A macrophage-specific synthetic promoter for therapeutic application of adiponectin.

Foam cell formation from macrophage is a major cause of atherosclerosis. An efficient macrophage-specific promoter is required for the targeting to macrophages. In this study, we develop a macrophage-specific synthetic promoter for the therapeutic application of adiponectin (APN), an antiatherogenic gene. Synthetic promoter-146 (SP146), registered on the NCBI website (http://www.ncbi.nlm.nih.gov/nuccore/DQ107383), was tested for promoter activities in two non-macrophage cell lines (293 T, HeLa) and a macrophage cell line (RAW264.7, bone marrow-derived macrophages). To enforce macrophage specificity, partial elements of p47(phox) including the PU.1 site with various lengths (-C1, -C2 and -C3) were inserted next to the synthetic promoters. SP146-C1 showed the highest specificity and efficacy in RAW264.7 cells and was selected for development of an APN-carrying macrophage-specific promoter. Green fluorescent protein (GFP)- or APN-expressing lentivirus under SP146-C1 (Lenti-SP-GFP or Lenti-SP-APN, respectively) showed the highest expression efficacy in RAW264.7 cells compared with the non-macrophage cell lines. APN overexpression in RAW264.7 cells successfully inhibited intracellular lipid accumulation, and atherosclerotic lesions and lipid accumulation were significantly reduced by Lenti-SP-APN in ApoE-/- atherosclerosis mice. In conclusion, the synthetic promoter SP146-C1, combined with a p47(phox) promoter element, was successfully developed to target macrophage, and macrophage-specific introduction of APN under SP146-C1 was shown to ameliorate the atherosclerotic pathology.

Genetic analysis of duck circovirus in Pekin ducks from South Korea.

The genetic organization of the 24 duck circovirus (DuCV) strains detected in commercial Pekin ducks from South Korea between 2011 and 2012 is described in this study. Multiple sequence alignment and phylogenetic analyses were performed on the 24 viral genome sequences as well as on 45 genome sequences available from the GenBank database. Phylogenetic analyses based on the genomic and open reading frame 2/cap sequences demonstrated that all DuCV strains belonged to genotype 1 and were designated in a subcluster under genotype 1. Analysis of the capsid protein amino acid sequences of the 24 Korean DuCV strains showed 10 substitutions compared with that of other genotype 1 strains. Our analysis showed that genotype 1 is predominant and circulating in South Korea. These present results serve as incentive to add more data to the DuCV database and provide insight to conduct further intensive study on the geographic relationships among these virus strains.

Clinical standards for the management of adverse effects during treatment for TB.

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

Clinical standards for the dosing and management of TB drugs.

BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.

Analysis of efficacy and safety of core-needle biopsy versus fine-needle aspiration cytology in patients with cervical lymphadenopathy and salivary gland tumour.

In this study, we compared the diagnostic accuracy and safety of fine-needle aspiration cytology and core-needle biopsy in patients with cervical lymphadenopathy or salivary gland tumour, and provided a basis for selecting the appropriate diagnostic method in clinical situations. A total of 278 patients were included in this study. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 66.7% and 100%, respectively, and negative predictive values were 92.6% and 100%, respectively, for diagnosing malignancy. In diagnosing lymphoma, fine-needle aspiration cytology gave false-negative results in all patients. In diagnosing tuberculous lymphadenopathy, the sensitivities of fine-needle aspiration cytology and core-needle biopsy were 33.3% and 91.15%, respectively, and the negative predictive values were 90.0% and 95.1%, respectively. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 42.9% and 100% in diagnosing malignant salivary gland tumours, and the negative predictive values were 91% and 100%, respectively. The results of this study showed that core-needle biopsy was superior in diagnosing and distinguishing critical diseases such as malignant lymphadenopathy and tuberculosis in patients with cervical lymphadenopathy and salivary gland tumour.

Efficacy of ultrasound-guided core needle gun biopsy in diagnosing cervical lymphadenopathy.

OBJECTIVE: Ultrasound-guided fine needle aspiration cytology (US-FNA) is useful for diagnosing cervical lymphadenopathy. However, FNA, has a high false negative rate, especially in patients with lymphoma. Ultrasound-guided core needle gun biopsy (US-CNB) has recently become important for diagnosing cancers, but its value remains undetermined. This study evaluates the efficacy of US-CNB, performed in an outpatient setting, in diagnosing cervical lymphadenopathy and the spectrum of related diseases. MATERIALS AND METHODS: This retrospective study included 79 subjects who were not squamous cell carcinoma suspects and did not have a history of malignancy between January 2006 and July 2009. A US-CNB was performed on enlarged cervical lymph nodes (>1.0cm) in all subjects. Diagnostic sensitivity, specificity, and accuracy of US-CNB in differentiating between malignant and benign lymphadenopathy were evaluated. All enrolled subjects underwent a planned US-FNA before the study US-CNB was performed. Results of US-CNB and US-FNA were compared. RESULTS: The correct histopathological diagnoses were made in 73 of 79 subjects (91.1%) using US-CNB samples. Of these, the most common diagnoses were reactive hyperplasia (26 subjects), Kikuchi's disease (17 subjects), tuberculous lymphadenitis (15 subjects), lymphoma (8 subjects), and metastatic carcinoma (3 subjects). The US-CNB was very good at differentiating between malignant and benign lymphadenopathy, with a diagnostic sensitivity, specificity, and accuracy of 91.6%, 100%, and 98.6%, respectively. Additionally, US-CNB was more accurate than US-FNA in identifying lymphoma (88.8% vs. 11.1%) and Kikuchi's disease (89.4% vs. 29.4%). No US-CNB related-complications were observed. CONCLUSION: The US-CNB is safe, effective, and has a high diagnostic yield for cervical lymphadenopathy. The US-CNB may also be useful for diagnosing lymphoma and Kikuchi's disease.

Prognostic significance of tumour progression and human papillomavirus in advanced tonsillar cancer classified as stage IVa.

OBJECTIVE: To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas. METHODS: Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53. RESULTS: Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours. CONCLUSION: The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.

Verapamil responsive incessant ventricular tachycardia resulting in severe ventricular dysfunction in a young child: successful management with oral verapamil.

In young children with incessant ventricular tachycardia and severe ventricular dysfunction, the management of tachycardia with conventional antiarrhythmic drugs remains a major therapeutic challenge because most of these drugs can further depress myocardial function. We report a four year old boy with verapamil responsive incessant ventricular tachycardia and severe ventricular dysfunction in whom oral verapamil treatment eliminated both the arrhythmia and the picture of dilated cardiomyopathy. On oral verapamil, the patient remains asymptomatic without recurrence of the ventricular tachycardia over a follow up period of 10 months.

The reliability and acceptability of telemedicine for patients with schizophrenia in Korea.

We conducted a pilot study to evaluate telemedicine for patients with schizophrenia. The telemedicine system was connected over the ordinary telephone network at 33 kbit/s. A computer-based patient record was used to view patient summaries and to allow nursing notes to be entered at the patient's home. Fifteen patients with schizophrenia were assessed over the telemedicine system and 15 patients were assessed face to face, using the Brief Psychiatric Rating Scale (BPRS). Our low-bandwidth telemedicine system appeared to be as reliable as higher-bandwidth ISDN systems. In addition, the patients' acceptance of the telemedicine interview, in terms of comfort, ease of self-expression, quality of interpersonal relationship and usefulness, was good in most cases. The only factors significantly affecting the patients' level of acceptance of their particular type of interview were the assessment type (i.e. whether the patient had had a telemedicine assessment or not) and their BPRS score. Since the system was of low cost and was easy to interface with a notebook computer, it could be used support other home-health nursing services.

Response characteristics for thermal and pressure devices commonly used for monitoring nasal and oral airflow during sleep studies.

We examined thermocouple and pressure cannulae responses to oral and nasal airflow using a polyester model of a human face, with patent nasal and oral orifices instrumented with a dual thermocouple (F-ONT2A, Grass) or a dual cannula (0588, Braebon) pressure transducer (± 10 cm H2O, Celesco) system. Tidal airflow was generated using a dual compartment facemask with pneumotachographs (Fleisch 2) connected to the model orifices. During nasal breathing: thermocouple amplitude = 0.38 Ln [pneumotachograph amplitude] + 1.31 and pressure cannula amplitude = 0.93 [pneumotachograph amplitude](2.15); during oral breathing: thermocouple amplitude = 0.44 Ln [pneumotachograph amplitude] + 1.07 and pressure cannula amplitude = 0.33 [pneumotachograph amplitude](1.72); (all range ∼ 0.1-∼ 4.0 L s(-1); r(2) > 0.7). For pneumotachograph amplitudes <1 L s(-1) (linear model) change in thermocouple amplitude/unit change in pneumotachograph amplitude was similar for nasal and oral airflow, whereas nasal pressure cannula amplitude/unit change in pneumotachograph amplitude was almost four times that for oral. Increasing oral orifice area from 0.33 cm(2) to 2.15 cm(2) increased oral thermocouple amplitude/unit change in pneumotachograph amplitude by ∼ 58% but decreased pressure cannula amplitude/unit change in pneumotachograph amplitude by 49%. For pneumotachograph amplitudes up to 1 L s(-1), alterations in inspiratory/expiratory ratios or total respiratory time did not affect the sensitivity of either nasal or oral pressure cannulae or the nasal thermocouple, but the oral thermocouple sensitivity was influenced by respiratory cycle time. Different nasal and oral responses influence the ability of these systems to quantitatively assess nasal and oral airflow and oro-nasal airflow partitioning.

Effect of voice therapy after phonomicrosurgery for vocal polyps: a prospective, historically controlled, clinical study.

OBJECTIVE: This study aimed to evaluate the efficacy of post-operative voice therapy after phonomicrosurgery for vocal polyp removal. METHODS: The study retrospectively enrolled 55 consecutive patients who had undergone voice therapy after phonomicrosurgery for vocal polyp removal occurring between June 2010 and June 2011. A historical group of 63 similar patients not receiving voice therapy was used as an external control. We compared voice analysis parameters and Voice Handicap Index scores for the two groups. RESULTS: Most objective and subjective voice outcome parameters were significantly improved after surgical treatment. Although the study and control groups showed no significant difference regarding objective parameters (using acoustic and aerodynamic analysis) or the subjective parameters assessed using the grade-roughness-breathiness-asthenia-strain scale, the study group had significantly better final Voice Handicap Index scores. CONCLUSION: Following surgery for vocal polyps, post-operative voice therapy can improve patients' vocal discomfort, emotional responses and everyday self-perception.

Systemic sclerosis sine scleroderma associated with Wolff-Parkinson-White syndrome.

The term "systemic sclerosis sine scleroderma" (ssSSc) has been used to designate a rare progressive systemic sclerosis of visceral organs without skin manifestations. A variety of visceral organs, including the gastrointestinal tract, lung, heart, and kidney, can be involved. We describe a case of 59-year-old female patient with both Wolff-Parkinson-White (WPW) syndrome and ssSSc. She was diagnosed as having ssSSc with Raynaud's phenomenon, anti-nuclear antibody (ANA) and anti-topoisomerase antibody positivity, interstitial pulmonary infiltrates, suspected pulmonary hypertension, subclinical oesophageal dysmotility but no skin thickening. She had a history of paroxysmal tachycardia together with Raynaud's phenomenon and exercise-induced dyspnoea. Electrophysiological study confirmed WPW syndrome with left posterior bypass tract. This case highlights cardiac arrhythmia caused by WPW syndrome as a clinical manifestation of the heart in ssSSc.

Effects of incremental doses of procainamide in patients with sustained uniform ventricular tachycardia.

INTRODUCTION: Although intravenously administered procainamide has been used extensively during electropharmacologic testing for more than 10 years, there is little information available on the effects of incremental dosing of procainamide in patients with inducible, monomorphic ventricular tachycardia (VT). METHODS AND RESULTS: Twenty-nine patients with coronary artery disease had sustained monomorphic VT reproducibly induced in the baseline, drug-free state. Programmed stimulation was repeated 5 minutes after loading infusion (50 mg/min) of 7.5 and 15 mg/kg (all patients) and 22.5 mg/kg of procainamide (15 patients), while maintaining continuous infusion of 0.055, 0.11, and 0.165 mg/kg per minute after each increment in dose, respectively. Corresponding procainamide plasma concentrations were 5.6 +/- 2, 10.5 +/- 3, and 14.5 +/- 3 mg/L before, and 4.7 +/- 2, 9.6 +/- 3, and 14.6 +/- 4 mg/L after electrophysiologic study at each increment in dose of procainamide, respectively. Each incremental dose of procainamide resulted in significant prolongation of tachycardia cycle length and QRS duration during sinus rhythm and right ventricular pacing. Five (17%), 7 (24%), and 1 (7%) patients, respectively, had no inducible sustained VT following the incremental dosing of procainamide. Three of five patients who had no inducible VT at 7.5 mg/kg had VT induced again at a higher dose of procainamide. Four of 24 patients whose VT remained inducible at 7.5 mg/kg of procainamide had no VT induced at 15 mg/kg of procainamide. Twelve (41%), 15 (52%), and 6 (40%) patients, respectively, no longer had VT with baseline morphology induced following the incremental dosing of procainamide. VT with new morphology compared to baseline was induced in more than 40% of patients at one or more of the three different procainamide dosing regimens. The mean cycle length of VTs with new morphology was significantly shorter than the cycle length of tachycardias with baseline morphology at each particular dose of procainamide. CONCLUSION: Similar serum procainamide concentrations before and after programmed stimulation can be achieved at the described dosing regimen. Although 7.5 and 15 mg/kg of procainamide are both effective in suppressing induction of all VT in 20% to 25% of patients, non-inducibility at a particular dose of procainamide does not predict noninducibility at a respectively higher or lower dose. New morphologies of VT that are frequently faster than VTs with baseline morphology at a particular dose of procainamide can be induced in approximately half of the patients, and the clinical significance of these arrhythmias remains to be determined.

Suprasternal M-mode echocardiography of the right pulmonary artery as a model for investigation of pulmonary hemodynamics in essential hypertension.

The right pulmonary artery (RPA) dimensions of 85 asymptomatic mild or moderate hypertension (HT) patients, divided into 6 subgroups according to the left ventricular (LV) mass index (125g/m2 BSA) left atrial (LA) dimension index (2.2cm/m2 BSA), and 40 normal subjects were studied utilizing suprasternal M-mode echocardiography in order to examine the consistency of the elevated PA pressure in essential HT and to understand its pathogenesis. The RPA dimension at late diastole, at the end of the right ventricular isovolumic contraction, and at systole in the subgroup of HT without LV hypertrophy and LA enlargement was significantly increased compared with those of the normal group (18.4 +/- 2.8 vs 16.2 +/- 2.3mm, 19.6 +/- 3.0 vs 17.2 +/- 1.3mm, 22.5 +/- 2.5 vs 20.8 +/- 1.9mm, p less than 0.05, respectively) and varied in close correlation with systolic and diastolic BP and the dimension of the aorta. The dimensions in the other 5 subgroups were the same and were not further affected by the LV mass and LA dimension. The above results suggest that elevated systemic BP per se is associated with the dilation of the RPA supposedly caused by increased PA resistance, besides the backward effect of the increased LV and/or LA pressure which may affect the increase of PA pressure.

Early outcome of PTCA in totally occluded coronary arteries.

BACKGROUND: Since percutaneous transluminal coronary angioplasty (PTCA) was first introduced in 1977 by Gruentzig as a treatment for proximal short-segmental, non-calcified, concentric isolated coronary stenosis, it has been used with increasing frequency in patients of symptomatic coronary artery disease with broader indications, including patients with multi-vessel disease, unstable angina, acute myocardial infarction and totally occluded coronary arteries. Among these, total coronary occlusion constitutes a subdivision with specific features that require separate evaluation. The purpose of this study was to determine the initial results of PTCA for total coronary occlusion. METHODS: Thirty-five patients with manifested ischemic heart disease with totally occluded coronary arteries, documented by coronary angiography, underwent recanalization procedure by PTCA between Jan. 1990 and Oct. 1991. RESULTS: Thirty-five patients were comprised of 20 acute myocardial infarction (MI), 7 old MI and 8 unstable angina. Eighteen (50.1%) patients had one major atherosclerosis risk factor and 10 (29.4%) had two or more. PTCA for total coronary artery occlusion was attempted in the left anterior descending artery (LAD) in 16 patients, right coronary artery (RCA) in 11, left circumflex artery (LCx) in 2 and protected left main in one. PTCA was successful in 23 patients (66%): LAD in 11/18 (61%) and RCA 11/14 (79%), showing significantly higher success rate with RCA than LAD (p < 0.05). Primary success rate of PTCA in accordance with the duration of the total occlusion estimated on the basis of clinical and angiographic data was 71% (15/21) when less than two weeks, 63% (5/8) when between 2 to 12 weeks, and 50% (3/6) longer than 12 weeks. Mean duration of the total occlusion in successful PTCA was 1.4 months (range; 10 days-5 months) and, 1.7 months (range; 3 weeks-3 years) in failed PTCA. Diameter stenosis of the lesions was significantly decreased from 100% to 19.7% after successful PTCA. There was no death but 2 patients were complicated with coronary artery embolization occluding major distal branches. CONCLUSION: The study suggested that PTCA of total coronary artery occlusion can be performed safely and effectively in selected cases and might be more successful in the lesion with shorter duration of occlusion.

Head-up tilt test with isoproterenol provocation in syncope of unknown origin.

OBJECTIVES: Head-up tilt test (HUT) has been reported to be useful in the evaluation of syncope of unknown origin (SUO). However, the sensitivity of HUT with no pharmacologic provocation was relatively low and variable, ranging 32 approximately 70%. Therefore, several protocols of HUT with different degrees and durations of the tilt and modes of provocation were proposed. The purpose of this study was to determine the value of the multi-stage head-up tilt test with isoproterenol provocation (HUT-isp) in the evaluation of SUO and drug efficacy. METHODS: Sixty-seven patients presenting with SUO and 30 control subjects with no history of syncope underwent the HUT-isp. Blood pressure (BP) was measured every 2 min and whenever the patient complained of any symptom, and cardiac rhythm was continuously monitored. The HUT-isp consisted of 3 stages: first for 20 min with no provocation, second and third stages with infusion of isoproterenol for 10 min each at a rate of 2 micrograms/min and 5 micrograms/min, respectively. A positive HUT-isp was defined when syncope or presyncope was reproduced, accompanied by hypotension (< 80 mmHg) or bradycardia (< 40/min) or both, and positive responses were classified into vasodepressive, cardioinhibitory and mixed type. RESULTS: The HUT-isp was positive in 56 (83.6%) of 67 patients with SUO and 10 (33.3%) of 30 control subjects. The type of positive responses was vasodepressive in 41 (73.2%), cardioinhibitory in 4 (7.1%) and mixed in 11 (19.6%). The sensitivity of the HUT-isp in diagnosing vasovagal syncope was 83.6%, specificity 66.7% and positive predictive value 84.8%. Positive responses were developed most frequently in the 3rd stage: 76.8% in patients, 70% in controls. The effect of 3 drugs (carteolol, aminophylline and disopyramide) was evaluated in 27 patients with a repeat HUT-isp. Carteolol was effective in 12 (85.7%) of 14 patients, disopyramide in 7 (58. 3%) of 12 and aminophylline in 1 (14.3%) of 7. During the follow-up period of 175 +/- 212 days (26 approximately 623 days), none of the 20 patients with a negative repeat HUT-isp developed a recurrent syncope. CONCLUSION: The HUT-isp is thought safe and useful to evaluate syncope of unknown origin and to guide effective drug therapy.