History, 20th Century ; History, 21st Century ; Humans ; Singapore ; Thoracic Surgery ; history ; Thoracic Surgical Procedures ; history

INTRODUCTIONWe carried out an epidemiological review of cholera in Singapore to determine its trends and the factors contributing to its occurrence.

MATERIALS AND METHODSEpidemiological data of all notified cases of cholera maintained by the Communicable Diseases Division, Ministry of Health, for the period 1992 to 2007 were collated and analysed. Case-control studies were carried out in outbreaks to determine the source of infection and mode of transmission. Linear patterns in age and ethnic distribution of cholera cases were assessed using chi2 test for trend.

RESULTSThere were a total of 210 cholera cases reported between 1992 and 2007. The incidence of cholera declined from 17 cases in 1992 to 7 cases in 2007. About a quarter of the cases were imported from endemic countries in the region. Between 76% and 95% of the reported cases were local residents. Four elderly patients with comorbidities and who sought medical treatment late died, giving a case-fatality rate of 1.9%. Vibrio cholerae 01, biotype El Tor, serotype Ogawa, accounted for 83.8% of the cases. The vehicles of transmission identified in outbreaks included raw fi sh, undercooked seafood and iced drinks cross-contaminated with raw seafood.

CONCLUSIONWith the high standard of environmental hygiene and sanitation, a comprehensive epidemiological surveillance system and licensing and control of food establishments, cholera could not gain a foothold in Singapore despite it being situated in an endemic region. However, health education of the public on the importance of personal and food hygiene is of paramount importance in preventing foodborne outbreaks. Physicians should also maintain a high level of suspicion of cholera in patients presenting with severe gastroenteritis, especially those with a recent travel history to endemic countries.

Adolescent ; Child ; Child, Preschool ; Cholera ; microbiology ; mortality ; Disease Outbreaks ; statistics & numerical data ; Female ; Foodborne Diseases ; epidemiology ; prevention & control ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Population Surveillance ; Singapore ; epidemiology ; Vibrio cholerae O1 ; isolation & purification ; Young Adult

INTRODUCTION: Trauma-induced coagulopathy (TIC) is a form of coagulopathy unique to trauma patients and is associated with increased mortality. The complexity and incomplete understanding of TIC have resulted in controversies regarding optimum management. This review aims to summarise the pathophysiology of TIC and appraise established and emerging advances in the management of TIC. METHODS: This narrative review is based on a literature search (MEDLINE database) completed in October 2020. Search terms used were "trauma induced coagulopathy", "coagulopathy of trauma", "trauma induced coagulopathy pathophysiology", "massive transfusion trauma induced coagulopathy", "viscoelastic assay trauma induced coagulopathy", "goal directed trauma induced coagulopathy and "fibrinogen trauma induced coagulopathy'. RESULTS: TIC is not a uniform phenotype but a spectrum ranging from thrombotic to bleeding phenotypes. Evidence for the management of TIC with tranexamic acid, massive transfusion protocols, viscoelastic haemostatic assays (VHAs), and coagulation factor and fibrinogen concentrates were evaluated. Although most trauma centres utilise fixed-ratio massive transfusion protocols, the "ideal" transfusion ratio of blood to blood products is still debated. While more centres are using VHAs to guide blood product replacement, there is no agreed VHA-based transfusion strategy. The use of VHA to quantify the functional contributions of individual components of coagulation may permit targeted treatment of TIC but remains controversial. CONCLUSION A greater understanding of TIC, advances in point-of-care coagulation testing, and availability of coagulation factors and fibrinogen concentrates allows clinicians to employ a more goal-directed approach. Still, hospitals need to tailor their approaches according to available resources, provide training and establish local guidelines.
Blood Coagulation Disorders/therapy* ; Blood Transfusion ; Hemorrhage ; Hemostasis ; Hemostatics ; Humans

INTRODUCTIONLiver cirrhosis is a common cause of morbidity and mortality and an important burden on the healthcare system. There is limited literature on liver cirrhosis in Singapore. We aimed to describe the epidemiology and clinical characteristics of cirrhotic patients seen in an ambulatory setting in a tertiary referral centre.

MATERIALS AND METHODSThis is a retrospective observational cohort study of cirrhotic patients attending the ambulatory clinic of Singapore's largest tertiary hospital over 5 years. Cirrhosis was diagnosed on characteristic radiological features and/or histology. Aetiology of cirrhosis was determined by history, serology, biochemistry and/or histology. Data on decompensation events and death were retrieved from computerised hospital records.

RESULTSThe study included 564 patients with median follow-up of 85 months. Mean age was 60.9 ± 12.5 years with 63.8% males. Main aetiologies of cirrhosis were chronic hepatitis B (CHB) (63.3%), alcohol (11.2%), cryptogenic (9%) and chronic hepatitis C (CHC) (6.9%). CHB was the predominant aetiology in Chinese and Malays whereas alcohol was the main aetiology in Indians. CHC cirrhosis was more common in Malays than other races. Majority had compensated cirrhosis with 76.8%/18.3%/5%; Child-Pugh A/B/C respectively. Decompensation events occurred in 155 patients (27.5%) and 106 of them (18.8%) died. Diagnosis of cirrhosis via surveillance ultrasound was associated with improved 10-year survival. Age at diagnosis, portal vein thrombosis, Child-Pugh class and decompensation within 1 year of diagnosis were independent predictors of mortality.

CONCLUSIONCHB is the primary cause of liver cirrhosis in Singapore. The major aetiologies of cirrhosis vary amongst the different ethnic groups. Cirrhotics with advanced age, portal vein thrombosis, poorer liver function and early decompensation have a higher mortality risk.

Adult ; Aged ; Ambulatory Care ; Female ; Follow-Up Studies ; Humans ; Liver Cirrhosis ; diagnosis ; epidemiology ; etiology ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Singapore ; epidemiology

Dystrophinopathy is the commonest form of muscular dystrophy and comprises clinically recognized forms, Duchenne dystrophy and Becker dystrophy. Mutations in the dystrophin gene which consist of large gene deletions (65%), duplications (5%) and point mutations (30%) are responsible for reducing the amount of functional dystrophin protein in skeletal muscle fi bres leading to fi bre destruction and disease. The aims of this study are to investigate the detection rate, types and distribution of large gene deletions in Malaysian dystrophinopathy patients using the multiplex polymerase chain reaction (MPCR). MPCR of 18 “hot-spot deletion” regions along the dystrophin gene was performed on DNA from 48 muscle biopsy-confi rmed cases of dystrophinopathy. A positive detection rate of 58% (28/48) was observed, where 84% (16/19) Indian, 35% (6/17) Chinese and 50% (6/12) Malay ethnic groups showed deletions in their dystrophin genes. The Malaysian Indians appear to have a higher prevalence for large gene deletions compared to the Chinese and Malays. Further analyses of 42 confi rmed positive cases (present 28 plus previous 14 cases) by MPCR showed the majority of deletions were in the mid-distal region of the dystrophin gene (81% in exons 45-60). The MPCR is a specifi c and sensitive method for confi rmation of gene deletions responsible for dystrophinopathy.

Purpose: The study aimed to investigate the utility of ultrasonographic (US) findings in predicting the subsequent radiographic parameters of developmental dysplasia of the hips. Methods: In this 12-year retrospective cohort study, all new-born infants with a positive clinical examination or risk factors were included. They were scheduled for hip ultrasonography in the first 3 months, and subsequent radiographs at 1 year of life. The US images were evaluated using the Graf classification, Harcke’s dynamic screening method, and Terjesen’s femoral head coverage method. The radiographic images were evaluated using the acetabular index and femoral head position. The overall US or radiographic findings were considered abnormal if they were classified as abnormal for any of their respective parameters. The overall US and radiographic parameters were correlated. Results: A total of 160 patients were included. The overall US and radiographic parameters showed no statistically significant difference (P=0.050). The sensitivity, specificity, and accuracy of the overall US parameters were 57.1%, 84.9%, and 81.3%, respectively. All three individual US parameters showed no statistically significant differences, with the overall radiographic findings and acetabular index (P>0.05). However, they showed a statistically significant difference, with the position of the femoral head (P<0.001), with the US parameters having an excellent negative predictive value of 100% for identifying an abnormal femoral head position. Conclusion The current study suggests that US findings evaluated in the first 3 months of life showed no statistically significant difference with radiographic findings evaluated at 1 year of life. The US parameters showed an excellent negative predictive value for abnormal femoral head position on radiographs.

E2F-1 and p53 are sequence specific transcription factors that are intimately involved in the regulation of the cell cycle. In addition to their role in cell cycle control, both E2F-1 and p53 have been identified as tumor suppressors and mediators of apoptosis. We have shown previously that adenoviral-mediated E2F-1 overexpression induces efficient apoptosis in colon adenocarcinoma cells. Previous reports have suggested that E2F-1 and p53 cooperate to mediate apoptosis and therefore, in this study, we examined the efficacy of combination gene therapy using adenovirus vectors expressing E2F-1 and p53 in human colon adenocarcinoma cell lines, HT-29 and SW620 (both mutant p53). Cells were treated by mock infection or infection with adenoviral vectors expressing b-galactosidase (LacZ), E2F-1, p53 or a combination of E2F-1 and p53. IC25 concentrations of each virus were estimated and used for each treatment in order to detect any synergistic or cooperative effects on tumor cell death in the combination therapy. By 5 days post infection, E2F-1-overexpressing cells exhibited growth inhibition and approximately 40-50% cell death in both cell lines. Co-expression of p53 with E2F-1 abrogated E2F-1-mediated growth inhibition and cell death. Cell cycle analysis revealed that overexpression of E2F-1 resulted in an accumulation of cells in G2/M phase, while overexpression of p53 resulted in a G1 phase accumulation. However, co-expression of E2F-1 and p53 counteracted each other as fewer cells accumulated in G1 and G2/M when compared to either p53 or E2F-1 alone. Furthermore, co-expression of p53 with E2F-1 resulted in decreased levels of E2F-1 protein expression. Mechanistically, upregulation of the CDK inhibitory protein, p21(WAF1/CIP1), was demonstrated in HT-29 cells following overexpression of either E2F-1, p53 or the combination E2F-1/p53 therapy. However, in SW620 cells, only the cells infected with Ad-p53 alone or in combination resulted in upregulation of p21(WAF1/CIP1). These results suggest that p53 and p21(WAF1/CIP1) may cooperate to inhibit the expression and activity of E2F-1. In conclusion, combination adenoviral vector-mediated E2F-1 and p53 gene transfer was not therapeutically advantageous in this in vitro model of human colon adenocarcinoma.
Adenocarcinoma/*metabolism/pathology ; Adenoviridae/genetics ; Apoptosis/*physiology ; Cell Cycle ; Cell Division ; Colonic Neoplasms/*metabolism/pathology ; Comparative Study ; Cyclins ; Gene Expression ; Gene Therapy ; Gene Transfer Techniques ; *Genes, p53 ; Genetic Vectors ; HT29 Cells ; Human ; Protein p53/genetics/*metabolism ; Recombinant Proteins/metabolism ; Transcription Factors/genetics/metabolism/physiology ; Tumor Cells, Cultured ; Up-Regulation

E2F-1 and p53 are sequence specific transcription factors that are intimately involved in the regulation of the cell cycle. In addition to their role in cell cycle control, both E2F-1 and p53 have been identified as tumor suppressors and mediators of apoptosis. We have shown previously that adenoviral-mediated E2F-1 overexpression induces efficient apoptosis in colon adenocarcinoma cells. Previous reports have suggested that E2F-1 and p53 cooperate to mediate apoptosis and therefore, in this study, we examined the efficacy of combination gene therapy using adenovirus vectors expressing E2F-1 and p53 in human colon adenocarcinoma cell lines, HT-29 and SW620 (both mutant p53). Cells were treated by mock infection or infection with adenoviral vectors expressing b-galactosidase (LacZ), E2F-1, p53 or a combination of E2F-1 and p53. IC25 concentrations of each virus were estimated and used for each treatment in order to detect any synergistic or cooperative effects on tumor cell death in the combination therapy. By 5 days post infection, E2F-1-overexpressing cells exhibited growth inhibition and approximately 40-50% cell death in both cell lines. Co-expression of p53 with E2F-1 abrogated E2F-1-mediated growth inhibition and cell death. Cell cycle analysis revealed that overexpression of E2F-1 resulted in an accumulation of cells in G2/M phase, while overexpression of p53 resulted in a G1 phase accumulation. However, co-expression of E2F-1 and p53 counteracted each other as fewer cells accumulated in G1 and G2/M when compared to either p53 or E2F-1 alone. Furthermore, co-expression of p53 with E2F-1 resulted in decreased levels of E2F-1 protein expression. Mechanistically, upregulation of the CDK inhibitory protein, p21(WAF1/CIP1), was demonstrated in HT-29 cells following overexpression of either E2F-1, p53 or the combination E2F-1/p53 therapy. However, in SW620 cells, only the cells infected with Ad-p53 alone or in combination resulted in upregulation of p21(WAF1/CIP1). These results suggest that p53 and p21(WAF1/CIP1) may cooperate to inhibit the expression and activity of E2F-1. In conclusion, combination adenoviral vector-mediated E2F-1 and p53 gene transfer was not therapeutically advantageous in this in vitro model of human colon adenocarcinoma.
Adenocarcinoma/*metabolism/pathology ; Adenoviridae/genetics ; Apoptosis/*physiology ; Cell Cycle ; Cell Division ; Colonic Neoplasms/*metabolism/pathology ; Comparative Study ; Cyclins ; Gene Expression ; Gene Therapy ; Gene Transfer Techniques ; *Genes, p53 ; Genetic Vectors ; HT29 Cells ; Human ; Protein p53/genetics/*metabolism ; Recombinant Proteins/metabolism ; Transcription Factors/genetics/metabolism/physiology ; Tumor Cells, Cultured ; Up-Regulation