Identification of a novel cyprinid herpesvirus 3 genotype detected in koi from the East Asian and South-East Asian Regions.

Cyprinid herpesvirus 3 (CyHV-3) is a highly contagious virus that causes significant morbidity and mortality in common carp Cyprinus carpio L. and considered to be one of the most important pathogens of koi and common carp worldwide. Cyprinid herpesvirus 3 infected consignments imported from East Asian and South-East Asian regions were identified during quarantine period in Singapore, and virus from a 2005 consignment was successfully isolated in koi fin cells. A combination of sequence analyses and duplex PCR were used to characterize 15 CyHV-3 isolates detected in koi consignments between 2005 and 2011. Sequence analyses of the enlarged 9/5, SphI-5 and TK gene regions identified both the Asian 1 (n = 11) and European 4 (n = 4) genotypes. Duplex PCR analysis of two variable marker regions between ORF29 and ORF30 (marker I) as well as ORF133 and its upstream region (marker II) revealed viruses of genotypes J (I++ II+ ), U/I (I-- II- ), an intermediate genotype (I++ II- ) and a novel genotype, I++ II+Δ , which was identified in viruses from seven different consignments. This novel genotype has a 13-bp deletion in marker II, while maintaining the I++ allele of marker I. The I++ II+Δ genotype may have emerged from East Asian and South-East Asian regions in recent years.

An insight into clinicians' practices in breaking bad news of oral cancer diagnosis.

Communication is an integral component of effective healthcare delivery to patients, and this includes breaking bad news (BBN). However, clinicians in dentistry are rarely exposed to diseases that can negatively and seriously affect an individual's view of their future and pose a mortality risk, except for oral cancer. The aim of this study was to assess clinician practices in BBN of oral cancer diagnosis in Malaysia. An exploratory sequential mixed-methods study design was used. A qualitative study was conducted among 12 clinicians to gather relevant information regarding their practices in BBN of oral cancer diagnosis using a descriptive-interpretive approach. The themes that emerged were preparation for BBN, BBN setting, communication, emotional aspects, and summarizing the session. These themes were used to develop a questionnaire with 34 items. In the quantitative study, this questionnaire was sent to 87 clinicians who had experienced BBN of oral cancer diagnosis in the past 5 years; the response rate was 100%. An arbitrary cut-off score between the third and fourth quartiles was set to distinguish 'good' and 'poor' practice in BBN among the clinicians. The data analysis was performed using IBM SPSS Statistics version 23.0. Overall, at least two-thirds of the clinicians had good practices in BBN of oral cancer diagnosis. The clinicians' designation (oral and maxillofacial surgery consultant/specialist vs dental officer) and BBN experiences were factors associated with their practices in BBN of oral cancer diagnosis.

Headache in hemifacial spasm patients.

OBJECTIVES: To assess prevalence of headaches in patients with hemifacial spasm. To determine whether hemifacial spasm provokes headaches and identifies predictive factors. To evaluate whether botulinum toxin given for hemifacial spasm improves headaches. METHODS: Seventy patients with hemifacial spasm were evaluated for headaches. The relationship of headaches with hemifacial spasm, impact on quality of life (HIT-6), and improvement in headaches from botulinum toxin was recorded. Data on duration, severity, and impact on quality of life (HFS-7) of hemifacial spasm were collected. RESULTS: Hemifacial spasm-related headache was significantly associated with increased hemifacial spasm severity (P < 0.001) and HIT-6 (P = 0.024). Greater hemifacial spasm severity was predictive of hemifacial spasm-related headache (P = 0.006, OR 19.1, 95% CI 2.35-155.64). Botulinum toxin (BTX) for hemifacial spasm improved hemifacial spasm-related headaches (P < 0.001). CONCLUSIONS: Hemifacial spasm can complicate headaches, particularly in patients with greater hemifacial spasm severity. Individually tailored regimens of botulinum toxin may be indicated in these patients.

Complementary therapies in hemifacial spasm and comparison with other movement disorders.

OBJECTIVES: We determined the prevalence, range and factors influencing the use of complementary therapy among hemifacial spasm patients and compared the patterns of use of complementary therapies across different movement disorders in a systematic pooled analysis of published literature. METHODS: A structured questionnaire was administered to 96 hemifacial spasm patients evaluating frequency of complementary therapy use, and factors influencing patients' decision to seek these therapies. We also performed a PubMed search of epidemiology studies on use of complementary therapies in movement disorders. RESULTS: Fifty-one per cent of patients had tried complementary therapies, of which 47% reported some perceived benefit and 4.1% informed their doctor. Acupuncture (71.4%) and facial massage (17.6%) were most commonly used. Complementary therapy use was associated with greater HFS severity. The mean cost of treatment was about $78 per month. We identified eight articles on use of complementary therapies in movement disorders; Parkinson's disease (5), Tourette syndrome (2) and dystonia (1). Twenty-five to 88% of patient had tried complementary therapies, of which 32-70% reported some benefit. Trials of acupuncture (2-63%) and massage (7-38%) were reported across the spectrum of movement disorders studied. Mean cost of complementary therapies varied from 43 to 102 USD per month. CONCLUSION: Complementary therapies are used by over 50% of HFS patients, and the use is correlated with severity of disease. Despite differences in race, culture and population demographics, acupuncture and massage are used by patients across the spectrum of movement disorders.

A comprehensive prognostic analysis of cause-specific mortality in patients with ovarian serous cystadenocarcinoma using a competing-risks model: a case study of the SEER database.

OBJECTIVE: This retrospective study employed a competing-risks analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database to identify precise prognostic factors associated with ovarian serous cystadenocarcinoma (OSCC) in patients. PATIENTS AND METHODS: Patients with OSCC during 2004-2015 were identified in the SEER database, and their clinicopathological, demographic, and survival data were examined. Univariate analysis using Gray's test and the cumulative incidence function was used to evaluate the prognoses of events of interest. The multivariate analysis involved several models, including the Cox proportional hazards, Fine-Gray, and cause-specific (CS) hazard function models, to estimate the hazard functions of competing risks. Hazard ratios were analyzed to identify the reliability of the prognostic factors. RESULTS: Among the 10,400 individuals diagnosed with OSCC, 5,713 died from the illness, and 1,125 died from other causes. The cumulative incidence rate of events of interest was found to be significant for ethnicity, age at diagnosis, histological grade, American Joint Committee on Cancer (AJCC) stage, chemotherapy and surgery status, tumor size, marital status, and local lymph node metastases (p<0.05). The multivariate analysis revealed that ethnicity, histological grade, surgery and chemotherapy status, age at diagnosis, AJCC stage, marital status, and distant metastases were independent prognostic factors in the Cox model (p<0.05). Finally, the Fine-Gray and CS models demonstrated that ethnicity, histological grade, surgery and chemotherapy status, age at diagnosis, AJCC stage, tumor size, marital status, and combination summary stage were all identified as independent prognostic factors (p<0.05). CONCLUSIONS: This study determined the risk factors for OSCC using a competing risk analysis model established by the SEER database. The findings can help clinicians understand OSCC better and provide more accurate medical support to affected patients.

A prospective study to compare the diagnostic performance of breast elastography versus conventional breast ultrasound.

AIM: To compare the diagnostic performance of breast elastography versus conventional ultrasound in the assessment of breast lesions. MATERIALS AND METHODS: The study was approved by the hospital's institutional review board. A prospective study involving 99 consecutive women who gave informed consent were enrolled from September 2007 to March 2008. One hundred and ten breast lesions were evaluated separately by conventional ultrasound, elastography and combined conventional ultrasound with elastography. Ultrasound assessment was based on the BIRADS classification, whereas elastographic assessment was based on strain pattern and the elastographic size ratios. Histological diagnosis was used as the reference standard. The sensitivity, specificity, and accuracy of each technique were compared. RESULTS: The mean age of the patients was 46.7 years. Twenty-six lesions were malignant and 84 were benign. Sensitivity, specificity, and accuracy were 88.5, 42.9 and 53.6%, respectively, for conventional ultrasound, 100, 73.8, and 80%, respectively, for elastography, and 88.5, 78.6, and 80.9%, respectively, for combined imaging. The specificity and accuracy of elastography and combined imaging were significantly better than that of conventional ultrasound (p<0.0001), whereas there was no statistically significant difference in the sensitivity between all three groups. Two-thirds (66.7%) of sonographic false-positive lesions had benign elastogram findings, which might have been spared from biopsy. CONCLUSION: This initial experience with ultrasound breast elastography showed that it was more specific and more accurate than conventional ultrasound. Combining elastography with ultrasound improved specificity and accuracy of ultrasound and can potentially reduce unnecessary breast biopsies.

A 6-year review of surgical morbidity and oncological outcome after high anterior resection for colorectal malignancy with and without splenic flexure mobilization.

OBJECTIVE: High anterior resection (HAR) for colorectal cancer is traditionally performed with routine mobilization of the splenic flexure. This is a retrospective review of mortality and morbidity following HAR in which the splenic flexure has been preserved. METHOD: From a prospective database, all patients who had undergone elective HAR for colorectal cancer between 1999 and 2005 were identified. Morbidity, mortality, pathology and survival data for patients having HAR with and without splenic flexure mobilization were analysed. RESULTS: A total of 707 patients were identified. Five hundred and thirty-one had HAR with preservation of the splenic flexure. In these patients outcome was: anastomotic leak (0.4%), wound infection (3.6%), anastomotic stricture (0.4%) and 30-day mortality (0.9%). No statistical significant difference was found for postoperative morbidity (P = 0.1926), 30-day mortality (P =0.3285), lymph node harvest (P = 0.2127) or survival (P = 0.1457) compared with patients in whom the splenic flexure was mobilized. Longitudinal resection margins were greater following HAR with splenic flexure mobilization (P < 0.0001). CONCLUSION: No morbidity, oncological or survival disadvantage in performing splenic flexure preserving HAR was found.

The teaching of pathology.

A/Professor Chong Siew Meng relates the teaching of Pathology in the Medical School since 1905. The Pathology Department of the College of Medicine is closely associated with the Department of Pathology of the Government Medical Service. Pathologists in the Government Medical Service taught medical students till 1955 when the chair of Pathology was filled by Professor R Kirts. Undergraduates and postgraduate teaching and research in the department are described briefly.

School-administered weekly iron-folate supplements improve hemoglobin and ferritin concentrations in Malaysian adolescent girls.

BACKGROUND: Iron deficiency and its consequent anemia constitute the commonest micronutrient deficiency in the world. OBJECTIVE: We investigated whether long-term, weekly iron-folate supplements administered at school would improve hemoglobin and ferritin concentrations in adolescent girls, including those with mild-to-moderate anemia and hemoglobin concentrations indicating borderline anemia. DESIGN: Subjects were 266 girls with hemoglobin concentrations of 80-119.9 g/L (group A) and 358 girls with hemoglobin concentrations of 120-130 g/L (group B) who were otherwise healthy. Two hundred sixty-six girls in group A and 268 girls in group B were randomly assigned to receive either 60 or 120 mg Fe plus 3.5 mg folic acid weekly for 22 wk. Ninety of the girls in group B were randomly assigned to receive only 5 mg folic acid weekly. Capillary hemoglobin and plasma ferritin were measured at baseline and after 12 and 22 wk of supplementation. RESULTS: By the end of the study, 2% of the girls had dropped out and > 96% had taken > or = 20 of the 22 tablets; side effects were minimal. Mean plasma ferritin increased significantly in all iron-supplemented groups, independently of initial hemoglobin values and iron doses. Ferritin concentrations decreased in the girls supplemented with folic acid only. As expected, hemoglobin responses to iron were higher in group A than in group B and increases were positively correlated with initial plasma ferritin. Hemoglobin failed to respond to folate supplementation if initial plasma ferritin concentrations were low. Mean hemoglobin increased significantly and consistently in relation to the length of treatment. CONCLUSION: Long-term, weekly iron-folate supplementation was found to be a practical, safe, effective, and inexpensive method for improving iron nutrition in adolescent schoolgirls.

Evaluation of somnolence in Parkinson's disease: comparison with age- and sex-matched controls.

The authors found a significantly higher prevalence of daytime somnolence in 201 patients with PD compared with 214 age- and sex-matched healthy control subjects (Epworth Sleepiness Scale score 5.6 vs 4.6). The prevalence of "sleep attacks" (SA) was about seven times higher in patients with PD than in control subjects (13.9% vs 1.9%; p < 0.0005). Multivariate analysis demonstrated that a higher dose of levodopa and longer duration of disease significantly predicted for SA in patients with PD. Epworth Sleepiness Scale scores of > or =10 had 71.4% sensitivity and 88.4% specificity for SA.

Plasma macrophage colony-stimulating factor and P-selectin levels in malaria-associated thrombocytopenia.

Thrombocytopenia is a common finding in malaria. In clinical trials, recombinant macrophage colony-stimulating factor (M-CSF) causes a reversible, dose-dependent thrombocytopenia, and high M-CSF has been reported in autoimmune thrombocytopenias. P-selectin, which is secreted into the plasma following platelet/endothelial activation or damage, is elevated in certain consumptive thrombocytopenic disorders. The relationships between thrombocytopenia, M-CSF and P-selectin were analysed in 63 patients with severe (n = 13) or uncomplicated (n = 26) P. falciparum (PF) or P. vivax (PV) malaria (n = 24). On admission, 69% of PF patients and 75% of PV patients were thrombocytopenic (platelets < 150 x 10(9)/l). M-CSF was elevated in PF (3021 +/- 1844 pg/ml) and PV (2602 +/- 1668 pg/ml) patients, compared to controls (589 +/- 200 pg/ml). The platelet count was inversely correlated with M-CSF in PF (r = -0.681), and in PV malaria (r = -0.548). Elevated P-selectin was found in severe PF malaria, but not in PV malaria. Severe PF malaria was associated with marked thrombocytopenia, very high M-CSF, elevated P-selectin and compelling evidence of disseminated intravascular coagulopathy (DIC). Platelet counts, M-CSF and P-selectin returned to control values in 7-14 days. These data suggest that elevated M-CSF in malaria, by enhancing macrophage activity, may result in increased macrophage-mediated platelet destruction. Further, platelet/endothelial activation or damage, as measured by P-selectin, or DIC could intensify thrombocytopenia in severe PF malaria, but does not appear to contribute to thrombocytopenia in uncomplicated PF or PV malaria.

Increased production of interferon-gamma by tumour infiltrating T lymphocytes in nasopharyngeal carcinoma: indicative of an activated status.

Undifferentiated nasopharyngeal carcinomas (UNPC) are characterised by an association with Epstein-Barr virus and an abundant lymphoid stroma. We studied the functional status of the infiltrating T cells in ten UNPC biopsies using an immunohistochemical approach. Twelve non-NPC biopsies were included as controls. Tumour cells of UNPC were positive for HLA class I (10/10) and II (8/10), LMP1 (3/10), and CD86 (6/10). Tumour infiltrating T cells (TILs) were detected with antibodies directed at CD3, CD4, and CD8, and shown to be comparable to that in the control biopsies. Although expression of CD28 was shown to be decreased in TILs, expression of CD25 and IFN-gamma at a relatively high percentage could be consistently detected in the UNPC biopsies. These data suggest that TILs in UNPC are in an activated status, and this T cell response is possibly directed at the tumour cells.

A distinct expression of CC chemokines by macrophages in nasopharyngeal carcinoma: implication for the intense tumor infiltration by T lymphocytes and macrophages.

Nasopharyngeal carcinoma (NPC) is characterized by harboring Epstein-Barr virus genes in the tumor cells and an intense infiltration of leukocytes in the tumor tissue. These infiltrating cells are mainly composed of T lymphocytes and macrophages. The mechanism of this intense infiltration has long been a puzzle. We attempted to address this issue by studying the expression of CC chemokines, which are responsible for recruiting both T cells and macrophages, by an immunohistochemical approach. In biopsies obtained from nasopharynx of 17 NPC patients that contained tumor cells, expression of macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, macrophage chemoattractant protein-1 (MCP-1), MCP-2, MCP-3, and RANTES was detected in the tumor-infiltrating cells, with MIP-1alpha and MCP-1 found in nearly all biopsies and the others relatively less frequently. Furthermore, expression of interferon-gamma (IFN-gamma) was also observed in tumor-infiltrating cells. In contrast, CC chemokines and IFN-gamma were rarely expressed in the 13 control biopsies that were either normal or with nonspecific inflammation, and in 4 biopsies from untreated NPC patients that contained no tumor cells. Using an immunofluorescent double-staining method, MIP-1alpha and MCP-1 were identified to be associated with macrophages, and IFN-gamma with T cells. Moreover, expression of CCR2 and CCR5, the receptors for these chemokines, was also detected in the tumor-infiltrating cells. These data indicate that the intense tumor infiltration by T cells and macrophages is a result of active recruitment. It seems possible that the intense infiltration of leukocytes in NPC tumor tissue is initiated by the activated tumor-reactive T cells. T cells migrate into the tumor tissue in an antigen-specific mode, and IFN-gamma secreted from these pioneer T cells activates tissue macrophages to express CC chemokines, especially MIP-1alpha and MCP-1, which consequently recruit more T cells and macrophages into the tumor tissue.

Lymphocytic gastritis-like T cell lymphoma: molecular evidence of an unusual recurrence.

This report describes a patient with a gastric biopsy specimen showing histomorphological and immunohistochemical appearances indistinguishable from those usually present in lymphocytic gastritis, a rare condition of unknown aetiology with a distinctive phenotype. The patient had a history of a biopsy confirmed T cell non-Hodgkin lymphoma at two anatomical sites (bladder and stomach), which was subsequently treated. Molecular analysis of the T cell receptor (TCR) gamma chain gene rearrangements showed a distinct monoclonal T cell population in the bladder and gastric biopsies. The same analysis in the lymphocytic gastritis-like biopsy sample showed a monoclonal population with identical base pair size to that identified in the other specimens. This report highlights the importance of TCR gene rearrangement analysis in the diagnosis of unusual gastric inflammation, and the use of capillary electrophoresis based polymerase chain reaction in the follow up of lymphoproliferative disorders.

Dose-dependent protective effect of coffee, tea, and smoking in Parkinson's disease: a study in ethnic Chinese.

INTRODUCTION: Few studies have examined the relationship of coffee and tea in Parkinson's disease (PD). The potential protective effect of coffee intake and risk of PD has not been studied in a Chinese population. There is a high prevalence of caffeine takers among Chinese in our population. OBJECTIVE: We undertook a case control study to examine the relationship between coffee and tea drinking, cigarette smoking, and other enviromental factors and risk of PD among ethnic Chinese in our population. METHODS AND RESULTS: 300 PD and 500 population controls were initially screened. Two hundred case control pairs matched for age, gender, and race were finally included in the analysis. Univariate analysis revealed significant association of PD with coffee drinking (p<0.0005), tea drinking (p=0.019), alcohol drinking (p=0.001), cigarette smoking (p<0.0005), and exposure to heavy metals (p=0.006). Conditional logistic regression analysis demonstrated that amount of coffee drunk (OR 0.787, 95%CI 0.664-0.932, p=0.006), amount of tea drunk (OR 0.724, 95%CI 0.559-0.937, p=0.014), number of cigarettes smoked (OR 0.384, 95%CI 0.204-0.722, p=0.003), history of heavy metal and toxin exposure (OR 11.837, 95%CI 1.075-130.366, p=0.044), and heart disease (OR 5.518, 95%CI 1.377-22.116, p=0.016) to be significant factors associated with PD. One unit of coffee and tea (3 cups/day for 10 years) would lead to a 22% and 28% risk reduction of PD. One unit of cigarette smoke (3 packs/day for 10 years) reduced the risk of PD by 62%. CONCLUSIONS: We demonstrated a dose-dependent protective effect of PD in coffee and tea drinkers and smokers in an ethnic Chinese population. A history of exposure to heavy metals increased the risk of PD, supporting the multifactorial etiologies of the disease.

The natural history of spontaneous osteonecrosis of the medial tibial plateau.

The natural history of spontaneous osteonecrosis of the medial tibial plateau remains controversial and incomplete. We have studied 21 patients (aged between 53 and 77 years) with clinical and scintigraphic features of spontaneous osteonecrosis of the medial tibial plateau who were observed prospectively for at least three years (37 months to 8.5 years). The mean duration of follow-up was 5.6 years. The mean duration of symptoms at presentation was 4.7 weeks (3 days to 12 weeks). Radiographs of the affected knee at the first visit were normal in 15 patients and mildly arthritic in six. The characteristic radiographic lesion of osteonecrosis was noted at presentation in five of the mildly arthritic knees and during the evolution of the disease in eight of the radiographically normal knees. During the follow-up, subchondral sclerosis of the affected medial tibial plateau was noted in 16 knees. There are three distinct patterns of outcome: 1) acute extensive collapse of the medial tibial plateau in two knees within three months of onset; 2) rapid progression to varying degrees of osteoarthritis in 12 knees, in eight within a year, in all within two years and deterioration of the pre-existing osteoarthritis in three; and 3) complete resolution in four knees, two of which were normal at presentation and two mildly osteoarthritic. The two patients with acute extensive collapse and three who had rapid progression to severe osteoarthritis required total knee arthroplasty. We conclude that osteonecrosis of the medial tibial plateau progresses in most cases to significant degenerative disease of the knee.

The 3-week sulphasalazine syndrome strikes again.

A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called "3-week sulphasalazine syndrome", a rare, but often fatal, immunoallergic reaction to sulphasalazine.

Bilateral carcinoid tumor of the breast. Report of a case with diagnosis by fine needle aspiration cytology.

A case of bilateral carcinoid tumors of the breast was studied by cytology, histology, immunohistochemistry and electron microscopy. The preoperative aspiration cytologic findings strongly suggested a carcinoid tumor of the breast. The differential diagnosis with fine needle aspiration cytology of other breast lesions, the bilaterality of the condition and terminology are discussed.

Aspiration cytology of liver abscesses. With an emphasis on diagnostic pitfalls.

Clinical and imaging features of liver abscesses are not specific. Necrotic hepatic neoplasms, primary or secondary, can mimic abscesses, and vice versa. Thirty-eight patients who had cytologic confirmed abscesses were analyzed. There was clinical, radiologic and cytologic concurrence in 27 patients. In six cases the clinically suspicious lesion turned out to be inflammatory. The remaining five were malignant. There were four amebic and three tuberculous cases in this series. Cytologically, pyogenic abscesses contained a heavy, neutrophilic, inflammatory exudate with nuclear debris. By comparison, amebic cases contained more necrotic debris, with degenerating hepatocytes and fewer inflammatory cells. Acid-fast bacilli were identified in two tuberculous abscesses; however, only one contained caseous necrotic material and epithelioid cells. A potential pitfall in the cytologic diagnosis of a case of inflammatory pseudotumor is emphasized. The diagnosis of liver abscess should be established by clinical and imaging findings in conjunction with needle aspiration.