Impact of a novel pre-hospital stroke notification programme on acute stroke care key performance indicators in Hong Kong: a multicentre prospective cohort study with historical controls.

INTRODUCTION: Early identification and initiation of reperfusion therapy is essential for suspected acute ischaemic stroke. A pre-hospital stroke notification (PSN) protocol using FASE (facial drooping, arm weakness, speech difficulties, and eye palsy) was implemented to improve key performance indicators (KPIs) in acute stroke care delivery. We assessed KPIs and clinical outcomes before and after PSN implementation in Hong Kong. METHODS: This prospective cohort study with historical controls was conducted in the Accident and Emergency Departments of four public hospitals in Hong Kong. Patients were screened using the PSN protocol between August 2021 and February 2022. Suspected stroke patients between August 2020 and February 2021 were included as historical controls. Door-to-needle (DTN) and door-to-computed tomography (DTC) times before and after PSN implementation were compared. Clinical outcomes including National Institutes of Health Stroke Scale score at 24 hours and modified Rankin Scale score at 3 months after intravenous recombinant tissue-type plasminogen activator (IV-rtPA) were also assessed. RESULTS: Among the 715 patients (266 PSN and 449 non-PSN) included, 50.8% of PSN patients and 37.7% of non-PSN patients had a DTC time within 25 minutes (P<0.001). For the 58 PSN and 134 non-PSN patients given IV-rtPA, median DTN times were 67 and 75.5 minutes, respectively (P=0.007). The percentage of patients with a DTN time within 60 minutes was higher in the PSN group than in the non-PSN group (37.9% vs 21.6%; P=0.019). No statistically significant differences in clinical outcomes were observed. CONCLUSION: Although the PSN protocol shortened DTC and DTN times, clinical outcomes did not significantly differ.

Atrial fibrillation patients who sustained warfarin-associated intracerebral haemorrhage have poor neurological outcomes: results from a matched case series.

INTRODUCTION: Coagulopathy-associated intracerebral haemorrhage has become increasingly common because of the rising demand in the ageing population for anticoagulation for atrial fibrillation. This study compared the clinical features and neurological outcomes of intracerebral haemorrhage in patients with atrial fibrillation who were prescribed warfarin with those who were not. METHODS: This was a retrospective matched case series of patients with intracerebral haemorrhage from three tertiary hospitals in Hong Kong from 1 January 2006 to 31 December 2011. Patients who developed intracerebral haemorrhage and who were prescribed warfarin for atrial fibrillation (ICH-W group) were compared with those with intracerebral haemorrhage and not prescribed warfarin (ICH-C group); they were matched for age and gender in 1:1 ratio. Clinical features and neurological outcomes were compared, and the impact of coagulopathy on haematoma size was also studied. RESULTS: We identified 114 patients in the ICH-W group with a mean age of 75 years. Both ICH-W and ICH-C groups had a median intracerebral haemorrhage score of 2. There was a non-statistically significant trend of higher intracerebral haemorrhage volume in the ICH-W group (12.9 mL vs 10.5 mL). The median modified Rankin Scale and the proportion with good recovery (modified Rankin Scale score ≤3) at 6 months were comparable. Nonetheless, ICH-W patients had higher hospital mortality (51.8% vs 36.0%; P=0.02) and 6-month mortality (60.5% vs 43.0%; P=0.01) than ICH-C patients. Overall, 60% of ICH-W patients had their admission international normalised ratio within the therapeutic range during intracerebral haemorrhage, and 14% had a subtherapeutic admission international normalised ratio. International normalised ratio at admission was not associated with intracerebral haemorrhage volume or neurological outcome. CONCLUSION: Warfarin-associated intracerebral haemorrhage in patients with atrial fibrillation carried a higher stroke mortality than the non-warfarinised patients.

Prevalence of GB virus type C viraemia in MSM with or without HIV-1 infection in Beijing, China.

GB virus C (GBV-C) is frequently identified in patients co-infected with human immunodeficiency virus type 1 (HIV-1) due to the similar transmission routes. However, it remains unclear how these two viruses interact with each other and how one virus affects the replication of the other in the human body. In this study, we performed a case-control study to determine whether GBV-C viraemia could prevent the acquisition of HIV-1 infection, and a cohort study to determine the prevalence, genotypic characteristics and incidence of GBV-C infection in men who have sex with men (MSM) populations in Beijing, China. The prevalence of GBV-C infection in HIV-1-negative subjects was similar to that in HIV-1-positive subjects. Before HIV-1 acquisition, the prevalence of GBV-C was 17·7%, which increased to 27·2% at the acute stage and to 34% at the chronic stage. Genotype 3 was the major genotype of GBV-C in both groups. A significantly positive correlation was observed between the CD4+ T-cell counts and GBV-C viral loads at the acute stage of HIV infection. At the chronic stage (12 months later), this correlation was no longer significant, although it was still positive. Overall, this study demonstrated that pre-existing GBV-C viraemia could not prevent the acquisition of HIV-1 infection and transmission of HIV-1 significantly increased the prevalence of GBV-C viraemia.

Deriving the aquatic predicted no-effect concentrations (PNECs) of three chlorophenols for the Taihu Lake, China.

The Predicted No-Effect Concentration (PNEC) is a key for ecological risk assessment. In this paper, the aquatic species existing widely in the Taihu Lake were selected, and their toxicity data to 2,4-dichlorophenol (2,4-DCP), 2,4,6-trichlorophenol (2,4,6-TCP) and pentachlorophenol (PCP) were collected. The PNECs of 2,4-DCP; 2,4,6-TCP; and PCP were derived using three different approaches, i.e., the assessment factor (AF), species sensitivity distribution (SSD) as well as an eco-toxicological model (AQUATOX). As the results, PNEC(AF)s were 2.18 µg L(-1), 2.53 µg L(-1) and 0.26 µg L(-1), and PNEC(SSD)s were 77 µg L(-1), 197 µg L(-1) and 10 µg L(-1), respectively for 2,4-DCP; 2,4,6-TCP; and PCP respectively. Based on the aquatic conditions of the Taihu Lake, the derived site-specific PNEC(AQUATOX)s were 15 µg L(-1), 67 µg L(-1) and 4 µg L(-1), respectively. In general, the PNECs for three chlorophenols derived from different approaches followed the declined order of PNEC(SSD) > PNEC(AQUATOX) > PNEC(AF). The ratios of PNEC(AF) to PNEC(SSD) and PNEC(AQUATOX) to PNEC(SSD) for three chlorophenols were 0.013-0.028 and 0.19-0.4, respectively. It indicated that PNECs obtained using different approaches may vary and the one based on the AF was the lowest. Therefore, PNEC(AF) can be seen as overprotective. The PNEC(AQUATOX) values for three chlorophenols were less than the corresponding PNEC(SSD) values, mostly because the indirect effects were considered in the ecological model.

Association of long non-coding RNA H19 and microRNA-21 expression with the biological features and prognosis of non-small cell lung cancer.

In recent years, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been shown to play important roles in tumor biological function. The aim of this study was to investigate the diagnostic and prognostic value of lncRNA H19 and miR-21 expression in non-small-cell lung cancer (NSCLC). H19 and miR-21 expression was measured in tumor tissues and corresponding non-tumor lung tissues from 200 patients by quantitative reverse transcription polymerase chain reaction. Moreover, the in vitro and in vivo effects of H19 knock out in A549 cells were investigated. Expression of both H19 and miR-21 was significantly higher in lung tissues from patients with NSCLC than in normal lung tissues. Increased expression of H19 and miR-21 was positively correlated with advanced tumor-node-metastasis stage and tumor size. miR-21 expression was highest in stage I and II NSCLC, whereas H19 expression was highest in stage III and IV NSCLC. Knockout of H19 significantly inhibited NSCLC cell proliferation both in vitro and in vivo. The results show that H19 may mainly contributes to the progression of NSCLC, and its expression levels can reflect the invasive and metastatic status to some extent. miR-21 expression more likely plays an important role in early stage NSCLC. Moreover, H19 and miR-21 interact in the regulation of NSCLC, and with greater expression of both H19 and miR-21, overall survival decreased. The combination of H19 and miR-21 may have diagnostic value in NSCLC and represent a target for new NSCLC treatments.

MiR-146a-5p level in serum exosomes predicts therapeutic effect of cisplatin in non-small cell lung cancer.

OBJECTIVE: Lung cancer is the most common cause of death in cancer worldwide, and cisplatin plays an important role in its treatment. However, the response to chemotherapy is poorly attributable to drug resistance. Our present study aimed to investigate the relation of the exosomal miR-146a-5p level with the chemosensitivity of NSCLC to cisplatin and the molecular mechanism that miR-146a-5p mediated to effect on chemotherapy response. PATIENTS AND METHODS: The exosomes were isolated by ExoQuick kit. The exosomal morphology and particle size distribution were evaluated by the transmission electron microscopy and nanoSight assay respectively. Cell proliferation was detected using the MTT assay. NSCLC cells were infected with mimics or inhibitor to overexpress or downregulate miR-146a level. Besides, Quantitative real-time PCR, Western blot analysis, and immunohistochemistry were applied to detect the relative miRNA and protein levels. RESULTS: Advanced NSCLC patients with low serum exosomal miR-146a-5p levels had higher recurrence rates than those with high levels. A549/DDP cells and exosomes expressed higher miR-146a-5p than A549. In the process of cisplatin-induced drug resistance, the expression of miR-146a-5p decreased in either NSCLC cell lines or the exosomes gradually. What's more, the overexpression of miR-146a-5p could reverse the resistance of A549/DDP. And the possible mechanism of miR-146a-5p increasing chemosensitivity of NSCLC to cisplatin could be targeting Atg12 to inhibit autophagy. CONCLUSIONS: Serum exosomal miR-146a-5p may be a new biomarker predicting the efficacy of cisplatin for NSCLC patients and real-time monitoring drug resistance.

Obesity inversely correlates with prostate-specific antigen levels in a population with normal screening results of prostate cancer in northwestern China.

Serum prostate-specific antigen (PSA) is a diagnostic biomarker of prostate cancer and is possibly associated with obesity. This study aimed to explore the relationships between obesity indicators [body mass index (BMI) and waist circumference (WC)] with PSA in Chinese men. A cross-sectional study of men aged 30-85 years undergoing prostate cancer screening was conducted from August 2008 to July 2013 in Xi'an, China. Data were obtained from clinical reports, condition was recorded based on self-report including demographics, weight, height, and WC (>90 cm=obese). Fasting blood glucose (FBG) and prostate volume (PV) were assessed clinically. Patients were grouped by BMI (normal=22.9, overweight=23-27.4, obese≥27.5 kg/m2). PSA parameters of density (PSAD), PSA serum level, and PSA increasing rate per year (PSAR) were calculated per BMI and age groups (30-40, 41-59, 60-85 years). Obesity indicators (BMI and WC) and PSA parameter relationships were modeled by age-stratified linear regression. Of 35,632 Chinese men surveyed, 13,084 were analyzed, including 13.44% obese, 57.44% overweight, and 29.12% normal weight, according to BMI; 25.84% were centrally (abdominally) obese according to WC. BMI and WC were negatively associated with all PSA parameters, except PSAD and PSAR [P<0.05, BMI: ß=-0.081 (95%CI=-0.055 to -0.036), WC: ß=-0.101 (-0.021 to -0.015)], and independent of FBG and PV (P<0.05) in an age-adjusted model. In conclusion, obesity was associated with lower PSA in Chinese men. Therefore, an individual's BMI and WC should be considered when PSA is used to screen for prostate cancer.

A registry of tuberculous meningitis in Hong Kong.

BACKGROUND: A prospective observational study of the presentation, diagnosis, treatment and outcome of tuberculous meningitis (TBM). METHODS: Demographic characteristics, clinical information, treatment and progress of TBM patients were followed. Their outcomes were ascertained every 6 months for 3 years after diagnosis. Prognostic factors associated with death or full recovery were examined using multivariate Cox's and logistic regression models, respectively. RESULTS: Between 1993 and 2000, 166 TBM patients were recruited. Their mean age was 42.9, 153 were Chinese and 81 were males; 92% received HRZS (H = isoniazid; R = rifampicin; Z = pyrazinamide; S = streptomycin), HRZE (E = ethambutol) or HRZES. Steroids were given to 105 patients, with no significant effect on outcome. After 3 years of follow-up, 110 patients had completely recovered, 20 survived with disability and 26 died. Death was significantly associated with older age, lower cerebrospinal fluid (CSF) lymphocyte and poorer consciousness levels at the time of presentation, while full recovery was associated with younger age, being female and absence of complications. CONCLUSIONS: Relatively good outcomes of TBM cases were documented in this Hong Kong study with a case-fatality ratio of 15.7% (26/166) up to 3 years. Early recognition, diagnosis and administration of effective treatment regimens were probably the most important factors in reducing mortality and morbidity.

Spinocerebellar ataxia type 6.

We report a 39-year-old woman with spinocerebellar ataxia type 6. She presented with ataxia and a 3-year history of progressive ataxia and recurrent falls. There was no relevant family history. Genetic tests revealed an expanded allele of 24 CAG repeats at the spinocerebellar ataxia type 6 locus. This appears to be the first case reported in Hong Kong. As genetic testing becomes more widely available and clinical awareness increases, more such patients are expected to be diagnosed.

Pathways involved in the spread of buccal carcinoma on contrast-enhanced multislice CT.

OBJECTIVES: To explore how buccal carcinoma spread, using contrast-enhanced multislice CT (CEMSCT). METHODS: We retrospectively analysed the extent of lesions in 56 patients with primary buccal squamous cell carcinoma (SCCA). Abnormal manifestations on CEMSCT at oral subsites and involved adjacent structures were documented and evaluated, which were compared with the results of surgery and histopathology. RESULTS: Infiltration and spread to oral subsites and/or adjacent structures was confirmed in 33 patients (58.9%). The opening of the Stensen duct was the most commonly invaded oral subsite (72.7%); other sites included the gingivobuccal sulcus (60.6%), pterygomandibular raphe (54.5%), gingiva (24.2%), retromolar trigone (24.2%), orbicularis oris (18.2%) and the floor of mouth (15.2%). Of the involved adjacent structures, the buccal space was the most common site of spread (69.7%), followed by the masticatory muscles and spaces (57.6%), bone (54.5%), skin and subcutaneous fat (39.4%), pharynx (30.3%), investing fascia (15.2%) and the base of the skull (6.1%). CEMSCT manifestations of the involvement in buccal SCCAs had correlations with pathological findings (p < 0.05). The sensitivities, specificities and accuracies of two radiologists' evaluation on buccal carcinoma involvement were 50.00%, 23.21% and 73.21%; and 51.79%, 32.14% and 83.93%, respectively. CONCLUSIONS: Buccal SCCAs could superficially and deeply spread to multiple oral subsites and/or adjacent structures. CEMSCT could delineate their spread pathways and extents.

Purified donor T cells alone activate transplantation immunity to the male antigen but induce tolerance in combination with Mac-1+ donor cells.

BACKGROUND: In most experimental systems examined, "professional" antigen-presenting cells (APCs), such as dendritic cells, have been found to activate T cells, whereas "nonprofessional" antigen-bearing cells (nonAPC) may induce tolerance. Some recent studies have suggested that nonAPCs may under certain conditions prime a T-cell immune response. We have attempted to separate the roles of transplanted T cells and monocytic/dendritic cells in activating or tolerizing antigen-specific T cells in vivo, by examining the consequences of parenteral exposure to male antigen in anti-male TCR transgenic female mice. METHODS: Qualitative and quantitative changes in the large population of male-reactive transgenic T cells to various male donor cell populations in transgenic female mice were followed after injections of highly purified male lymphoid cells. Changes in male-reactive T cells with time and the long-term outcome of male skin grafts were measured. RESULTS: When a nonAPC population consisting of highly purified male T cells alone was injected intravenously into H-Y antigen-specific TCR transgenic female mice, the number of host transgenic T cells was sustainably increased, and male graft rejection was accelerated. Injection of a combination of purified T cells and purified Mac-l+ cells induced massive and permanent deletion of the host male-reactive T-cell population and permanent graft tolerance. Mac-l+ cells alone gave no appreciable change in responsive T cells or graft rejection times. CONCLUSIONS: The data indicate that highly purified T cells engrafted alone induce rapid sensitization toward the male antigen. They also show that both male donor T cells and a population of male monocytic/ dendritic cells are required to induce peripheral tolerance toward this antigen and that this tolerance is related to permanent peripheral deletion of male-reactive T cells.

All or none peripheral tolerance induction in H-Y antigen-specific TCR transgenic mice.

In in vivo tolerance induction, the dose of tolerogen injected is generally linearly correlated to the length of tolerance induced. Small, medium and large doses are related to no, partial and long-term tolerance, respectively. However, even with injection of substantially large doses of tolerogen, the length of tolerance induced varies over a wide range. Most of the recipients can still reject donor grafts. In this study, it is shown that the linear dose-response can be altered into an all or nothing response in a H-Y antigen-specific TCR transgenic (Tg) mouse model. In thymectomized female Tg mice, injection of 3, 30 and 100 x 10(6) male spleen cells was correlated to no, partial and massive deletion of Tg (alpha T beta T) CD8 cells, respectively. When the thymectomized Tg mice were injected with 9 x 10(6) T cell-enriched (T+) male cells, one half of the recipients showed no deletion of alpha T beta T cells, and in the other half massive deletion occurred. In complete correlation with deletion, all male skin grafts were rejected in the undeleted group as PBS-injected controls, whereas with massive deletion they were indefinitely tolerized. Thus, partial deletion and partial tolerance can be avoided. Injection of 18 x 10(6) male T+ cells induced long-term tolerance in all the recipients. The all or none T cell deletion and long-term tolerance induction has not only significant implications in understanding the mechanism of peripheral tolerance induction, but also in tolerance induction in transplantation, gene therapy and the prevention and treatment of autoimmune diseases.

Histamine H3-receptors inhibit sympathetic neurotransmission in guinea pig myocardium.

The histamine H3 agonist, (R)-alpha-methylhistamine (alpha-MeHA, 10(-10) to 10(-5) M), caused a concentration-dependent inhibition of the sympathetic contractile response to electrical field stimulation of guinea pig isolated atria, but alpha-MeHA did not alter the basal tension or the contraction induced by exogenously applied norepinephrine. Blockade of H1 and H2 histamine receptors, and alpha- and beta-adrenoceptors failed to prevent the inhibitory effect of alpha-MeHA, whereas the specific H3 receptor antagonist, thioperamide, concentration dependently reversed the inhibitory effect of alpha-MeHA. At the concentration of 10(-7) M, which was effective for antagonizing the action of alpha-MeHA, thioperamide did not modify the sympathetic responses facilitated by the beta 2-adrenoceptor agonist, clenbuterol, or attenuated by the alpha 2-adrenoceptor agonist, clonidine. Our results suggest that H3 receptors exist on the cardiac sympathetic terminals, which may modulate adrenergic neurotransmission in guinea pig myocardium.

Characteristics of depressing effect of cycloprotobuxine-A on the maximal velocity of depolarization in myocardium.

The characteristics of the depressing effect of cycloprotobuxine-A on Vmax in isolated guinea pig myocardium were investigated with a standard microelectrode technique. Cycloprotobuxine-A 3-30 mumol/l produced a concentration-dependent decrease in Vmax, associated with a prolongation of the action potential duration. At 3 mumol/l, a small resting block of Vmax, but a pronounced use-dependent block was found. This use-dependent block increased progressively as stimulation frequency increased from 0.5 to 4.0 Hz. The time constant and rate for onset of use-dependent block were 2.0-7.3 s and 0.11-0.25 AP-1 (reciprocal action potential number), respectively. The time constant and half-life for recovery from use-dependent block were 11.8 and 8.1 s. Thus, the kinetics of the depressing effect of cycloprotobuxine-A on Vmax were intermediate. In muscles depolarized by high [K+]0, the resting block was enhanced slightly, while use-dependent block was greatly augmented. These results suggested that cycloprotobuxine-A could have a low affinity for resting Na+ channels but a much higher affinity for activated and/or inactivated Na+ channels, and that the use-, frequency- and voltage-dependent effects of cycloprotobuxine-A on Vmax may play an important role in preventing the development of cardiac arrhythmias.

Kennedy's disease.

Kennedy's disease is an X-linked, neurodegenerative disorder, characterised by lower motor neuron syndrome. This report gives the clinical details of six male patients with Kennedy's disease diagnosed at Princess Margaret Hospital. Three were initially diagnosed with other neurological diseases, with the diagnosis of Kennedy's disease made after genetic testing. This hereditary disease should be considered in male patients with muscle weakness, particularly those with a presentation suggesting atypical motor neuron disease.

Clinical features of hereditary spinocerebellar ataxia diagnosed by molecular genetic analysis.

OBJECTIVE: To assess the frequency and clinical features of different types of hereditary spinocerebellar ataxia in Hong Kong. DESIGN: Cross-sectional study using a questionnaire and clinical examination, with the majority of the information retrospectively collected. SETTING: Three regional hospitals, Hong Kong. PARTICIPANTS: All patients with spinocerebellar ataxia that was confirmed by molecular genetic tests between January 2001 and October 2003. MAIN OUTCOME MEASURES: History, latest physical examination results, clinical investigation results, and genetic profiles. RESULTS: A total of 16 Chinese patients had received diagnoses of spinocerebellar ataxia. These patients had spinocerebellar ataxia type 1 (n=3), spinocerebellar ataxia type 3 (Machado-Joseph disease; n=12), and dentatorubro-pallidoluysian atrophy (n=1). The most common manifestation was ataxia (15/16), followed by pyramidal signs (12/16). Other features such as bulbar dysfunction, ophthalmoplegia, neuropathy, and cognitive impairment were present but variable. CONCLUSIONS: The clinical manifestations of different types of spinocerebellar ataxia overlap, and genetic study is necessary to confirm the diagnosis. The frequency of spinocerebellar ataxia type 3 is greater than that of other types among these Chinese patients. The age of onset of this type may correlate inversely with the number of CAG repeats.

[Protective effects of nicorandil on myocardial mitochondria function during ischemia and reperfusion].

Experiment with recirculating blood perfusion device showed that nicorandil 0.15 mmol/L significantly counteracted the harmful effect of ischemic and reperfused injury on the respiratory function of myocardial mitochondria. The oxidative phosphorylation efficiency (ADP/O) was increased 19% (p less than 0.01), the respiratory control rate(RCR) was also increased 40% (p less than 0.01); while the content of myocardial calcium and Ca/Mg were decreased; and the ischemia and reperfusion-induced increase of myocardial water content was abolished as compared with solvent control. The results indicate that nicorandil has protective effect on myocardial mitochondria function during ischemia and reperfusion, which may be the result of blocking Ca2+ from entering the cell and prevent lipid peroxidation.

[Protective effects of furyl-dihydropyridine I on ischemic myocardium in isolated rabbit hearts].

A recirculating nonpulsatile perfusion circuit was used in isolated rabbit hearts. Furyl-dihydropyridine I (2,6-dimethyl-4-furyl-1,4-dihydropyridine-3, 5-dicarboxylate) 20 mumol/L was shown to inhibit the release of creatine phosphokinase (CPK) and alpha-hydroxybutyrate dehydrogenase (HBD) from myocardium, decrease myocardial calcium and sodium contents by 5.3 +/- 1.1 mumol/g dry weight (P less than 0.01, n = 6) and 1.50 +/- 0.17 mmol/g dry weight (P less than 0.05, n = 6) from 8.3 +/- 1.1 mumol/g dry weight and 1.96 +/- 0.32 mmol/g dry weight respectively. It was also found to reduce coronary resistance and increase coronary flow of the ischemic myocardium, and prevent ischemic arrhythmia, thereby limit myocardial injury during regional ischemia in isolated rabbit hearts.

[Comparison of antiarrhythmic effects of IHC-72 (an iodonium-72), lidocaine and verapamil].

The antiarrhythmic actions of 3,6-dimethylamino-dibenzopyridonium edetate (IHC-72), lidocaine (Lid) and verapamil (Ver) on several models Were compared at equitoxic doses (equal fraction of LD50). The action of IHC-72 against aconitine induced arrhythmia was similar to that of Lid but stronger than that of Ver in anesthetized rats. The effect of IHC-72 on ouabain induced arrhythmia was also similar to that of Lid, but weaker than that of Ver in anesthetized guinea pigs. The activity of IHC-72 to raise electrical ventricular fibrillation thresholds (VFT) was weaker than that of Lid and Ver. The effects of IHC-72 in decreasing the incidence of ventricular premature beat(VP B), ventricular tachycardia (VT), ventricular fibrillation (VF) and shortening the duration of VT yielded by reperfusion were similar to those of Lid anf Ver in vivo.