Ambulance use affects timely emergency treatment of acute ischaemic stroke.

INTRODUCTION: For acute ischaemic stroke patients, treatment with intravenous tissue plasminogen activator within a 4.5-hour therapeutic window is essential. We aimed to assess the time delays experienced by stroke patients arriving at the emergency department and to compare ambulance users and non-ambulance users. METHODS: We performed a prospective cohort study in a tertiary hospital in Hong Kong. All acute stroke patients attending the emergency department from January to June 2017 were recruited. Patients who were in hospital at the time of stroke onset and those who transferred from other hospitals were excluded. Three phases were compared between ambulance users and non-ambulance users: phase I, between stroke onset and calling for help; phase II, between calling for help and arriving at the emergency department; and phase III, between arriving and receiving medical assessment. RESULTS: Of 102 consecutive patients recruited, 48 (47%) patients arrived at the emergency department by ambulance. The percentage of stroke patients attending emergency department within the therapeutic window was significantly higher for ambulance users than for non-ambulance users (64.6% vs 29.6%; P<0.001). For phases I, II and III, the median times were significantly shorter for ambulance users (77.5, 32 and 8 min, respectively) than for non-ambulance users (720, 44.5 and 15 min, respectively; all P<0.001). CONCLUSION: Transport of patients to the emergency department by ambulance is important for timely and effective stroke treatment.

Vitamin B12 deficiency in the institutionalized elderly: A regional study.

The prevalence of vitamin B12 deficiency increases with age and is suggested to be even higher in the elderly living in institutions. This retrospective study evaluated the vitamin B12 and folate status of 1996 institutionalized elderly residents aged over 65years. Among them, 34.9% had vitamin B12 deficiency (serum vitamin B12 <150pmol/L), 11.8% had folate deficiency (serum folate <6.8nmol/L), and 4.9% had both. The majority of vitamin B12 deficient residents (68%) had serum vitamin B12 between 100pmol/L and 149pmol/L. Macrocytosis was found in 24.2% of vitamin B12 deficient residents. A significant increase in macrocytosis was associated with a decrease in serum vitamin B12 below 100pmol/L. Macrocytosis was most common in those with vitamin B12 ≦69pmol/L (50.9%). Overall, vitamin B12 deficiency is common in the institutionalized elderly, however macrocytosis cannot predict deficiency. More liberal testing for vitamin B12 status in the institutionalized elderly may be warranted.

An expedited stroke triage pathway: the key to shortening the door-to-needle time in delivery of thrombolysis.

OBJECTIVES: To assess time management of stroke thrombolysis triage and functional outcomes in patients receiving recombinant tissue plasminogen activator for hyperacute stroke, and identify bottlenecks in delivery of the treatment. DESIGN: Prospective study. SETTING: A university teaching hospital in Hong Kong. PATIENTS: Patients with suspected hyperacute stroke referred to the stroke thrombolysis team during October 2008 to September 2009. MAIN OUTCOME MEASURES: Time performance records including door-to-stroke team, door-to-needle, and onset-to-thrombolysis times. Functional outcomes by modified Rankin Scale score at 3 months, and thrombolysis-related complications including haemorrhagic transformations and mortality. RESULTS: During the 12-month period, 95 thrombolysis calls were received; recombinant tissue plasminogen activator was given intravenously to 17 (18%) of the patients and intra-arterially to 11 (12%). The mean (standard deviation) door-to-stroke team and the door-to-needle times for intravenous recombinant tissue plasminogen activator patients were 33 (25) and 80 (25) minutes, respectively; both were about 20 minutes longer than that recommended by the National Institute of Neurological Disorders and Stroke. The mean National Institute of Health Stroke Scale score for patients received intravenous recombinant tissue plasminogen activator was 16 (standard deviation, 7). The mean (standard deviation) onset-to-treatment time was 144 (42) minutes. Nine (53%) patients who received intravenous recombinant tissue plasminogen activator achieved favourable outcomes at 3 months, with a modified Rankin Scale score of 0 to 1. Symptomatic haemorrhage and mortality occurred in one (6%) patient. CONCLUSION: A dedicated stroke triage pathway is essential to ensure efficient and safe delivery of thrombolysis therapy. Improvements in door-to-stroke team time through integration with emergency medicine staff and neuroradiologists may improve thrombolysis eligibility.

Low-dose 5-fluorouracil induces cell cycle G2 arrest and apoptosis in keloid fibroblasts.

BACKGROUND: Intralesional injection of low-dose 5-fluorouracil (5-FU) has recently been used as an experimental modality for treating keloid scarring and has shown promising efficacy in improving scar appearance and preventing recurrence of the keloid. OBJECTIVES: We sought to explore the cellular- and molecular-based evidence for the observed clinical benefits. METHODS: Primary cell lines of keloid fibroblasts were treated with 5-FU at a range of lower doses (∼10 mg mL(-1) ) in monolayer culture and subjected to examination for cell viability, proliferative potential, apoptosis, cell cycle and associated proteins involved in cell cycle control. RESULTS: 5-FU significantly inhibited cell proliferation of keloid fibroblasts in the full dose range used in this study. The DNA synthesis was completely inhibited by 5-FU at 72 h, and significant cell apoptosis was observed at concentrations ≥ 1 mg mL(-1) for a period over 72 h. 5-FU caused a significant delay in cell cycle progression and the G2/M phase arrest. 5-FU induced p53 and p21 accumulation together with a decrease in cyclin B1 and Bcl-2 levels in treated keloid fibroblasts. CONCLUSIONS: Our data indicate that low-dose 5-FU (as low as 1 mg mL(-1) ) induces significant inhibition of proliferation, G2/M cell cycle arrest and apoptosis but not immediate cell death of keloid fibroblasts. The lack of tissue necrosis is a particular benefit as further scarring is likely to be prevented. These results support the use of low-dose 5-FU as a potential modality for treating keloid scars.

Molecular detection of a novel human influenza (H1N1) of pandemic potential by conventional and real-time quantitative RT-PCR assays.

BACKGROUND: Influenza A viruses are medically important viral pathogens that cause significant mortality and morbidity throughout the world. The recent emergence of a novel human influenza A virus (H1N1) poses a serious health threat. Molecular tests for rapid detection of this virus are urgently needed. METHODS: We developed a conventional 1-step RT-PCR assay and a 1-step quantitative real-time RT-PCR assay to detect the novel H1N1 virus, but not the seasonal H1N1 viruses. We also developed an additional real-time RT-PCR that can discriminate the novel H1N1 from other swine and human H1 subtype viruses. RESULTS: All of the assays had detection limits for the positive control in the range of 1.0 x 10(-4) to 2.0 x 10(-3) of the median tissue culture infective dose. Assay specificities were high, and for the conventional and real-time assays, all negative control samples were negative, including 7 human seasonal H1N1 viruses, 1 human H2N2 virus, 2 human seasonal H3N2 viruses, 1 human H5N1 virus, 7 avian influenza viruses (HA subtypes 4, 5, 7, 8, 9, and 10), and 48 nasopharyngeal aspirates (NPAs) from patients with noninfluenza respiratory diseases; for the assay that discriminates the novel H1N1 from other swine and human H1 subtype viruses, all negative controls were also negative, including 20 control NPAs, 2 seasonal human H1N1 viruses, 2 seasonal human H3N2 viruses, and 2 human H5N1 viruses. CONCLUSIONS: These assays appear useful for the rapid diagnosis of cases with the novel H1N1 virus, thereby allowing better pandemic preparedness.

Bicycle related injuries presenting to a trauma centre in Hong Kong.

BACKGROUND: Bicycle riding is a popular leisure activity and an important means of transportation in Hong Kong. Young cyclists' riding behaviour causes injury patterns which may differ from older riders. The aim of this study is firstly to describe bicycle related injuries presenting to a regional trauma centre in Hong Kong, and secondly to compare patients aged > 15 years with those patients aged < or = 15 years. METHODS: This retrospective observational study examined all bicycle related injury patients presenting to the ED of the Prince of Wales Hospital (PWH) in 2006. RESULTS: Results showed that bicycle helmet use was low in Hong Kong suggesting that the wearing of helmets when cycling should be promoted. Bicycle related injuries were common in children but the injuries in adults were more serious. Head and limb injuries were common and limbs on the left side were 2.5 times more likely to be injured than those on the right. The older group were more likely to be involved in a motor vehicle collision and sustained more severe injuries than the younger group. They had more serious head and neck, face, thorax and abdominal injuries compared to the younger group. CONCLUSION: Prevention strategies should include more widespread helmet use and increasing bicycle lane provision to enable traffic separation in Hong Kong. The three 'E' approaches (education, enforcement and environment) should be implemented to prevent bicycle injuries in Hong Kong.

Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.

BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.

Antithrombotic treatment of atrial fibrillation in a regional hospital in Hong Kong.

OBJECTIVE: To measure the use, appropriateness, and safety of antithrombotic therapy in Hong Kong Chinese patients with atrial fibrillation. DESIGN: Retrospective review. SETTING: Regional hospital, Hong Kong. SUBJECTS AND METHODS: Medical records of all patients with atrial fibrillation admitted to acute internal medicine wards in April 2000 and between July and October 2001 were reviewed for details of antithrombotics given, results of international normalised ratio monitoring for patients receiving warfarin, side-effects, and additional risk factors for complications of atrial fibrillation. Statistical analysis was undertaken to assess factors predictive of antithrombotic use. RESULTS: A total of 207 patients with chronic atrial fibrillation were included in the study. Of these, 44.0% of patients with non-valvular atrial fibrillation without contra-indications for warfarin use were receiving warfarin, 34.1% were receiving aspirin, and 22.0% were receiving no antithrombotic therapy. The majority of patients (69.1%) were treated appropriately according to the American College of Chest Physicians guidelines. The major side-effect rates for warfarin and aspirin were 2.14% and 1.72% per patient-year, respectively, which were comparable with western studies of usual clinical practice. The ischaemic stroke rate for patients taking warfarin or aspirin were 1.40% and 6.02% per patient-year, respectively. The median international normalised ratio was 1.96. The median frequency of international normalised ratio measurement was 45.58 days. CONCLUSIONS: This study found that antithrombotic use in a Hong Kong regional hospital for patients with atrial fibrillation was similar to that reported from western institutions. Complication and stroke rates were also comparable to the western data relating to usual clinical practice.

A new method for improving metaphase chromosome spreading.

BACKGROUND: The success of complex molecular cytogenetic studies depends on having properly spread chromosomes. However, inconsistency of optimum chromosome spreading remains a major problem in cytogenetic studies. METHODS: The metaphase spreading process was carefully timed to identify the most critical phase of chromosome spreading. The effects of dropping height of cell suspension, slide condition, drying time, fixative ratio, and relative humidity on the quality of metaphase spreads were studied by quantitative examination of metaphase chromosome spreads. Normal and immortalized human epithelial ovarian cells, neuroblastoma cells, and normal lymphocytes were tested. RESULTS: Humidity over the slide was the most important variable affecting the quality of chromosome spreads. Consistent improvement in chromosome spreading (larger metaphase area, less chromosome overlaps, or lower frequencies of broken metaphases) was obtained for all cell types if dynamic cell rehydration, occurring as fixative absorbs moisture from air, was made to coincide with the prompt fixation of spread chromosomes to the slide. This was achieved by dropping cells on dry glass slides placed in a shallow metal tray and then quickly lowering the tray into a covered 50 degrees C water bath for slide drying. CONCLUSIONS: A new and simple method for improving metaphase chromosome spreading was developed based on our study on the characteristics of chromosome spreading.

A retrospective review of transcatheter hepatic arterial embolisation for ruptured hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a disease with a high prevalence in South East Asia. It is not uncommon to encounter rupture of the tumour in an emergency situation. Operative measures in this situation are often associated with high mortality rates. Transcatheter arterial embolisation (TAE) appears to be an effective alternative to surgery and is increasingly used by many centres. In this study, we have reviewed the outcome of our patients after receiving TAE and tried to identify prognostic indicator(s). PATIENTS AND METHODS: From 1996 to 2000, we had retrospectively reviewed the outcome of 31 patients who had undergone TAE for rupture of HCC and compared their survival with respect to different prognostic indicators. RESULTS: The were 31 patients with a mean age of 53 years. At the time of rupture, 19 patients had Child's A, 5 Child's B and 7 of Child's C disease. The most common presentation was abdominal pain (14 patients). Bleeding was successfully arrested in all 31 patients. The most common complication was fever (13 patients). The overall mean survival was 126 days. Eight patients died within 30 days of admission, the major cause of death was liver failure, which occurred in 6 patients. In addition, we had also postulated several prognostic indicators for patients' survival. The results showed that only those with a bilirubin level below 50 umol/L and who presented with shock had a poor outcome. CONCLUSION: TAE should be considered in the initial management of patients with ruptured HCC. It is effective in arresting tumour bleeding and allows the patient to have subsequent definitive management.

A pruning method for the recursive least squared algorithm.

The recursive least squared (RLS) algorithm is an effective online training method for neural networks. However, its conjunctions with weight decay and pruning have not been well studied. This paper elucidates how generalization ability can be improved by selecting an appropriate initial value of the error covariance matrix in the RLS algorithm. Moreover, how the pruning of neural networks can be benefited by using the final value of the error covariance matrix will also be investigated. Our study found that the RLS algorithm is implicitly a weight decay method, where the weight decay effect is controlled by the initial value of the error covariance matrix; and that the inverse of the error covariance matrix is approximately equal to the Hessian matrix of the network being trained. We propose that neural networks are first trained by the RLS algorithm and then some unimportant weights are removed based on the approximate Hessian matrix. Simulation results show that our approach is an effective training and pruning method for neural networks.

Two regularizers for recursive least squared algorithms in feedforward multilayered neural networks.

Recursive least squares (RLS)-based algorithms are a class of fast online training algorithms for feedforward multilayered neural networks (FMNNs). Though the standard RLS algorithm has an implicit weight decay term in its energy function, the weight decay effect decreases linearly as the number of learning epochs increases, thus rendering a diminishing weight decay effect as training progresses. In this paper, we derive two modified RLS algorithms to tackle this problem. In the first algorithm, namely, the true weight decay RLS (TWDRLS) algorithm, we consider a modified energy function whereby the weight decay effect remains constant, irrespective of the number of learning epochs. The second version, the input perturbation RLS (IPRLS) algorithm, is derived by requiring robustness in its prediction performance to input perturbations. Simulation results show that both algorithms improve the generalization capability of the trained network.

Difference in susceptibilities of different cell lines to bilirubin damage.

OBJECTIVE: To investigate if there are differences in susceptibilities to bilirubin toxicity of different cell lines. METHODOLOGY: A modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method was adopted to study the cytotoxic effect of bilirubin on several commercially available cell lines including human glioblastoma (ATCC CRL 1690, T98G), human neuroblastoma (ATCC HTB-10, SK-N-MC), human liver (ATCC CCL 13, Chang Liver, HeLa markers) and a mouse fibroblast (ATCC CCL-1, NCTC Colon 929). RESULTS: Cytotoxicity was observed when certain bilirubin:albumin molar ratios were exceeded in the medium of a cell line in culture. Different cells exhibited different susceptibilities to the cytotoxic effects of bilirubin; neuroblastoma and glioblastoma were most susceptible, fibroblasts were the least vulnerable. CONCLUSIONS: Our findings have confirmed the clinical impression that different cells sustain different degrees of cytotoxicities caused by bilirubin.

A local training and pruning approach for neural networks.

The training of neural networks using the extended Kalman filter (EKF) algorithm is plagued by the drawback of high computational complexity and storage requirement that may become prohibitive even for networks of moderate size. In this paper, we present a local EKF training and pruning approach that can solve this problem. In particular, the by-products obtained along with the local EKF training can be utilized to measure the importance of the network weights. Comparing with the original global approach, the proposed local EKF training and pruning approach results in a much lower computational complexity and storage requirement. Hence, it is more practical in solving real world problems. The performance of the proposed algorithm is demonstrated on one medium- and one large-scale problems, namely, sunspot data prediction and handwritten digit recognition.

An adaptive Bayesian pruning for neural networks in a non-stationary environment.

Pruning a neural network to a reasonable smaller size, and if possible to give a better generalization, has long been investigated. Conventionally the common technique of pruning is based on considering error sensitivity measure, and the nature of the problem being solved is usually stationary. In this article, we present an adaptive pruning algorithm for use in a nonstationary environment. The idea relies on the use of the extended Kalman filter (EKF) training method. Since EKF is a recursive Bayesian algorithm, we define a weight-importance measure in term of the sensitivity of a posteriori probability. Making use of this new measure and the adaptive nature of EKF, we devise an adaptive pruning algorithm called adaptive Bayesian pruning. Simulation results indicate that in a noisy nonstationary environment, the proposed pruning algorithm is able to remove network redundancy adaptively and yet preserve the same generalization ability.

Detection of p53 mutations in Hong Kong colorectal carcinomas by conventional PCR-SSCP analysis versus p53 yeast functional assays.

BACKGROUND: Previous reports indicate that the p53 yeast functional assay is a highly sensitive method of detection of p53 mutations in clinical specimens. Our earlier report (1) showed a 35.4% p53 mutation frequency in Hong Kong colorectal carcinoma (CRC) patients, when conventional molecular screening techniques were utilized to assess the mutation rate in the hot spots in exons 5-8. MATERIALS AND METHODS: The yeast functional assay was used to determine if the previous mutation frequency determined by PCR-SSCP techniques was under-estimated, and if so, to see if other hot spots for mutations explain this difference. RESULTS: The p53 functional yeast assay results showed an increased mutation frequency. However, sequencing showed the mutations were confined to common hot spots for mutations in exons 6 and 7. CONCLUSIONS: The mutation frequency in CRC patients observed with the yeast assay is higher than previously reported. Forty-five percent of 20 SSCP-negative specimens were positive by the yeast assay, which this study shows is superior for detection of p53 mutations directly in clinical specimens containing varying amounts of normal tissue contamination.

Comparative p53 mutational spectra in aerodigestive tract tumors in Hong Kong Chinese patients.

The p53 mutations in colorectal, esophageal and lung carcinomas from Hong Kong were studied previously. The availability of mutation data for these cancers in one geographical region prompted investigations into special features of these p53 alterations. Mutations in codons 175, 176, 248 and 273 accounted for 35% of all mutations detected. A hot spot at codon 176 observed in esophageal carcinomas was not detected in any of the other aerodigestive tract tumors studied and appeared to be uniquely restricted to Chinese esophageal cancers. Other unique mutation sites, and a notably higher frequency of insertions and deletions in each of these cancers, were also detected in Chinese patients as compared to Caucasians.

Analysis for a class of winner-take-all model.

Recently we have proposed a simple circuit of winner-take-all (WTA) neural network. Assuming no external input, we have derived an analytic equation for its network response time. In this paper, we further analyze the network response time for a class of winner-take-all circuits involving self-decay and show that the network response time of such a class of WTA is the same as that of the simple WTA model.