Experience of a screening centre for influenza A/H1N1: the first 50 days.

BACKGROUND: The authors' emergency department (ED) served as Singapore's screening centre for influenza H1N1 cases. The aims of the study were to describe their screening experience and to compare clinical and laboratory features of H1N1 versus seasonal flu cases. METHODOLOGY: The authors conducted a prospective observational study on consecutive patients aged 16 years and above presenting to a busy, urban ED for H1N1 screening over 50 days. Clinical, laboratory, radiological and PCR data were collected from the hospital electronic databases. Primary outcomes were proportions of confirmed H1N1 cases and their distribution of clinical, laboratory and radiological features. Secondary outcomes were comparison of clinical and laboratory features of H1N1 versus seasonal flu cases. Data were analysed using descriptive statistics and univariate analysis was used to compare factors between the two groups. A p value <0.05 was considered statistically significant. RESULTS: 1205 patients were screened. 31 (2.6%) and 133 (11%) of them had H1N1 and seasonal flu infections, respectively. The two groups had similar symptoms. There were six clinical and two laboratory features with statistically significant differences between H1N1 and seasonal flu cases. Clinical factors were travel or contact history, median age, respiratory rate, diastolic blood pressure and length of hospital stay. Laboratory factors were median platelet and lymphocyte counts. CONCLUSIONS: The authors report their experience as the nation's H1N1 screening centre. They identified factors that were different between H1N1 and seasonal flu cases. Future research is needed to elucidate if and how this information can be used as a screening tool for H1N1.

DLEC1 is a functional 3p22.3 tumour suppressor silenced by promoter CpG methylation in colon and gastric cancers.

Promoter CpG methylation of tumour suppressor genes (TSGs) is an epigenetic biomarker for TSG identification and molecular diagnosis. We screened genome wide for novel methylated genes through methylation subtraction of a genetic demethylation model of colon cancer (double knockout of DNMT1 and DNMT3B in HCT116) and identified DLEC1 (Deleted in lung and oesophageal cancer 1), a major 3p22.3 TSG, as one of the methylated targets. We further found that DLEC1 was downregulated or silenced in most colorectal and gastric cell lines due to promoter methylation, whereas broadly expressed in normal tissues including colon and stomach, and unmethylated in expressing cell lines and immortalised normal colon epithelial cells. DLEC1 expression was reactivated through pharmacologic or genetic demethylation, indicating a DNMT1/DNMT3B-mediated methylation silencing. Aberrant methylation was further detected in primary colorectal (10 out of 34, 29%) and gastric tumours (30 out of 89, 34%), but seldom in paired normal colon (0 out of 17) and gastric (1 out of 20, 5%) samples. No correlation between DLEC1 methylation and clinical parameters of gastric cancers was found. Ectopic expression of DLEC1 in silenced HCT116 and MKN45 cells strongly inhibited their clonogenicity. Thus, DLEC1 is a functional tumour suppressor, being frequently silenced by epigenetic mechanism in gastrointestinal tumours.

24-Hour observational ward management of diabetic patients presenting with hypoglycaemia: a prospective observational study.

BACKGROUND: A 24 h observational ward was set up in the study hospital emergency department (ED) in September 2005 to manage a group of patients with specific conditions including hypoglycaemia that require only short focused inpatient care. AIM: To evaluate the efficacy and safety of the management of hypoglycaemia in the observational ward via criteria of successful discharge of patients from the observational ward within 24 h and the recurrence of hypoglycaemia after discharge. METHODS: Hypoglycaemic patients admitted to the observational ward had their treatment and evaluation performed within 24 h. A protocol based on current available literature was formulated. Data were collected prospectively and included patient demographics, the duration and type of diabetes mellitus, current medications and treatment given. Patients were discharged only after a set of strict discharge criteria was fulfilled, and were followed up by telephone interviews at 7 and 28 days after discharge. RESULTS: A total of 203 patients were recruited. Of these, 170 (83.7%) patients were discharged and 33 (16.3%) were transferred to an inpatient team for a longer period of treatment. The median length of stay in the observational ward was 23.0 h. Of the 170 patients discharged, 151 (88.8%) were contacted at 7 and 28 days after discharge. Six patients had symptoms of recurrent hypoglycaemia, two of whom reattended the ED and had to be admitted. The remaining four patients had mild symptoms that were self-managed at home. Two other patients reattended for conditions not related to hypoglycaemia. Nineteen patients could not be contacted, but there was no record of any reattendances at the ED among this group of patients. CONCLUSION: There are currently no recommendations regarding the length of stay in hospital for patients with severe hypoglycaemia. This study shows that selected patients can be treated effectively and safely in a 24 hour observational ward.

The major 8p22 tumor suppressor DLC1 is frequently silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal, and cervical carcinomas, and inhibits tumor cell colony formation.

Identification of tumor suppressor genes (TSG) silenced by methylation uncovers mechanisms of tumorigenesis and identifies new epigenetic tumor markers for early cancer detection. Both nasopharyngeal carcinoma (NPC) and esophageal carcinoma are major tumors in Southern China and Southeast Asia. Through expression subtraction of NPC, we identified Deleted in Liver Cancer 1 (DLC1)/ARHGAP7 (NM_006094)--an 8p22 TSG as a major downregulated gene. Although expressed in all normal tissues, DLC1 was silenced or downregulated in 11/12 (91%) NPC, 6/15 (40%) esophageal, 5/8 (63%) cervical and 3/9 (33%) breast carcinoma cell lines. No genetic deletion of DLC1 was detected in NPC although a hemizygous deletion at 8p22-11 was found by 1-Mb array-CGH in some cell lines. We then located the functional DLC1 promoter by 5'-RACE and promoter activity assays. This promoter was frequently methylated in all downregulated cell lines and in a large collection of primary tumors including 89% (64/72) NPC (endemic and sporadic types), 51% (48/94) esophageal, 87% (7/8) cervical and 36% (5/14) breast carcinomas, but seldom in paired surgical marginal tissues and not in any normal epithelial tissue. The transcriptional silencing of DLC1 could be reversed by 5-aza-2'-deoxycytidine or genetic double knock-out of DNMT1 and DNMT3B. Furthermore, ectopic expression of DLC1 in NPC and esophageal carcinoma cells strongly inhibited their colony formation. We thus found frequent epigenetic silencing of DLC1 in NPC, esophageal and cervical carcinomas, and a high correlation of methylation with its downregulation, suggesting a predominant role of epigenetic inactivation. DLC1 appears to be a major TSG implicated in the pathogenesis of these tumors, and should be further tested as a molecular biomarker in patients with these cancers.

Rhabdomyolysis following dengue virus infection.

We describe a 27-year-old man who developed prolonged myalgia and dark red-coloured urine following dengue virus infection. The patient was found to have raised serum creatine kinase levels, consistent with rhabdomyolysis. He was treated with intravenous hydration and recovered uneventfully. Despite dengue fever being endemic in Singapore and South-east Asia, this is the first case report of such complication in this region.

Are the World Health Organisation case definitions for severe acute respiratory distress syndrome sufficient at initial assessment?

INTRODUCTION: On March 13, 2003, Singapore doctors were alerted about an outbreak of atypical pneumonia that became known as severe acute respiratory syndrome (SARS). We now describe a series of patients that did not fit World Health Organisation (WHO) case definitions for SARS at initial assessment. METHODS: The Ministry of Health, Singapore centralised SARS cases in the study hospital and its emergency department (ED) became the national screening centre. A screening questionnaire and a set of admission criteria based on WHO case definitions were applied. Patients discharged from ED were tracked via telephone surveillance and recalled if necessary. A retrospective review was done of patients who did not fit WHO definitions initially, were discharged and had re-attended. RESULTS: During the outbreak, 11,461 people were screened for SARS. Among 10,075 (87.9 percent) discharged from the ED, there were 28 re-attendees diagnosed to have SARS later, giving an undertriage rate of 0.3 percent. Among the 28, six (21.4 percent) did not complain of fever and 22 (78.6 percent) had temperatures less than 38.0 degrees Celsius during their first ED visit. One patient was screened to have all three criteria but during consultation, the contact history was found to be unrelated to the known "hot spots". The initial mean temperature was 37.6 degrees Celsius (standard deviation [SD] 0.8), which increased significantly (p-value equals 0.04) to 38.0 degrees Celsius (SD 0.8) during their subsequent visit. Chest radiographs with infective changes increased significantly (p-value equals 0.009) from 16 percent to 52.4 percent over the two ED visits. CONCLUSION: The WHO case definitions were helpful in evaluating majority of SARS patients initially. However under-triage at ED is inevitable, with a 0.3 percent under-triage in our study population. In this group and asymptomatic individuals who came for screening, a tracking and recall system helped to ensure their timely return to the ED.

Presentation of severe acute respiratory syndrome (SARS) patients in a screening centre.

INTRODUCTION: On 22 March 2003, the Ministry of Health, Singapore, designated Tan Tock Seng Hospital as the nationwide severe acute respiratory syndrome (SARS) hospital and its Emergency Department (ED) took over the role as the screening center for SARS on 26 March 2003. We describe the initial clinical characteristics of probable or suspect SARS patients that presented to the ED. METHODS: A retrospective study of patients who were admitted through the ED and subsequently diagnosed to have probable SARS and suspect SARS was done. The data of these patients from the ED log were reviewed and analysed. RESULTS: From 13 March 2003 to 31 May 2003, 11,461 patients were screened for SARS and 1,386 patients were admitted. Of these, 117 patients were diagnosed to have probable SARS and 146 suspect SARS. Their mean age was 36.7 years (range 1-80). Among these patients, there were 122 men (46.4 percent), and 205 were Singaporeans (77.9 percent). 13 patients had no initial contact history upon presentation to the ED. The mean duration between onset of symptom to presentation to the ED was 3.1 days. Travel history was less common in probable SARS cases than in suspect SARS cases as the epidemic was due mainly to local transmission. Fever was the most common presenting symptom (91.6 percent), and gastrointestinal symptoms were the least (6.9 percent). In the ED, 249 (94.7 percent) patients had chest radiographs and 86 (32.7 percent) had full blood count done. 22.2 percent of probable SARS patients had normal chest radiographs when they first presented to the ED. CONCLUSION: The World Health Organisation criteria were important screening tools and admission guides, but should not be strictly followed. It was difficult to differentiate between probable and suspect SARS patients in the ED.

Castleman's disease of the neck: a description of four cases on contrast-enhanced CT.

Castleman's disease of the neck is an uncommon benign lymphoproliferative disease that usually presents as homogeneously enhancing enlarged lymph nodes on contrast-enhanced CT scan. We described the appearance of four confirmed cases of Castleman's disease of the neck on contrast-enhanced CT scan. Three of these presented as a solitary enhancing lymph node and the fourth case presented with multiple bilateral enhancing lymph nodes. A central non-enhancing area was present in two of the three cases that presented as a solitary node. Pathological correlation of one of these cases showed that this was due to a central fibrotic scar. One of the enhancing nodes in the fourth case with multiple and bilateral lymphadenopathy also contained a central non-enhancing area. We would like to propose that if a central non-enhancing scar is observed in an enhancing lymph node in the neck on CT scan, Castleman's disease should be considered as a possible diagnosis.

Non-traumatic acute paraplegia caused by cervical disc herniation in a patient with sleep apnoea.

A 57-year-old man with obstructive sleep apnoea presented with acute progression of myelopathy into paraplegia resulting from cervical disc herniation at C4-C5 and C5-C6 levels. There was no associated history of trauma. Rapid progress to paraplegia from non-traumatic cervical disc herniation rarely occurs. Diagnostic and treatment modalities are discussed. The possible relationship between cervical myelopathy and sleep apnoea is also discussed.

Profile of admissions to an acute dialysis care unit.

The profile of admissions to an acute dialysis care facility of the National University Hospital Renal Centre, Singapore was studied in an attempt to identify the needs of these patients so that admissions may be possibly reduced. All patients above the age of 18 years who were admitted to the dialysis centre in the National University Hospital for dialysis between 1 Jan 2000 and 31 Mar 2000 inclusive were studied. A total of 124 patients were studied. Almost all the patients had end stage renal failure. The commonest cause of end stage renal failure was diabetic nephropathy (58.8%). There were a total of 157 admissions. Most of the admissions were associated with end stage renal failure (96%). Vascular access problems caused 40% of all admissions and 68% of all multiple admissions. The data suggest that a dialysis facility in a multidisciplinary acute hospital needs to meet the requirements of mainly patients who are already in end stage renal failure, those who have vascular access problems and those who have diabetes.

Residual cervical lymphadenopathy after definitive treatment of nasopharyngeal carcinoma: fine needle aspiration cytology, computed tomography and histopathological findings.

BACKGROUND: Patients with nasopharyngeal carcinoma may have residual cervical lymphadenopathy after definitive treatment of the primary tumour and regional cervical nodal disease. Whether such lymphadenopathy truly represents persistent disease is unclear. There are few published studies addressing this clinical problem. METHODS: We retrospectively and systematically reviewed the clinical records of 12 patients with nasopharyngeal carcinoma who had presented to a tertiary academic hospital, over an 11-year period, with suspected persistent cervical nodal disease after definitive radiotherapy or concurrent chemoradiotherapy. Findings on fine needle aspiration cytology and computed tomography scanning were correlated with final histopathological results. RESULTS: The incidence of negative neck dissection was 41.7 per cent. The positive and negative predictive values of fine needle aspiration cytology in identifying disease were 100 and 42.9 per cent, respectively. Computed tomography scanning had a positive predictive value of 58.3 per cent in identifying disease. CONCLUSION: In patients treated definitively for nasopharyngeal carcinoma, residual cervical lymphadenopathy may not represent persistent disease. Head and neck surgeons involved in the management of these patients should bear in mind the current limitations of fine needle aspiration cytology and computed tomography in confirming the diagnosis pre-operatively. Salvage neck dissection may over-treat some of these patients.

A novel isoform of the 8p22 tumor suppressor gene DLC1 suppresses tumor growth and is frequently silenced in multiple common tumors.

The critical 8p22 tumor suppressor deleted in liver cancer 1 (DLC1) is frequently inactivated by aberrant CpG methylation and/or genetic deletion and implicated in tumorigeneses of multiple tumor types. Here, we report the identification and characterization of its new isoform, DLC1 isoform 4 (DLC1-i4). This novel isoform encodes an 1125-aa (amino acid) protein with distinct N-terminus as compared with other known DLC1 isoforms. Similar to other isoforms, DLC1-i4 is expressed ubiquitously in normal tissues and immortalized normal epithelial cells, suggesting a role as a major DLC1 transcript. However, differential expression of the four DLC1 isoforms is found in tumor cell lines: Isoform 1 (longest) and 3 (short thus probably nonfunctional) share a promoter and are silenced in almost all cancer and immortalized cell lines, whereas isoform 2 and 4 utilize different promoters and are frequently downregulated. DLC1-i4 is significantly downregulated in multiple carcinoma cell lines, including 2/4 nasopharyngeal, 8/16 (50%) esophageal, 4/16 (25%) gastric, 6/9 (67%) breast, 3/4 colorectal, 4/4 cervical and 2/8(25%) lung carcinoma cell lines. The functional DLC1-i4 promoter is within a CpG island and is activated by wild-type p53. CpG methylation of the DLC1-i4 promoter is associated with its silencing in tumor cells and was detected in 38-100% of multiple primary tumors. Treatment with 5-aza-2'-deoxycytidine or genetic double knockout of DNMT1 and DNMT3B led to demethylation of the promoter and reactivation of its expression, indicating a predominantly epigenetic mechanism of silencing. Ectopic expression of DLC1-i4 in silenced tumor cells strongly inhibited their growth and colony formation. Thus, we identified a new isoform of DLC1 with tumor suppressive function. The differential expression of various DLC1 isoforms suggests interplay in modulating the complex activities of DLC1 during carcinogenesis.

Penile strangulation: report of two unusual cases.

We report two cases of penile strangulation that presented to our emergency department. In the first case, a 60-year-old man, the object of strangulation was a metallic ring that was extricated using an orthopaedic cutter in the operating theatre. The patient recovered uneventfully. In the second case, a 77-year-old man, the object of strangulation was a plastic bottle, which was extricated using surgical instruments in the emergency department, but the patient subsequently developed postobstructive diuresis. The first case illustrates the difficulty that may be encountered in this delicate yet urgent situation, while the second case reports a rare complication.

Foetal rhabdomyoma with fine-needle aspirate cytology correlation.

A case of intermediate form of foetal rhabdomyoma with cytological correlation is reported in a ten-year-old girl who presented with a lump in the right neck region. Fine-needle aspirate of the lump was performed. Cytological findings were that of spindled cells and rhabdomyoblasts with abundant eosinophilic cytoplasm. The lesion was subsequently excised. Histology showed a well-circumscribed cellular lesion composed of oval- to spindle-shaped cells. There were interspersed immature skeletal muscle cells with uniform nuclei and eosinophilic tapered cytoplasm and ganglion-like rhabdomyoblasts. No marked cellular atypia or prominent mitoses was noted. Immunohistochemically, the tumour cells showed positivity for muscle specific actin, myoglobin and myogenin. There was focal positivity for desmin. The patient showed no evidence of local recurrence or metastasis after a 32-month follow-up. This is believed to be the first case report of cytological findings in an intermediate form of foetal rhabdomyoma.