcer (61.5%) whereas 38.5% presented clinically as swelling. 17.9% of patients were seropositive for human immunodeficiency virus (HIV), 12.8% had tuberculosis, 10.3% had diabetes mellitus, and 2.6% with hepatitis C. The incidence of oral histoplasmosis should raise suspicion of hidden immunodepression and may be the first manifestation of acquired immunodeficiency syndrome (AIDS). Early recognition and diagnosis is crucial to reduce risk of morbidity and mortality.

An observational study of trigeminal neuralgia patients taking carbamazepine during the fasting month of Ramadan.

INTRODUCTION: Trigeminal neuralgia is an agonising orofacial pain affecting unilaterally the distribution of the trigeminal nerve and it usually occurs in the middle and older age groups. Carbamazepine which is an anti-neuralgic as well as an anti-convulsant medication is the first line drug for treatment of trigeminal neuralgia. It is commonly taken as one tablet (200 mg) three times a day. MATERIALS AND METHODS: This is an observational study carried out from April to September 2014 to determine how Muslim patients on carbamazepine treatment for trigeminal neuralgia cope with their neuralgic pain. The pattern of how the medication was taken during the fasting month of Ramadan was also observed. RESULTS: A total of 29 patients participated in this study and 27(93%) observed the fast. Ten of them adjusted the carbamazepine dose from three times pre-Ramadan to twice daily during the fasting month. Three patients continued fasting despite feeling the pain during the daytime while five patients had their pain under control with the newly adjusted dose. CONCLUSION: Medical professionals should advise trigeminal neuralgia patients on how to take and adjust their carbamazepine dose during the fasting month.

Mineral density volume gradients in normal and diseased human tissues.

Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095 mg/cc, bone: 570-1415 mg/cc, cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc, hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770 mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

Thoracic response to shoulder belt loading: comparison of tabletop and frontal sled tests with PMHS.

OBJECTIVE: The recent refinement of high-rate optical tracking allows dramatically detailed thoracic deformation measurements to be taken during postmortem human subject (PMHS) sled tests. These data allow analysis of restraint belt geometry and the 3-dimensional thoracic deformations generated by belt impingement. One consequence of this new capability is a better understanding of complementary thoracic characterization experiments such as tabletop tests and how the thoracic response can be interpreted for applications involving more complex loading mechanisms. METHODS: This article reports a detailed evaluation of the timing, magnitude, and direction of the applied belt forces and the resulting thoracic deformations in 2 previously performed tests series involving frontal sled tests and tabletop belt-loading tests. RESULTS: In the sled tests, the posteriorly directed component (SAE x) of the belt tension (F(B)) was F(Bx) = 0.70 F(B) at the shoulder but only F(Bx) = 0.14 F(B) where the belt engaged the anterolateral torso inferiorly. The corresponding components on the tabletop were F(Bx) = 0.60 F(B) (shoulder) and F(Bx) = 0.48 F(B) (lower). CONCLUSIONS: When these components are cross-plotted with chest deflection, pronounced consequences of thoracic anterior wall deformation patterns due to flexion of the thoracic spine and the internal viscera's inertia can be seen in the effective thoracic stiffness. Supplemental materials are available for this article. Go to the publisher's online edition of Traffic Injury Prevention to view the supplemental file.

Duplication of lower lip and mandible--a rare diprosopus.

Diprosopus or duplication of the lower lip and mandible is a very rare congenital anomaly. We report this unusual case occurring in a girl who presented to our hospital at the age of 4 months. Surgery and problems related to this anomaly are discussed.

Comparison of Hybrid III child test dummies to pediatric PMHS in blunt thoracic impact response.

The limited availability of pediatric biomechanical impact response data presents a significant challenge to the development of child dummies. In the absence of these data, the development of the current generation of child dummies has been driven by scaling of the biomechanical response requirements of the existing adult test dummies. Recently published pediatric blunt thoracic impact response data provide a unique opportunity to evaluate the efficacy of these scaling methodologies. However, the published data include several processing anomalies and nonphysical features. These features are corrected by minimizing instrumentation and processing error to improve the fidelity of the individual force-deflection responses. Using these data, biomechanical impact response corridors are calculated for a 3-year-old child and a 6-year-old child. These calculated corridors differ from both the originally published postmortem human subject (PMHS) corridors and the impact response requirements of the current child dummies. Furthermore, the response of the Hybrid III 3-year-old test dummy in the same impact condition shows a similar deflection but a significantly higher force than the 3-year-old corridor. The response of the Hybrid III 6-year-old dummy, on the other hand, correlates well with the calculated 6-year-old corridor. The newly developed 3-year-old and 6-year-old blunt thoracic impact response corridors can be used to define data-driven impact response requirements as an alternative to scaling-driven requirements.

A retrospective clinicopathological study of 59 osteogenic sarcoma of jaw bone archived in a stomatology unit.

OBJECTIVES: To determine the clinicopathological features of osteogenic sarcomas of the mandible and maxilla. MATERIALS AND METHODS: A retrospective study was carried out on all osteosarcoma from the jaw diagnosed in the Stomatology Unit, Institute for Medical Research, Kuala Lumpur from 1967 to 2008. All data regarding the age at presentation, gender, race, clinical presentation, radiographical findings and diagnoses were retrieved from computerized records. RESULTS: There were 59 cases (36 males and 23 females) with ages ranging from 7 to 68 years. The patients comprised 28 Malays, 16 Chinese, 2 Indians and 13 of other ethnicity. Forty cases involved the mandible and 19 the maxilla. The main complaint was painless or painful bony swelling. Nine cases presented with numbness of the associated region. Four patients had history of prior radiotherapy. The radiographic findings which varied from radiolucent to radiopaque lesions were mentioned in only 26 cases. Histologically, the majority (30) were osteoblastic, 19 chondroblastic, 6 fibroblastic and 4 telangiectatic in type. No small cell type osteosarcoma was identified. CONCLUSION: Osteogenic sarcoma of the jaws is a rare malignant bone tumour. Over 40 years, there were only 59 cases diagnosed by our institution and to date this is the first report of jaw osteosarcoma in Malaysia.

Overexpression of clusterin correlates with tumor progression, metastasis in gastric cancer: a study on tissue microarrays.

Clusterin (CLU) is expressed in a wide variety of human tissues and fluids. Overexpression of cytoplasmic clusterin (sCLU) has been implicated in cancer development and progression. The aim of the present study is to evaluate the association of sCLU overexpression with clinicopathological features of human gastric carcinomas (GC).We constructed a gastric cancer tissue microarray containing 173 primary gastric carcinomas and 70 paired non-neoplastic mucosa specimens. The expression of sCLU was studied by immunohistochemistry. The correlations between sCLU expression and clinicopathological features, p53 abnormality, as well as Ki67 activation were analyzed. Overexpressions of sCLU was detected in 28.5% (n=165) of primary GCs by immunohistochemical staining, but not in non-neoplastic mucosa. Clinical association study found that overexpression of sCLU was significantly correlated with lymph-node metastasis (p < 0.001), tumor invasion (p < 0.001) and TNM stage (p < 0.001). In Kaplan-Meier survival analysis, overexpression of sCLU was significantly correlated with unfavorable survival in advanced GCs (p < 0.03). Furthermore, the association of sCLU with abnormal expression of p53 was ascertained. These results suggested that overexpression of sCLU was involved in the progression of GC and it's oncogenic function might be associated with p53 abnormality. Overexpression of sCLU seems to be related with patient's shorter survival in late stage GC.

Rapid identification of uropathogenic Escherichia coli of the O25:H4-ST131 clonal lineage using the DiversiLab repetitive sequence-based PCR system.

Several recent studies have highlighted the emergence of a globally disseminated clone of uropathogenic and invasive Escherichia coli isolates of serotype O25:H4 and sequence type 131. The ability to characterize rapidly E. coli isolates of this lineage would facilitate enhanced surveillance for this pathogen. We have used the semi-automated DiversiLab repetitive PCR-based system to analyse a collection of 35 clinical isolates of uropathogenic E. coli from across the UK, with particular focus on the O25:H4-ST131 lineage. All isolates had been characterized using multilocus sequence typing (MLST), and 14 had previously been typed using pulsed-field gel electrophoresis (PFGE). The DiversiLab system allowed discrimination of O25:H4-ST131 isolates from those of other E. coli lineages. It was slightly more discriminatory than MLST, but was less discriminatory than PFGE. With an analysis time of <4 h between receipt of a cultured organism and provision of a typing result, the system offers information on a real-time basis, a major advantage over current practice. We suggest that introduction of the DiversiLab system would be useful for rapid exclusion of E. coli isolates during outbreak investigations, and that the approach could be employed for surveillance for pathogenic or antibiotic-resistant clones of this organism.

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

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.

The use of immunohistochemistry in an oral pathology laboratory.

Immunohistochemistry has become part of normal routine diagnostic work in the Stomatology Unit, Institute for Medical Research, Kuala Lumpur. Of 9523 cases received from the year 2000 to 2005, 197 cases (2.1%) required immunohistochemical staining. These cases ranged from benign to malignant lesions. They include lymphomas (n=41), epithelial tumours (n=29), neural lesions (n=21), fibroblastic/myofibroblastic tumours (n=16), small round cell tumour (n=11), vascular tumours (n=4), smooth muscle tumours (n=4), myxomatous tumours (n=4) and skeletal muscle tumours (n=1). In most of the cases (69.5%), immunohistochemical staining was mandatory to reach a definite diagnosis, while 60 cases (30.5%) required immunohistochemistry in confirming the diagnosis. In 32 cases (16.2%), definitive diagnosis could not be made due to the small size of the specimens received or the results of immunohistochemistry were inconclusive. Standardization of techniques, competent medical laboratory technologists and sufficient budget allocation are important in producing a high quality immunohistochemistry service.

Diversity of gammadelta T cells in patients with Behcet's disease is indicative of polyclonal activation.

OBJECTIVE: Behcet's disease (BD) is a multisystemic disease, with vasculitic lesions in the oral and genital mucosa, eyes, joints, skin and brain. We have previously found that gammadelta T cells are increased in peripheral blood of BD patients. The aim of this study was to investigate the extent of gammadelta T cells in oral biopsies from BD patients with special emphasis on the restriction of Vgamma and Vdelta usage. PATIENTS AND METHODS: Expression of Vgamma and Vdelta chains on peripheral blood gammadelta T cells from 31 BD patients and 19 healthy controls was analysed by flow cytometry and the expression of Vgamma and Vdelta chains in nine ulcerated and eight non-ulcerated oral mucosa from BD patients and non-ulcerated oral mucosa from three healthy controls was analysed by immunohistochemistry. RESULTS: Vgamma9 and Vdelta2 were the predominant chains expressed in peripheral blood of BD patients, although other Vgamma and Vdelta chains were also expressed. The presence of gammadelta T cells was only observed in the ulcerated oral mucosa but not in the non-ulcerated mucosa from the BD patients, and not in the non-ulcerated mucosa from the healthy controls. These gammadelta T cells showed no preferential expression of any of the Vgamma or Vdelta chains. CONCLUSION: These data suggest a polyclonal rather than oligoclonal activation of the gammadelta T cells. This may indicate that during repeated inflammation of the oral mucosa, the gammadelta T cells are responding to a wide variety of antigenic stimuli with consequent expansion of gammadelta T cells expressing various Vgamma and Vdelta chains and that different antigenic stimuli or responses may be responsible for the clinical heterogeneity of the disease.

Clusterin plays an important role in hepatocellular carcinoma metastasis.

To identify genes associated with tumor metastasis in hepatocellular carcinoma (HCC), gene expression profiles between a pair of primary HCC (H2-P) and their matched metastatic HCC (H2-M) were compared. Overexpression of clusterin (CLU) was found in H2-M cells. To determine the roles CLU played in HCC metastasis, CLU was transfected into H2-P cells. Overexpression of CLU in H2-P cells increased cell migration by twofold in vitro and formation of metastatic tumor nodules in liver by eightfold in vivo. To evaluate the correlation of CLU expression with HCC metastasis, the expression levels of CLU in HCCs were investigated using a tissue microarray (TMA) containing 104 pairs of primary HCCs and their matched metastases. The frequency of CLU overexpression increased significantly in metastatic HCCs (59.1%) compared with that in primary tumors (32.6%, P<0.001). To gain additional insight into the function of CLU, the expression profile of H2P-CLU was compared with vector-transfected H2-P cells by cDNA microarray. A total of 35 upregulated and 14 downregulated genes were detected in H2P-CLU. One of the upregulated genes known as YKL-40, which is implicated in matrix-remodeling and metastasis, was further studied using TMA. A significant correlation (P<0.001) between the expression levels of YKL-40 and CLU was observed, implying that the CLU-YKL-40 pathway may play an important role in HCC metastasis.

Clinico-pathological conference 2002.

INTRODUCTION: Six cases are reported, each presented at the 11th Biennial Congress of the International Association of Oral Pathologists as an instructive case for differential diagnosis on the basis of clinical, imaging or histological features. CLINICAL PICTURE: Case diagnoses included a large, possibly intraosseous, myofibroma presenting with an oral mass; Langerhans cell histiocytosis with facial skin lesions; an intraosseous vascular hamartoma of the maxilla with worrying radiological features; an unusual mixed radiolucency of the jaw caused by cemento-ossifying fibroma; an osteosarcoma of the posterior mandible causing a well-defined radiolucency and an intraoral squamous cell carcinoma in a child.

Occurrence of hepatitis E virus IgM, low avidity IgG serum antibodies, and viremia in sporadic cases of non-A, -B, and -C acute hepatitis.

Serum samples were taken from 57 patients with sporadic non-A, -B, and -C (Non A, B, C) acute hepatitis at different times after onset of the disease and tested for the presence of the hepatitis E virus (HEV) RNA, IgM, and low avidity IgG antibodies. The viral antibodies were detected using two ELISA. One assay (GL) was produced using a mixture of recombinant peptides specified by ORF2 and ORF3 of the viral genome. The other was produced with an ORF2 specified peptide, pE2. The latter occurs naturally as homodimer, it is recognized strongly in its dimeric form by human sera and, in the primate model, it confers protection against experimental HEV infection. Nineteen samples were positive for one or more of these acute markers of HEV infection, 14 of which were acute sera with elevated ALT levels and 5 were convalescent sera with normal ALT level. The results showed that icteric phase of sporadic hepatitis lasts for about 17 days and it coincides with a period when viremia is subsiding as HEV antibodies are developing. Viremia was intermittent and all but one of the 5 instances were confined to the icteric phase with elevated ALT levels. On two of these occasions, viremia preceded detection of HEV antibody, on another 2 occasions it was concurrent with the detection of pE2 specific IgM and/or low avidity IgG and only in one case of protracted viremia was the viral genome detected concurrently with avid pE2 IgG antibody. Ten (71%) of the 14 acute sera were reactive for pE2 IgM, eight (57%) were reactive for low avidity pE2 IgG, and six (43%) for the GL IgM. The sensitivity for the diagnosis of acute hepatitis E may be increased to 87% by combining pE2 IgM and viremia. GL IgM was detected later, but persisted for a longer period of time than the pE2 antibodies, and it was the only acute antibody detected in the convalescent sera.

Conformational antigenic determinants generated by interactions between a bacterially expressed recombinant peptide of the hepatitis E virus structural protein.

A 23 kDa peptide locating to amino acid residues 394 to 604 of the major Hepatitis E Virus (HEV) structural protein was expressed in E. coli. This peptide was found to interact naturally with one another to form homodimers and it was recognized strongly and commonly in its dimeric form by HEV reactive human sera. The antigenic activity associated with the dimeric form was abrogated when the dimer was dissociated into monomer and the activity was reconstituted after the monomer was re-associated into dimer again. The dimeric form of the peptide elicited a vigorous antibody response in experimental animals and the resulting antisera were found to cross-react against HEV, effecting an efficient immune capture of the virus. These results attributed the antigenic activity associated with the dimeric form of the peptide to conformational antigenic determinants generated as a result of interaction between the peptide molecules. It is suggested that some of these antigenic determinants may be expressed by the HEV capsid and raised the possibility of this bacterially expressed peptide as an HEV vaccine candidate.