[Preliminary study on the role and mechanism of IL-6 receptor antagonists in improving post-infarction ventricular arrhythmia].

Objective: To investigate the effect of tocilizumab (TCZ) on ventricular arrhythmias (VAs) after myocardial infarction (MI) in Sprague-Dawley rats and explore its potential mechanism. Methods: The random number table method was used to divide 32 adult male Sprague-Dawley rats into 4 groups: Sham group, TCZ group, MI group and MI+TCZ group, with 8 rats in each group. The MI model was established by ligation of the left anterior descending branch of the coronary artery in the MI and MI+TCZ groups, and only sutured without ligation in the Sham and TCZ groups. TCZ was injected into the left superior cervical ganglion (SCG) of rats in the TCZ and MI+TCZ groups after successful modeling or sham operation, and the same amount of normal saline was injected in the Sham and MI groups. 24 h after successful modeling, ECG of rats in each group was recorded, heart rate variability (HRV, including low frequency power (LF), high frequency power (HF), LF/HF ratio), QT interval, QTc interval were calculated, and left ventricular effective refractory period (ERP) and VA inducibility were measured. Myocardial infarct size and tissue changes were observed with triphenyl tetrazolium chloride staining and HE staining. Real-time PCR analysis was used to detect the messager RNA (mRNA) expression of interleukin-6 (IL-6) and signal transducer and activator of transcription (STAT) 3 in SCG and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in myocardial infarction periphery. The expression of c-fos in SCG was detected by immunofluorescence staining. Results: Compared with Sham group and MI+TCZ group, rats in MI group had higher LF and LF/HF ratio, longer QT interval and QTc interval, more VAs induced, lower HF and shorter ERP (P all<0.05). Triphenyl tetrazolium chloride staining and HE staining showed that rats in the Sham and TCZ groups had normal myocardial tissue structure, those in the MI group had severe myocardial injury, and those in the MI+TCZ group had less myocardial injury than those in the MI group. Real-ime PCR analysis showed that compared with Sham group and MI+TCZ group, mRNA expression levels of IL-6 and STAT3 in SCG of rats in MI group were higher, and mRNA expression level of myocardial Kcnd2 was lower (P all<0.05). Immunofluorescence staining showed that the content of c-fos in SCG of rats in MI group was higher than that of Sham group and MI+TCZ group (P all<0.05). Conclusions: TCZ may reduce neural activity of the SCG after MI by inhibiting the IL-6/STAT3 signaling pathway, thereby alleviating myocardial injury and inhibiting VAs.

New Measurement of

Carbon and oxygen burning reactions, in particular, ^{12}C+^{12}C fusion, are important for the understanding and interpretation of the late phases of stellar evolution as well as the ignition and nucleosynthesis in cataclysmic binary systems such as type Ia supernovae and x-ray superbursts. A new measurement of this reaction has been performed at the University of Notre Dame using particle-γ coincidence techniques with SAND (a silicon detector array) at the high-intensity 5U Pelletron accelerator. New results for ^{12}C+^{12}C fusion at low energies relevant to nuclear astrophysics are reported. They show strong disagreement with a recent measurement using the indirect Trojan Horse method. The impact on the carbon burning process under astrophysical scenarios will be discussed.

Key

Detection of nuclear-decay γ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense γ-ray flux is thought to be annihilation radiation from the ß^{+} decay of ^{18}F, which is destroyed prior to decay by the ^{18}F(p,α)^{15}O reaction. Estimates of ^{18}F production had been uncertain, however, because key near-threshold levels in the compound nucleus, ^{19}Ne, had yet to be identified. We report the first measurement of the ^{19}F(^{3}He,tγ)^{19}Ne reaction, in which the placement of two long-sought 3/2^{+} levels is suggested via triton-γ-γ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of 1.5-17 at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.

Epidemiology and prognostic factors for mycosis fungoides and Sézary syndrome in a multi-ethnic Asian cohort: a 12-year review.

BACKGROUND: Limited information exists regarding survival of Asian patients with mycosis fungoides (MF) and Sézary syndrome (SS). OBJECTIVE: To evaluate the epidemiology, outcome and prognostic factors of these patients. METHODS: A retrospective review of MF/SS cases diagnosed from 2000 to 2011 at a tertiary referral dermatology centre in Singapore was performed. RESULTS: Of 246 patients, 63% were male and the median age at diagnosis was 49 years. 73.2% were Chinese, 12.6% Indian, 6.9% Malay and 7.3% Caucasian. A total of 239 patients (97.2%) had MF and seven had SS. Median follow-up duration was 6.3 years, and median duration of symptoms at diagnosis was 13 months. For patients with MF, the majority had early disease (92.8% stage IA-IIA). 3.8% were stage IIB, 1.7% stage III and 1.7% stage IV. Complete response to treatment occurred in 78.2%, partial response in 9.6%, persistent but non-progressive disease in 10.0% and disease progression in 4.1% of patients. Large cell transformation occurred in 4.1% of patients. Mean overall survival during this study was 12.7 years, with death occurring in 2.5% of patients (all ≥stage IIB at diagnosis). For patients with SS, 71.4% presented with stage IVA disease, 28.6% stage IVB. Complete response to treatment occurred in 14.2%, persistent but non-progressive disease in 28.6% and disease progression in 57.2% of patients. Mean overall survival was 3.3 years within this study, with death occurring in 42.9% of SS patients. Prognostic factors associated with favourable recurrence-free survival were male gender (P = 0.008), early disease stage (T1) at diagnosis (P < 0.001) and absence of maintenance treatment after remission (P = 0.01). CONCLUSION: Compared to Caucasian and East Asian cohorts, MF in South-East Asians was diagnosed at a younger age and associated with lower mortality, largely due to greater prevalence of hypopigmented MF.

ILC2 frequency and activity are inhibited by glucocorticoid treatment via STAT pathway in patients with asthma.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) were closely associated with asthma. However, there were no perspective studies about the effects of glucocorticoid on ILC2s in asthma patients. Our objective was to perform a perspective study and evaluate the ILC2 activity after glucocorticoid therapy in asthma patients. METHODS: The asthma and asthma with allergic rhinitis patients were treated with glucocorticoid for 3 months. The circulating ILC2 levels were evaluated. The effects of glucocorticoid on ILC2s and possible signalling pathways were investigated in vitro. RESULTS: The patients were well-controlled, and the high ILC2 levels were significantly decreased at 1 and 3 months after treatment. Peripheral blood monocytes from allergic patients produced dramatic IL-5, IL-13 and IL-9 in response to IL-25, IL-33 plus IL-2, and glucocorticoid significantly decreased their levels. Moreover, ILC2s were identified to be the predominant source of IL-5, IL-13 and IL-9, and glucocorticoid treatment was able to reverse their high levels. STAT3, STAT5, STAT6, JAK3 and MEK signalling pathways were proved to be involved in regulating ILC2 activity under the glucocorticoid treatment. CONCLUSION: The data suggested that glucocorticoid administration could be effective in treating asthma by regulating ILC2s via MEK/JAK-STAT signalling pathways. This provides a new understanding of glucocorticoid application in regard to allergic diseases.

Structural and functional 3D mapping of skin tumours with non-invasive multispectral optoacoustic tomography.

BACKGROUND: Recent advances in technology have enabled the development of various non-invasive skin imaging tools to aid real-time diagnosis of both benign and malignant skin tumours, minimizing the need for invasive skin biopsy. Multispectral optoacoustic tomography (MSOT) is a recently developed non-invasive imaging tool, which offers the unique capacity for high resolution three dimensional (3D) optical mapping of tissue by further delivering highly specific optical contrast from a depth of several millimetres to centimetres in living tissues. MSOT enables volumetric, spectroscopic differentiation of tissue, both in vivo and in real time, with and without the application of biomarker-specific probes, and is further able of providing spatial maps of skin chromophores, as well as underlying blood vasculature. METHODS: Three patients with suspicious skin tumours consented to have their lesions imaged with MSOT prior to excision. The histological findings and measurements were compared. RESULTS: We demonstrated the first in vivo clinical use of MSOT for 3D reconstruction of skin tumours in three patients with good histological correlation. CONCLUSION: Our findings confirm the potential benefit of the new imaging method in guiding surgical intervention to achieve a more precise excision with better clearance and lower relapse rates. It can also potentially help to shorten the duration of Mohs' micrographic surgery. Further large-scale studies are necessary to ensure correlation between MSOT and histology.

First Direct Measurement of (12)C((12)C,n)(23)Mg at Stellar Energies.

Neutrons produced by the carbon fusion reaction (12)C((12)C,n)(23)Mg play an important role in stellar nucleosynthesis. However, past studies have shown large discrepancies between experimental data and theory, leading to an uncertain cross section extrapolation at astrophysical energies. We present the first direct measurement that extends deep into the astrophysical energy range along with a new and improved extrapolation technique based on experimental data from the mirror reaction (12)C((12)C,p)(23)Na. The new reaction rate has been determined with a well-defined uncertainty that exceeds the precision required by astrophysics models. Using our constrained rate, we find that (12)C((12)C,n)(23)Mg is crucial to the production of Na and Al in pop-III pair instability supernovae. It also plays a nonnegligible role in the production of weak s-process elements, as well as in the production of the important galactic γ-ray emitter (60)Fe.

Dermatofibrosarcoma protuberans: 35 patients treated with Mohs micrographic surgery using paraffin sections.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) has conventionally been treated with wide local excision. More recently Mohs micrographic surgery (MMS) has been advocated. OBJECTIVES: To assess our departmental experience with DFSP in the context of a literature review relating to DFSP treated with MMS. METHODS: This was a case review of 35 patients with DFSP treated between 1998 and 2009 with MMS using paraffin-embedded sections. RESULTS: Seventeen patients required one horizontal layer to clear their tumour, 10 patients needed two and eight patients needed three layers or more. The median preoperative clinical size was 6 cm(2) (range 0·75-54·8) and the median postoperative wound size was 46·8 cm(2) (range 4-145·2). Tumour persistence has not been observed in any of our patients after a median follow-up duration of 29·5 months (range 6-146). CONCLUSIONS: We present 35 DFSP patients, none of whom showed persistent tumour after treatment with 'slow' MMS using paraffin sections. We advocate MMS as the treatment of choice for DFSP, especially for tumours over the head and neck region where tissue conservation is particularly important.

A randomized double-blind controlled trial to compare a triclosan-containing emollient with vehicle for the treatment of atopic dermatitis.

The use of topical antiseptics in the treatment of atopic dermatitis (AD) has previously been explored. However, no triclosan-containing leave-on emollient has been evaluated previously, to our knowledge. The aims of this study were to assess the safety and efficacy of an emollient containing triclosan compared with the emollient alone (vehicle) for the treatment of AD. Eligible patients with mild to moderate AD were randomized to receive either the study cream or vehicle. All patients also received a low-potency corticosteroid cream to use during the treatment phase of the study if necessary. Patients were assessed for severity according to the SCORing Atopic Dermatitis (SCORAD) Index, amount of corticosteroid used, patient assessment of cream, and adverse events (AEs). In total, 60 patients received either the study cream or vehicle, and an intention-to-treat analysis was performed. At day 14, there was a significant decrease in SCORAD from baseline for the study cream compared with vehicle (P < 0.05). At day 27, although there was an improved mean reduction from baseline, this was no longer significant (P > 0.05). Only four patients had mild treatment-related AEs. The mean total amount of topical steroid applied by the patients using the study was significantly lower than that used by controls (P = 0.40). Triclosan-containing leave-on emollient was safe and highly acceptable to patients. However, the overall benefit on day 27 was not significant. Nevertheless, the amount of topical steroid used by patients was significantly less with the study cream than with the vehicle, thus further studies are needed to confirm its steroid-sparing effect.

[A family of tumor necrosis factor receptor-associated periodic syndrome].

Objective: To analyze the clinical manifestations and gene variations of tumor necrosis factor receptor-associated periodic syndrome (TRAPS). Methods: Clinical data and gene testing of four children and three adult relatives in a family from Puning, Guangdong were retrospectively analyzed. CD4(+)T cells, CD8(+)T cells, B cells, monocytes and NK cells were assessed by flow cytometry. Plasma level of TNFR receptors were assessed by enzyme linked immunosorbent assay (ELISA). TNFRSF1A gene variation was identified by second generation sequencing. Swiss-Model was used to analyze the potential impact of TNFRSF1A gene variation on its protein tertiary structure. Results: For all the patients,periodic fever was the main clinical feature,combined with arthralgia,myalgia,multiple serositis,periorbital edema and migratory cutaneous rash,accompanied with elevated level of acute-phase reactants and increased white blood cell counts during each episode. This disease was found in both gender and every generation in this family. The median age of onset was 2 years, ranging from 6 months to 30 years. The plasma level of TNFR1 of the patients range from 0 to 12.4 ng/L,which was lower than that of the normal controls range from 18.0~22.2 ng/L,while the level of TNFR2 was normal. Also, the numbers of T cells, B cells and monocytes were within normal range; however,number of NK cells in the patients (0.070±0.034) was lower than that in the normal controls (0.152±0.122). The TNFRSF1A variation,located in exon 3: c.295T>A (p.C99S),was found in the proband as well as the other 6 family members,which could induce change of the side chain of amino acid according to the prediction of the three-dimensional structure,subsequently affecting the binding to the receptor. Conclusions: TRAPS is characterized by periodic fever,arthralgia,myalgia,multiple serositis,periorbital edema and migratory cutaneous rash,with a significant decrease in plasma level of TNFR1 and NK cells. The gene sequencing analysis revealed a pathogenic variation in TNFRSF1A gene.

Clinical predictors of acute respiratory acidosis during exacerbation of asthma and chronic obstructive pulmonary disease.

Mechanical ventilation (MV) during exacerbation of asthma or chronic obstructive pulmonary disease (COPD) is unequivocally needed when apnoea, cardiorespiratory arrest, coma, hypoxia or treatment failure is present. The need is less clear when the patient can respond, has intact airway reflexes and spontaneous respiration. In this situation, acidosis is an important factor in the decision to institute MV. This study aimed to provide a clinical means of identifying patients with acute respiratory acidosis (ARA) in a setting where blood gas analysis is unavailable. We undertook a prospective, observational study of consecutive patients who presented to two emergency departments with severe and life-threatening exacerbation of asthma or COPD. Each underwent clinical assessment, treatment and blood gas analysis. The outcome measure was ARA or mixed ARA and metabolic acidosis. A total of 127 episodes in patients aged 15-90 years (65.3% males and 34.7% females) were included in the study. Of these, 62.2% had asthma and 37.8% had COPD; 71.7% had life-threatening and 28.3% had severe attacks. Overall, the adjusted odds ratio (and 95% confidence intervals) for predictors of ARA were 7.09 (1.79-28.06) for drowsiness, 4.11 (1.31-12.88) for flushing, 3.34 (1.01-11.02) for having COPD and 2.86 (1.01-8.07) for intercostal retractions. In conclusion, with drowsiness, the likelihood of ARA is about seven times higher. The presence of flushing, COPD and intercostal retractions also increase the risk of ARA.

Case reports on acute toluene poisoning during parquet flooring.

We report two cases of acute toluene poisoning occurring during parquet flooring. Inhalation is the major route of absorption in the workplace, owing to the high volatility of the compound. Such patients should be monitored closely for respiratory distress, central nervous system (CNS) depression and cardiac arrhythmias. Both our patients manifested signs of CNS depression and one had bronchospasm aborted by salbutamol Industries using toluene must ensure that precautions like adequate ventilation are taken to protect their workers.

The acute presentation of pulmonary thromboembolism: a retrospective viewpoint.

INTRODUCTION: Acute pulmonary thromboembolism (PE) has been considered rare among Asians. We aim to describe the frequency and clinical features of this condition in a hospital in Singapore. Among patients admitted by the Emergency Department (ED), comparisons were made between those primarily diagnosed in the ED and those who were not. MATERIALS AND METHODS: Retrospective review of all cases of radiologically proven acute PE over a 20-month period. RESULTS: Sixty-two patients were identified. The mean age was 61.5 +/- 18.0 years with a female to male ratio of 1.8:1. There were more Malays compared to other races. There were also more Caucasians, given the proximity of the hospital to the airport and the inclusion of tourists. The commonest symptoms were dyspnoea and chest pain, while the commonest signs were tachycardia and tachypnoea. Prolonged immobilisation was the commonest risk factor. Electrocardiographic S1Q3T3 pattern was seen in more patients compared to Western studies. Cardiomegaly was the commonest chest X-ray finding. Thirty-two patients were identified to have a source of embolisation. Overall mortality rate was 21%. The ED diagnosed 36% of the cases. Alternative admitting diagnoses were predominantly ischaemic heart disease and pneumonia. The group diagnosed in the ED were notably female (P = 0.044), Caucasian (P = 0.002) and had prolonged immobilisation (P = 0.025) prior to the onset of PE. CONCLUSION: Acute PE is not as rare here as previously thought. Clinical features reveal more similarities than differences compared to other studies in the literature. We advocate a high index of suspicion for earlier diagnosis in the ED.

[Determination of flecainide concentration in blood plasma by HPLC and pharmacokinetic parameters in volunteers].

A high performance liquid chromatographic method (ultraviolet detection) for the determination of flecainide concentration in human plasma was reported. Flurazepam (dalmadorm) was used as the internal standard. A mixture of methanol and deionized water containing ion paired reagent served as the mobile phase. The regression equation of flecainide was: y = 0.0017x + 0.0131, r = 0.9975. The extraction recoveries exceeded 94%, and the coefficients of variation (both within the same day and in different days) were less than 5%. The pharmacokinetic parameters in Chinese volunteers after taking flecainide were: Ka = 0.908h-1, T1/2 = 8.131h, peats time = 3.487h, AUC = 441.8ng.h/ml. The mean plasma concentration of flecainide in cases responded well to this drug was 423.6 +/- 227.4ng/ml.

Scrotal pyoderma gangrenosum associated with Crohn's disease.

Scrotal pyoderma gangrenosum is uncommon. We present a 17-year-old Chinese male patient with newly diagnosed Crohn's disease presenting with scrotal pyoderma gangrenosum. Biopsy and other investigations were done to diagnose and look for associated diseases of pyoderma gangrenosum. Treatment with high-dose prednisolone failed. Subsequent treatment with oral cyclosporine was successful.