Potential application of immunotherapy for modulation of pulp inflammation: opportunities for vital pulp treatment.

Caries results in the demineralization and destruction of enamel and dentine, and as the disease progresses, irreversible pulpitis can occur. Vital pulp therapy (VPT) is directed towards pulp preservation and the prevention of the progression of inflammation. The outcomes of VPT are not always predictable, and there is often a poor correlation between clinical signs and symptoms, and the events occurring at a molecular level. The inflamed pulp expresses increased levels of cytokines, including tumour necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1ß, IL-4, IL-6, IL-8, IL-17 and IL-23, which recruit and drive a complex cellular immune response. Chronic inflammation and sustained cytokine release can result in irreversible pulp damage and a decreased capacity for tissue healing. Other chronic inflammatory diseases, such as psoriasis, inflammatory bowel diseases and rheumatoid arthritis, are also characterized by an dysregulated immune response composed of relatively high cytokine levels and increased numbers of immune cells along with microbial and hard-soft tissue destructive pathologies. Whilst anti-cytokine therapies have been successfully applied in the treatment of these diseases, this approach is yet to be attempted in cases of pulp inflammation. This review therefore focuses on the similarities in the aetiology between chronic inflammatory diseases and pulpitis, and explores how anti-cytokine therapies could be applied to manage an inflamed pulp and facilitate healing. Further proof-of-concept studies and clinical trials are justified to determine the effectiveness of these treatments to enable more predictable outcomes in VPT.

Human papillomavirus and oral and oropharyngeal carcinoma: the essentials.

There is a global increase in the prevalence of human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) in Australia and New Zealand. Risk factors for HPV-positive OPSCC are male gender, white race, age older than 40 but younger than 59 years old, having multiple lifetime sex partners, having oro-genital and oro-anal sex. High-risk HPV subtypes play a major role in the pathogenesis of OPSCC, however, they play a much lesser role in oral squamous cell carcinoma (OSCC). Among the laboratory tests used to detect oncogenic HPV infection, polymerase chain reaction is a sensitive method but does not reflect the role of HPV in oncogenesis. While widely used, p16 immunohistochemistry is both a sensitive and a specific surrogate marker for oncogenic HPV infection in OPSCC, but not in OSCC. However, it is a useful prognostic marker in OPSCC. The current gold standard to accurately detect oncogenic HPV infection is E6/E7 mRNAin situ hybridization. Because both HPV-positive and p16-positive OPSCC have better short-term prognoses there is current debate and trials on treatment de-escalation in HPV-positive OPSCC. Dental practitioners can play an important role in early diagnosis of HPV-positive OPSCC.

Upregulation of angiogenesis in oral lichen planus.

OBJECTIVES: As angiogenesis is fundamental to the pathogenesis of many chronic inflammatory disorders, this study investigated the expression of various vascular markers in oral lichen planus and non-specific oral mucosal inflammatory tissues. METHODS: Archival specimens of oral lichen planus (n = 15) and inflamed tissues (n = 13) were stained using immunohistochemistry with antibodies to CD34, vascular endothelial growth factor, vascular endothelial growth factor receptor and vasohibin. Nine representative sites at the epithelial-connective tissue junction and through the fibrous connective tissue were selected, and automated analysis techniques were used to determine the extent of positivity expressed as the percentage of positive cells. Significance was denoted when P < .05. RESULTS: The expression of pro-angiogenic factors was higher in lichen planus samples compared with inflamed controls. A higher level of CD34 was observed in the deeper parts of the connective tissue of Oral lichen planus (OLP) (P = .04), whereas VEGF and VEGFR2 expressions were higher all through the tissues (respectively, P < .02 and P < .01). The expression of the anti-angiogenic VASH1 was higher in inflamed tissue compared with lichen planus in all sites evaluated (P < .01). CONCLUSIONS: The findings indicate that angiogenic factors are differentially expressed in oral lichen planus compared with inflamed controls, with increased expression of pro-angiogenic factors and decreased anti-angiogenic expression.

Second opinion oral pathology referrals in New Zealand.

Referral for a second opinion is an important aspect of pathology practice, which reduces the rate of diagnostic error and ensures consistency with diagnoses. The Oral Pathology Centre (OPC) is the only specialist oral diagnostic centre in New Zealand. OPC provides diagnostic services to dentists and dental specialists throughout New Zealand and acts as a referral centre for second opinions for oral pathology specimens that have been sent to anatomical pathologists. The aim of this study was to review second opinion referral cases sent to the OPC over a 15-year period and to assess the levels of concordance between the original and final diagnoses. The findings indicated that the majority of referred cases were odontogenic lesions, followed by connective tissue, epithelial and salivary lesions. The most prevalent diagnoses were ameloblastoma and keratocystic odontogenic tumour, followed by oral squamous cell carcinoma. Discordant diagnoses were recorded in 24% of cases. Diagnostic discrepancies were higher in odontogenic and salivary gland lesions, resulting in the change of diagnoses. Second opinion of oral pathology cases should be encouraged in view of the relative rarity of these lesions in general pathology laboratories and the rates of diagnostic discrepancy, particularly for odontogenic and salivary gland lesions.

Forkhead box-P3+ regulatory T cells and toll-like receptor 2 co-expression in oral squamous cell carcinoma.

BACKGROUND: The function of forkhead box-P3 (FoxP3) regulatory T cells (Treg) and toll-like receptor (TLR)2 protein in the oral cancer microenvironment is not fully understood, but evidence from other malignancies suggests it is likely they are involved with tumour development and progression. The aim of this study was to investigate the distribution of FoxP3+cells, TLR2+ cells and double-labelled FoxP3+TLR2+ immune cells in oral squamous cell carcinoma (OSCC), using immunohistochemistry (IHC) and immunofluorescence (IF). METHODS: 25 archival cases of OSCC were immunostained with anti-FoxP3 and anti-TLR2 antibodies. Inflamed hyperplastic oral mucosal tissues were used as controls. The proportion of single-labelled, double-labelled and negative cells was determined. RESULTS: A higher frequency of double-labelled FoxP3+TLR2+ Tregs was observed within the immune cells of OSCC compared to inflamed controls using IHC (p<0.05). Cell-to-cell contact between single-stained TLR2+ cells and FoxP3+ cells was noted. Double IF studies validated demonstration of co-expression of FoxP3+/TLR2+ immune cells in OSCC. CONCLUSION: The presence of FoxP3+TLR2+ cells within the OSCC microenvironment may represent a dendritic cell-dependent pathway capable of inhibiting Treg suppressive activity, potentially enhancing the anti-tumour response. Modulation of TLR2-Treg interactions should be further explored to determine if they have a role in the therapeutic management of OSCC.

Accuracy of single and parallax film and digital periapical radiographs in diagnosing apical periodontitis - a cadaver study.

AIM: To compare the accuracy of film and digital periapical radiography (PR) in detecting apical periodontitis (AP) using histopathological findings as a reference standard. METHODOLOGY: Jaw sections containing 67 teeth (86 roots) were collected from nine fresh, unclaimed bodies that were due for cremation. Imaging was carried out to detect AP lesions using film and digital PR with a centred view (FP and DP groups); film and digital PR combining central with 10˚ mesially and distally angled (parallax) views (FPS and DPS groups). All specimens underwent histopathological examination to confirm the diagnosis of AP. Sensitivity, specificity and predictive values of PR were analysed using rater mean (n = 5). Receiver operating characteristics (ROC) analysis was carried out. RESULTS: Sensitivity was 0.16, 0.37, 0.27 and 0.38 for FP, FPS, DP and DPS, respectively. Both FP and FPS had specificity and positive predictive values of 1.0, whilst DP and DPS had specificity and positive predictive values of 0.99. Negative predictive value was 0.36, 0.43, 0.39 and 0.44 for FP, FPS, DP and DPS, respectively. Area under the curve (AUC) for the various imaging methods was 0.562 (FP), 0.629 (DP), 0.685 (FPS), 0.6880 (DPS). CONCLUSIONS: The diagnostic accuracy of single digital periapical radiography was significantly better than single film periapical radiography. The inclusion of two additional horizontal (parallax) angulated periapical radiograph images (mesial and distal horizontal angulations) significantly improved detection of apical periodontitis.

Implementation of a 'care bundle' improves the management of patients admitted to hospital with decompensated cirrhosis.

BACKGROUND: Since 1970, there has been a 400% increase in liver-related deaths due to the increasing prevalence of chronic liver disease in the United Kingdom (UK). The 2013 UK National Confidential Enquiry into Patient Outcome and Death report found that only 47% of patients who died from alcohol-related liver disease received 'good care' during their hospital stay. AIM: To develop a 'care bundle' for patients with decompensated cirrhosis, aiming to ensure that evidence-based treatments are delivered within the first 24 h of hospital admission. METHODS: This work gives practical advice about how to implement the bundle and examines its effects on patient care at three National Health Service Hospital Trusts in the UK by collecting data on patient care before and after introduction of the bundle. RESULTS: Data were collected on 228 patients across three centres (59% male, median age 53 years). Alcohol-related liver disease was the aetiology of chronic liver disease in 85% of patients. The overall mortality rate during hospital admission was 15%. The audits demonstrated improvements in patient care for patients with a completed care bundle who were significantly more likely to have a diagnostic ascitic performed within the first 24 h (P = 0.020), have an accurate alcohol history documented (P < 0.0001) and be given antibiotics as prophylaxis against infection following a variceal haemorrhage (P = 0.0096). In Newcastle, the bundle completion rate increased from 25% to 90% during the review periods. CONCLUSIONS: The introduction of a care bundle was associated with increased rates of diagnostic paracentesis and antibiotic prophylaxis with variceal haemorrhage in patients with decompensated cirrhosis.

Liver Transplantation for Budd-Chiari Syndrome With Large Solitary Focal Nodular Hyperplasia of the Liver in a Patient With Essential Thrombocythemia: Case Report. [Corrected].

Budd-Chiari syndrome is a rare condition caused by interrupted hepatic venous outflow in the hepatic veins, inferior vena cava, or right atrium. Reports from the literature have delineated on focal nodular hyperplasia (FNH)-like lesions in association with Budd-Chiari Syndrome. To our knowledge, there are no reports about true FNH lesions in patients with Budd-Chiari Syndrome. Focal nodular hyperplasia develops in disorders with aberrant circulation and vasculature. We report a case of Budd-Chiari syndrome in association with large solitary FNH in a 22-year-old man who was referred to our institution with sudden intermittent right upper quadrant abdominal pain, vomiting, diarrhea with pale stool, decreased appetite, dark urine, and abdominal distention for 15 days. Laboratory investigations revealed anemia, thrombocytosis, and abnormal liver function tests and coagulation profile. Imaging revealed hepatic vein thrombosis, confirming Budd-Chiari syndrome, and a 6.2 × 6.1 × 6.8 cm lesion in segment 8 of the liver. Primary cause of Budd-Chiari syndrome was essential thrombocythemia according to bone marrow biopsy and molecular testing results. The patient was treated medically and underwent transjugular intrahepatic portosystemic shunt insertion. The lesion in segment 8 continued to enlarge. Cadaveric liver transplantation was carried out. On gross and histologic examination of the explanted liver, the lesion was found to be a true FNH.

Hepatitis E virus in patients with decompensated chronic liver disease: a prospective UK/French study.

BACKGROUND: In developed countries, hepatitis E is a porcine zoonosis caused by hepatitis E virus (HEV) genotype 3. In developing countries, hepatitis E is mainly caused by genotype 1, and causes increased mortality in patients with pre-existing chronic liver disease (CLD). AIM: To determine the role of HEV in patients with decompensated CLD. METHODS: Prospective HEV testing of 343 patients with decompensated CLD at three UK centres and Toulouse France, with follow-up for 6 months or death. IgG seroprevalence was compared with 911 controls. RESULTS: 11/343 patients (3.2%) had acute hepatitis E infection, and three died. There were no differences in mortality (27% vs. 26%, OR 1.1, 95% CI 0.28-4.1), age (P = 0.9), bilirubin (P = 0.5), alanine aminotransferase (P = 0.06) albumin (P = 0.5) or international normalised ratio (P = 0.6) in patients with and without hepatitis E infection. Five cases were polymerase chain reaction (PCR) positive (genotype 3). Hepatitis E was more common in Toulouse (7.9%) compared to the UK cohort (1.2%, P = 0.003). HEV IgG seroprevalence was higher in Toulouse (OR 17, 95% CI 9.2-30) and Truro (OR 2.5, 95% CI 1.4-4.6) than in Glasgow, but lower in cases, compared to controls (OR 0.59, 95% CI 0.41-0.86). CONCLUSIONS: Hepatitis E occurs in a minority of patients with decompensated chronic liver disease. The mortality is no different to the mortality in patients without hepatitis E infection. The diagnosis can only be established by a combination of serology and PCR, the yield and utility of which vary by geographical location.

Extra-hepatic manifestations of autochthonous hepatitis E infection.

BACKGROUND: Autochthonous (locally acquired) hepatitis E is increasingly recognised in developed countries, and is thought to be a porcine zoonosis. A range of extra-hepatic manifestations of hepatitis E infection have been described, but have never been systematically studied. AIM: To report the extra-hepatic manifestations of hepatitis E virus. METHODS: Retrospective review of data of 106 cases of autochthonous hepatitis E (acute n = 105, chronic n = 1). RESULTS: Eight (7.5%) cases presented with neurological syndromes, which included brachial neuritis, Guillain-Barré syndrome, peripheral neuropathy, neuromyopathy and vestibular neuritis. Patients with neurological syndromes were younger (median age 40 years, range 34-92 years, P = 0.048) and had a more modest transaminitis (median ALT 471 IU/L, P = 0.015) compared to cases without neurological symptoms [median age 64 years (range 18-88 years), median ALT 1135 IU/L]. One patient presented with a cardiac arrhythmia,twelve patients (11.3%) presented with thrombocytopenia, fourteen (13.2%) with lymphocytosis and eight (7.5%) with a lymphopenia, none of which had any clinical consequence. Serum electrophoresis was performed in 65 patients at presentation, of whom 17 (26%) had a monoclonal gammopathy of uncertain significance. Two cases developed haematological malignancies, acute myeloid leukaemia and duodenal plasmacytoma, 18 and 36 months after presenting with acute hepatitis E infection. CONCLUSIONS: A range of extra-hepatic manifestations can occur with hepatitis E. Neurological and haematological features of hepatitis E infection are relatively frequent in this UK cohort, and result in significant morbidity which warrants further study.

Forkhead box P3-positive regulatory T-cells and interleukin 17-positive T-helper 17 cells in chronic inflammatory periodontal disease.

BACKGROUND AND OBJECTIVE: The role of two recently identified and closely related T-helper cell subsets - regulatory T-cells [Tregs; forkhead box P3-positive (FOXP3(+) )] and Th17 cells [interleukin-17-positive (IL-17(+) )] - in periodontal disease is yet to be determined. Tregs are essential in maintaining peripheral tolerance and regulating the immune response. Th17 cells play a critical role in several autoimmune diseases, inflammation and host defence. The aim of this study was to determine the presence of FOXP3(+) Tregs and IL-17(+) cells, and their possible spatial interaction, in diseased periodontal tissues. MATERIAL AND METHODS: Twenty-nine archival tissues with nonspecific gingival inflammation were grouped based on the intensity (minimally or intensely inflamed) and nature (T-cell predominant or B- and plasma-cell predominant) of the inflammatory infiltrate. Using double-labelling immunohistochemistry, the concomitant presence of FOXP3(+) and IL-17(+) cells was determined and their spatial relationship was established. In addition, the proportions of FOXP3(+) and IL-17(+) cells were compared between the groups. RESULTS: Of the 29 gingival specimens investigated, 17 were intensely inflamed (≥ 1000 inflammatory cells per 0.12 mm(2) ) and 12 were minimally inflamed (≤ 600 cells per 0.12 mm(2) ). Based on the percentage of CD19(+) B-cells and plasma cells collectively and CD3(+) T-cells, gingival tissues were also grouped into B- and plasma-cell-predominant gingival tissues (n = 21; 50.7% total B- and plasma cells vs. 19.1% T cells; p < 0.001) and T-cell-predominant gingival tissues (n = 8; 61.0% T-cells vs. 15.2% B- and plasma cells; p = 0.007). More FOXP3(+) cells than IL-17(+) cells were observed in all archival gingival tissues examined. A trend towards an increased number of FOXP3(+) cells was observed for intensely inflamed gingival tissues (6.7%) and for B- and plasma-cell-predominant tissues (6.4%) compared with minimally inflamed gingival tissues (4.6%) and T-cell-predominant gingival tissues (4.5%). However, no statistically significant difference in the mean percentage of FOXP3(+) cells between the groups was observed. Interestingly, FOXP3(+) cells were significantly correlated with the B- and plasma-cell/T-cell ratio in B- and plasma-cell-predominant tissues (r = 0.713, p < 0.001). Overall, there were very few IL-17(+) cells (< 1%). All IL-17(+) cells identified in this study had an ovoid/plasmacytoid morphology and were larger in size compared with adjacent inflammatory cells. IL-17(+) and FOXP3(+) cells were not adjacent to each other in any of the areas examined, suggesting that FOXP3(+) Tregs do not directly interact with IL-17(+) cells in diseased gingival tissues. IL-17(+) /FOXP3(+) cells were not detected in the tissues examined. CONCLUSION: These results show that FOXP3(+) cells are more prominent than IL-17(+) cells in periodontal disease processes, which may suggest a predominant role for FOXP3(+) cells in periodontal disease. Further studies are required to characterize these cells more precisely and to understand, in more detail, their roles in the pathophysiology of periodontal disease.

GIST in Saudi Arabia: multicentric histopathological genetic study of 75 surgically excised cases.

The availability of CD117 (Ckit) immunohistochemical testing in most hospital laboratories has facilitated the diagnosis of GIST in cKit positive cases. The aim of this study was to describe the histopathological variations of GIST in Saudi Arabia. The study involved analysis of paraffin blocks of 75 surgically excised GIST and GIST-like stromal tumors obtained from four major referral hospitals in Saudi Arabia (Riyadh Military Hospital, King Abdulaziz Medical City, King Faisal Specialist Hospital & Research Center and Aramco's hospital) between 1998 and 2009. Patient sex and age were noted in addition to the following tumor variables: size, site, histological grade and type, immunohistochemical profile and genetic analysis of the cKit mutation. The stomach was the commonest site for tumors and spindle cell type was the most frequently seen variant. Further sub classification of the histopathological type was made in order to recognize the morphological pattern of the tumor. The most common tumor grades seen were of low-risk and high-risk groups. There was one case of familial GISTparaganglioma syndrome and the youngest subject was an 8-year-old girl with high-risk spindle cell gastric GIST. Genetic study in 34 cases revealed exon 11 mutations in all of the cKit genes.

Silver solder "tattoo," a novel form of oral pigmentation identified with the use of field emission scanning electron microscopy and electron dispersive spectrography.

OBJECTIVE: The aim of this study was to investigate the use of field emission scanning electron microscopy and electron dispersive spectrography (SEM-EDS) to identify silver solder "tattoo." STUDY DESIGN: SEM-EDS was used to analyze material present in the connective tissue of a patient who presented with bilateral pigmentation of the mandibular lingual gingiva adjacent to the first molars. No dental restorations were present. RESULTS: SEM-EDS analysis identified silver, with no evidence of tin, copper, or mercury. The patient was wearing an orthodontic appliance where brackets had been soldered to the archwire with silver solder. It is hypothesed that the solder underwent electrolytic corrosion with subsequent regrouping of silver ions in the submucosa leading to blue-gray discoloration. CONCLUSION: Spectrography proved to be a powerful diagnostic tool in identifying the metal within the oral mucosa. Attention is drawn to this newly described lesion, which should be included as a differential diagnosis for pigmented oral mucosal lesions.

Clinical features, treatment, and outcome in 102 adult and pediatric patients with localized high-grade synovial sarcoma.

Background. There remains controversy on the routine use of chemotherapy in localized SS. Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed. Results. Median age for AP and PP was 37.6 (range 15-76) and 14 (range 0.4-18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to neoadjuvant chemotherapy, with response rate of 10% and 40%, respectively. 5-year EFS and OS was 69.3 ± 4.8% and 80.3 ± 4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with chemotherapy, compared to 17/46 (37%) In those without. Conclusions. Patients with localized SS have a good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve survival In localized SS remains elusive.

Toll-like receptor 2 is present in the microenvironment of oral squamous cell carcinoma.

BACKGROUND: The aim of this study was to investigate the expression of toll-like receptor 2 (TLR2) on cells associated with oral squamous cell carcinoma, epithelial dysplasia and irritative hyperplasia, using immunohistochemistry. RESULTS: More immune cells expressed TLR2 in carcinoma and dysplasia than in hyperplasia (P<0.001). No hyperplastic samples showed positive TLR2 staining on keratinocytes, whereas keratinocytes in 64% of cases of carcinoma and 74% of cases of dysplasia were TLR2 positive. CONCLUSION: Positive TLR2 expression in the microenvironment suggests activation of immune surveillance against the altered epithelium, whereas TLR2 expression by malignant keratinocytes may be indicative of resistance to apoptosis as a pro-survival mechanism.

Transcriptional profiling of oral squamous cell carcinoma using formalin-fixed paraffin-embedded samples.

Despite the advances in cancer treatment, the 5-year survival rate for oral cancer has not changed significantly for the past 40 years and still remains among the worst of all anatomic sites. Gene expression microarrays have been used successfully in the identification of genetic alterations in cancer development, however, these have hitherto been limited by the need for specimens with good quality intact RNA. Here, we demonstrated the use of formalin-fixed paraffin-embedded tissues in microarray experiments to identify genes differentially expressed between cancerous and normal oral tissues. Forty-three tissue samples were macrodissected and gene expression analyses were conducted using the Illumina DASL assay. We report RNA yield of 2.4 and 0.8 microg/mm(3) from tumour and normal tissues, respectively and this correlated directly with the tissue volume used for RNA extraction. Using unsupervised hierarchical clustering, distinct gene expression profiles for tumour and normal samples could be generated, and differentially expressed genes could be identified. The majority of these genes were involved in regulation of apoptosis and cell cycle, metastasis and cell adhesion including BCL2A1, BIRC5, MMP1, MMP9 and ITGB4. Representative genes were further validated in independent samples suggesting that these genes may be directly associated with oral cancer development. The ability to conduct microarrays on formalin-fixed paraffin-embedded specimens represents a significant advancement that could open up avenues for finding genes that could be used as prognostication and predictive tools for cancer.

Cytological clues in the distinction between phyllodes tumor and fibroadenoma.

BACKGROUND: Fine-needle aspiration (FNA) sensitivity in discriminating between phyllodes tumor and its benign mimicker fibroadenoma (FA) remains low. Because a preoperative categorization of phyllodes tumor is crucial for their appropriate management, the authors undertook this study in an effort to improve the outcome of FNA by identifying reliable distinguishing features. METHODS: FNA smears from 15 and 12 histologically proven cases of phyllodes tumor and FA, respectively, were reviewed. The stromal and epithelial components were qualitatively and quantitatively analyzed. A group of cytological features that may distinguish between phyllodes tumor and FA were identified. Their value and reproducibility in categorizing phyllodes tumor cases were tested. RESULTS: Three major cytological features were exclusively seen in all of, or the vast majority of, the phyllodes tumor cases; fibromyxoid stromal fragments with spindle nuclei (90%), fibroblastic pavements (93%), and appreciable number of spindles cells of fibroblastic nature among dispersed cell population (100%). The identification of these features improved the pick-up rate of phyllodes tumor from 40% to 100% and had substantial (kappa = 0.56-0.73) interobserver and almost perfect (kappa = 0.83) intraobserver reproducibility. There was no significant difference in the epithelial component characteristics between phyllodes tumor and FA. The frequency and degree of atypia in the dispersed cell population correlated well to the histological grade of phyllodes tumor. CONCLUSIONS: FNA has proven to be a reliable test in differentiating between phyllodes tumor and FA with high sensitivity and good reproducibility. The importance of training and continuing education is emphasized.

The histology of acute autochthonous hepatitis E virus infection.

AIM: To document the histological appearances of liver biopsies in autochthonous hepatitis E virus (HEV) infection. METHODS AND RESULTS: Four patients were serologically positive for HEV; three had no traditional risk factors, the fourth had recently returned from China. All four consumed meat products. Liver histology of the three autochthonous (locally acquired) cases showed portal tracts expanded by a severe mixed polymorph and lymphocytic inflammatory infiltrate, with a geographical distribution of polymorphs at the interface and lymphocytes centrally. Moderate to severe interface hepatitis and cholangiolitis were present. There was a striking acinar mixed inflammatory infiltrate made up of polymorphs, lymphocytes and macrophages; frequent apoptotic hepatocytes, focal necrosis, cholestatic rosettes and zone 3 canalicular and cytoplasmic bilirubinostasis were noted. Significant steatosis, megamitochondria and Mallory bodies were not present. There was no evidence of iron, copper or alpha(1)-antitrypsin accumulation. By contrast, the histology of the imported case of HEV infection showed less intense portal and acinar inflammation, no cholangiolitis and no geographical distribution of the portal inflammatory infiltrate. CONCLUSION: The histological appearances of autochthonous HEV infection are sufficiently distinctive to consider the diagnosis in an acute setting and possibly to differentiate it from the endemic form of the disease.

Maxillofacial trauma with emphasis on soft-tissue injuries in Malaysia.

Soft-tissue injuries with or without facial bone involvement are the most common presentation following maxillofacial trauma. The objective of this study was to look at the distribution, pattern and type of soft-tissue injury in relation to aetiology. Records of patients over a period of 5 years (1998-2002), who sustained maxillofacial injuries and were treated at Kajang Hospital, a secondary referral hospital, were reviewed. Out of 313 patients with maxillofacial injuries, 295 patients sustained soft-tissue injuries. Males (79%) between 21 and 30 years old (34%) were the majority of patients. Road-traffic accident was the main cause of soft-tissue injuries (75%) with motorcycle accident being the most frequent (40%). The upper lips (23%) and the lower lips (18%) were the most common extraoral site involved, while the labial mucosa and sulcular areas, both accounting for 21%, were the most common intraoral sites. Stringent road-traffic regulations should be practiced in developing countries, as morbidity arising from road-traffic accidents poses a national economic and social problem.