A novel, somatic, transforming mutation in the extracellular domain of Epidermal Growth Factor Receptor identified in myeloproliferative neoplasm.

We describe a novel ERBB1/EGFR somatic mutation (p. C329R; c.985 T > C) identified in a patient with JAK2V617F Polycythaemia Vera (PV). This substitution affects a conserved cysteine residue in EGFR domain 2 and leads to the formation of a ligand-independent covalent receptor dimer, associated with increased transforming potential. Aberrant signalling from the EGFRC329R receptor is cell type-dependent and in the TF1.8 erythroid cell line expression of this mutant suppresses EPO-induced differentiation. Clonal analysis shows that the dominant JAK2V617F-positive clone in this PV patient harbors EGFRC329R, thus this mutation may contribute to clonal expansion. Somatic mutations affecting other ERBB and related receptor tyrosine kinases are observed in myeloproliferative neoplasms (MPN), and we show elevated EGFR levels in MPN samples, consistent with previous reports. Thus activation of this group of receptors, via multiple mechanisms, may contribute to clonal growth and survival of the JAK2V617F disease clone in MPN.

Clinical, virological and epidemiological characterization of dengue outbreak in Myanmar, 2015.

Hospital-based surveillance was conducted at two widely separated regions in Myanmar during the 2015 dengue epidemic. Acute phase serum samples were collected from 332 clinically diagnosed dengue patients during the peak season of dengue cases. Viremia levels were measured by quantitative real-time PCR and plaque assays using FcγRIIA-expressing and non-FcγRIIA-expressing BHK cells to specifically determine the infectious virus particles. By serology and molecular techniques, 280/332 (84·3%) were confirmed as dengue patients. All four serotypes of dengue virus (DENV) were isolated from among 104 laboratory-confirmed patients including two cases infected with two DENV serotypes. High percentage of primary infection was noted among the severe dengue patients. Patients with primary infection or DENV IgM negative demonstrated significantly higher viral loads but there was no significant difference among the severity groups. Viremia levels among dengue patients were notably high for a long period which was assumed to support the spread of the virus by the mosquito vector during epidemic. Phylogenetic analyses of the envelope gene of the epidemic strains revealed close similarity with the strains previously isolated in Myanmar and neighboring countries. DENV-1 dominated the epidemic in 2015 and the serotype (except DENV-3) and genotype distributions were similar in both study sites.

Assessment of documentation of DSM-IV-TR Criteria A for diagnosis of schizophrenia in psychiatric unit, tertiary hospital, Malaysia.

OBJECTIVE: The purposes of this study were to investigate the documentation of the DSM-IV-TR- Criteria A in diagnoses of schizophrenia and to identify the symptoms associated with over diagnosis of schizophrenia. METHOD: This study involved a retrospective review and analysis of data from case notes. RESULTS: Data of 107 newly diagnosed patients with schizophrenia were keyed in and analyzed using SPSS v 19. The cases were then evaluated for the use of the DSM-IV-TR- Criteria A. Over diagnosis was noted in 37.39% of the patients. Disorganised behaviour (12.5%), affective flattening (12.5%), hallucination (16%) and non-bizarre delusion (18.3%) significantly contributed to the over-diagnosis of schizophrenia. Symptoms such as non-bizarre delusion and hallucination were the most commonly used in over-diagnosing schizophrenia and were statistically significant with p ≤0.05. CONCLUSIONS: There was a significant lack of DSM-IV-TR Criteria A among the data documented to diagnose schizophrenia and non-bizarre delusion and hallucination were the most commonly used in over-diagnosing schizophrenia. This key problem needs to be addressed. The reliability of a diagnosis is indispensable and achievable with the proper clinical application of DSM-IV-TR Criteria A. The DSM-IV-TR Criteria have been perceived to be useful and reliable and is most widely used throughout the world.

Effects of Tamarind (Tamarindus indicus Linn) seed extract on Russell's viper (Daboia russelli siamensis) venom.

Snake bite has been regarded as an important health problem in Myanmar since early 1960's. In the recent years, there has been growing interest in alternative therapies and therapeutic use of natural products, especially those derive from plants. In Myanmar and Indian traditional medicine, various plants have used as a remedy for treating snake bite. The present study was carried out to evaluate the effects of alcohol extract of Tamarind (Tamarindus indica Linn.) seed on some biologic properties of Russell's viper (Daboia russelli siamensis) venom (RVV). The Phospholipase A2 (PLA2) enzyme, coagulase enzyme and caseinolytic enzyme activities of Russell's viper venom (RVV) were reduced when mixed and incubated with the extract. When the RVV and the different amount of extracts were preincubated and injected intramuscularly into mice, all of them survived, but all the mice in the control group died. On the other hand, when RVV were injected first followed by the extract into mice, all of them died. If the extract was injected near the site where Russell's viper venom was injected, all the mice survived for more than 24 hours and the survival time prolonged but they all died within 96 hours. In conclusion, according to the results obtained, the extract neutralizes some biologic properties of the Russell's viper venom and prolonged the survival time if the extract was injected near the site where the Russell's viper venom was injected.

Struma ovarii and the thyroid surgeon.

INTRODUCTION: Struma ovarii is a rare, monodermal, ovarian teratoma. The common presentation is abdominal, with pelvic mass and pain, traditionally managed by gynaecologists. The malignant form is extremely rare and consists of differentiated thyroid cancer. It is rare for struma ovarii to present with features of hyperthyroidism. We present two unusual cases of struma ovarii and discuss the role of the thyroid surgeon in their management. METHODS AND RESULTS: The first case involved a 40-year-old woman with a two-month history of swelling in the lower abdomen. Investigations revealed a mass arising from the left ovary. Surgery revealed a follicular carcinoma arising in a struma ovarii. She underwent a total thyroidectomy prior to radio-iodine therapy. The second case involved a 60-year-old woman who underwent thyroidectomy for thyrotoxicosis. Three months post-operatively, she remained thyrotoxic despite stopping thyroxine. A whole body radio-iodine scan revealed high uptake in the left ovary. Histological analysis of the resected ovary showed benign struma ovarii. CONCLUSION: These two cases highlight the diagnostic and therapeutic role of thyroid surgeons in the management of benign and malignant forms of struma ovarii.

Effects of Tamarind (Tamarindus indicus Linn) seed extract on Russell’s viper (Daboia russelli siamensis) venom

Snake bite has been regarded as an important health problem in Myanmar since early 1960’s. In the recent years, there has been growing interest in alternative therapies and therapeutic use of natural products, especially those derive from plants. In Myanmar and Indian traditional medicine, various plants have used as a remedy for treating snake bite. The present study was carried out to evaluate the effects of alcohol extract of Tamarind (Tamarindus indica Linn.) seed on some biologic properties of Russell’s viper (Daboia russelli siamensis) venom (RVV). The Phospholipase A2 (PLA2) enzyme, coagulase enzyme and caseinolytic enzyme activities of Russell’s viper venom (RVV) were reduced when mixed and incubated with the extract. When the RVV and the different amount of extracts were preincubated and injected intramuscularly into mice, all of them survived, but all the mice in the control group died. On the other hand, when RVV were injected first followed by the extract into mice, all of them died. If the extract was injected near the site where Russell’s viper venom was injected, all the mice survived for more than 24 hours and the survival time prolonged but they all died within 96 hours. In conclusion, according to the results obtained, the extract neutralizes some biologic properties of the Russell’s viper venom and prolonged the survival time if the extract was injected near the site where the Russell’s viper venom was injected.

Do-it-yourself grommets.

In the absence of a healthcare budget enabling the import of ready-made aural grommets, Myanmar ENT surgeons have devised an ingenious 'home-grown' solution. We describe how grommets are made from raw materials bought from the local market.

Thyroidectomy does not cause globus pattern symptoms.

Post-thyroidectomy patients often complain of globus pharyngeus type symptoms. One of the organic pathologies recognized as causing globus pattern symptoms is goitre. We conducted a prospective questionnaire-based study in the thyroid clinic at Hull Royal Infirmary to examine the relationship between goitre, thyroidectomy and globus pattern symptoms by using the Glasgow-Edinburgh Throat Scale. A questionnaire-based study in which 41 consecutive patients due to undergo thyroidectomy prospectively completed the questionnaire pre-operatively and 12 months post-operatively. A subset of 25 randomly selected patients also completed the questionnaire three months post-operatively. Globus symptoms were not worsened by thyroidectomy at three or 12 months. Indeed two of the questioned parameters were significantly improved at three months, and six at one year (p < 0.023). In conclusion, thyroidectomy does not exacerbate globus pharyngeus symptoms. Indeed, in the absence of other clinical causes, when a patient has a World Health Organization (WHO) 2 goitre or greater, thyroidectomy may improve them.

How I do it? Excision of neck lumps under local anaesthesia.

Excisions of neck lesions under local anaesthesia are made technically more difficult by the injection of anaesthetic agent, causing the lesion to become less palpable. Pen marking the lesion can circumvent the problem; however, this marking often disappears after skin preparation. We describe a technique which abolishes this problem.

Effect of a common mutation (D442G) of the cholesteryl ester transfer protein gene on lipids and lipoproteins in children.

Cholesteryl ester transfer protein (CETP) is thought to regulate plasma HDL. Patients with CETP deficiency caused by mutation of the CETP gene [D442G; a missense mutation (Asp442-->Gly)] have been reported to show high plasma HDL levels. However, there are no data available on children with D442G. To determine the effects of plasma CETP and CETP gene mutation (D442G) on lipids and lipoproteins in children, we screened children by PCR and restriction fragment length polymorphism analysis of the CETP gene. Plasma lipids, apolipoproteins, and CETP mass levels were also determined. In the current study, 22 children with D442G were found (21 heterozygotes and a homozygote). A homozygous child showed high plasma HDL level and very low plasma CETP mass. In heterozygous children, plasma concentrations of HDL cholesterol, apo A-I and apo A-II were not increased, whereas plasma CETP mass was significantly decreased. Plasma CETP mass in heterozygous children was correlated with plasma concentrations of total cholesterol, LDL cholesterol, and apo B. Plasma CETP mass in children without D442G was not correlated with the plasma concentration of any lipid or apolipoprotein. All of these data suggest that the D442G mutation, by itself, might not affect HDL metabolism in children. The CETP mass required for efficient HDL-cholesteryl ester clearance in children may be less than that in older subjects.

Induction of acyl-coenzyme A:cholesterol acyltransferase-1 by 1,25-dihydroxyvitamin D(3) or 9-cis-retinoic acid in undifferentiated THP-1 cells.

We have previously shown that acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) protein content increases significantly during the human monocyte-macrophage differentiation process. To gain further insight, we used undifferentiated human monocytic THP-1 cells as a model system with which to examine whether ACAT-1 mRNA and protein content can be increased by treating cells with 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] or with 9-cis-retinoic acid (9-cis-RA), two agents known to upregulate the expression of various genes during the monocyte-macrophage differentiation process. Immunoblot analysis with anti-human ACAT-1 antibodies revealed that ACAT-1 protein was increased by 2.6-fold, using 1,25-(OH)(2)D(3) at a physiological concentration (100 pM). ACAT-1 protein was also increased when using 9-cis-RA, but only at relatively high concentrations (0.1;-1 microM). Northern blot analysis revealed that among the four ACAT-1 mRNA transcripts (2.8, 3.6, 4.2, and 7.0 kb) examined, only the 2.8- and 3.6-kb transcripts were selectively increased. On the basis of enzyme assays in vitro, ACAT activity was increased 3.0-fold by using 100 nM 1,25-(OH)(2)D(3), and 1.8-fold by using 1 microM 9-cis-RA. Together, our results suggest that 1,25-(OH)(3) participates in ACAT-1 gene expression during the monocyte-macrophage differentiation process.

P53 and MDM2 co-expression in tobacco and betel chewing-associated oral squamous cell carcinomas.

Oral cancers of tobacco and betel chewers represents a unique in-vivo model to understand the genotoxic effect of tobacco and betel carcinogens on oncogenes and tumor suppressor genes. Coordinated interactions of p53 and MDM2 play an important role in regulation of critical growth control gene following exposure to DNA damaging agents. The purpose of this study is to determine if the tumor suppressor function of p53 is inactivated by mutation or other alternative mechanisms in carcinogen-induced oral squamous cell carcinoma (SCC), and to investigate the clinicopathological significance of p53 and MDM2 expression. The p53 mutation in oral SCC of tobacco and betel chewers (n=40) was detected by polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP) analysis and immunohistochemistry (IHC) was done to investigate p53 and MDM2 proteins overexpression. The incidence of p53 mutation was relatively low (17.5%), but there was a high prevalence of MDM2 overexpression (72.5%). In the total of 40 cases, IHC phenotype showed p53 positive immunostaining with MDM2 positive immunostaining (p53+/MDM2+) 62.5%, p53 negative immunostaining with MDM2 negative immunostaining (p53-/MDM2-) 15%, p53 positive immunostaining with MDM2 negative immunostaining (p53+/MDM2-) 12.5%, and p53 negative immunostaining with MDM2 positive immunostaining (p53-/MDM2+) 10%. A significant correlation was found between MDM2 and p53 overexpression (p=0.0289). Moreover, p53+/MDM2+ phenotype was significantly associated with poorly differentiated tumors (p= 0.0007). These results conclude that other factors than p53 mutation is likely to be the targets of tobacco/betel carcinogens and MDM2 may play an important role in tobacco/betel chewing-related oral SCCs. Overexpression of MDM2 protein may constitute an alternative mechanism for p53 inactivation.