Machine learning based deconvolution of microarray atrial samples from atrial fibrillation patients reveals increased fractions of follicular CD4+ T lymphocytes and gamma-delta T cells.

A potential relationship between T cell immunity and development of atrial fibrillation (AF) has been proposed. Historically in AF patients it has been reported that peripheral blood had elevated CD4+ T cells. However few studies have explored whether there is a direct increase of CD4+ T cells in atrial tissues with AF. In this study, public domain micro-array dataset of cardiac surgery patients with atrial tissue biopsies in AF and non-AF patients have been used to explore immune cell subsets. Machine learning based deconvolution of permanent atrial fibrillation microarray atrial samples was applied using Cibersort to enumerate the relative fractions of twenty-two different leukocyte sub-populations. Cibersort enumerated significantly increased fractions of follicular CD4+ T lymphocytes and gamma-delta T cells in the atria of permanent AF subjects. Gene expression analysis of permanent AF microarray tissue samples with elevated follicular CD4+ T cell fractions with gene pathways associated with myocardial substrate remodelling. That is both integrin and non-integrin mediated gene interactions between inflammatory cells and the extra cellular matrix, including infiltrating follicular CD4+ T cells that trafficked to the atria by virtue of the repertoire of cell surfaced expressed adhesion molecules. Additionally, IL-17 and other interleukin inflammatory gene heat maps were associated with enhanced CD4+ follicular T cell expression in our profiled atrial tissues with AF. These observations suggest that atrial structural remodelling was associated with the presence of pathogenic T cell mediated inflammation, present in AF atria but not in non-AF atria.

Endothelium-Independent Vasodilatory Effect of Sailuotong (SLT) on Rat Isolated Tail Artery.

BACKGROUND: Sailuotong (SLT) is a standardized three-herb formulation consisting of extracts of Panax ginseng, Ginkgo biloba, and Crocus sativus for the treatment of vascular dementia (VaD). Although SLT has been shown to increase cerebral blood flow, the direct effects of SLT on vascular reactivity have not been explored. This study aims to examine the vasodilatory effects of SLT and the underlying mechanisms in rat isolated tail artery. METHODS: Male (250-300 g) Wistar Kyoto (WKY) rat tail artery was isolated for isometric tension measurement. The effects of SLT on the influx of calcium through the cell membrane calcium channels were determined in Ca2+-free solution experiments. RESULTS: SLT (0.1-5,000 µg/ml) caused a concentration-dependent relaxation in rat isolated tail artery precontracted by phenylephrine. In the contraction experiments, SLT (500, 1,000, and 5,000 µg/mL) significantly inhibited phenylephrine (0.001 to 10 µM)- and KCl (10-80 mM)-induced contraction, in a concentration-dependent manner. In Ca2+-free solution, SLT (500, 1,000, and 5,000 µg/mL) markedly suppressed Ca2+-induced (0.001-3 mM) vasoconstriction in a concentration-dependent manner in both phenylephrine (10 µM) or KCl (80 mM) stimulated tail arteries. L-type calcium channel blocker nifedipine (10 µM) inhibited PE-induced contraction. Furthermore, SLT significantly reduced phenylephrine-induced transient vasoconstriction in the rat isolated tail artery. CONCLUSION: SLT induces relaxation of rat isolated tail artery through endothelium-independent mechanisms. The SLT-induced vasodilatation appeared to be jointly meditated by blockages of extracellular Ca2+ influx via receptor-gated and voltage-gated Ca2+ channels and inhibition of the release of Ca2+ from the sarcoplasmic reticulum.

Detection of Anomalous Cervical Internal Carotid Artery Branches by Colour Duplex Ultrasound.

OBJECTIVES: Conventional anatomical descriptions of the cervical internal carotid artery (ICA) report that no branches arise from this segment. However reports of ICA branches exist. The study aim was to determine the prevalence of anomalous branches of the ICA using colour duplex ultrasound (CDU). METHODS: Four hundred consecutive patients (800 carotid vessels) referred to a tertiary hospital vascular laboratory for investigation of carotid disease were included. A clear differentiation of a low resistive ICA and a high resistive external carotid artery (ECA) waveform was required. CDU was performed on a Philips IU22 ultrasound system with a 9-3 MHz linear array transducer employing a standard carotid imaging protocol. The origin of each ICA branch was identified using B-mode and CDU. Anatomical orientation of ICA branches and distance from bifurcation was recorded and spectral CDU analysis was performed. RESULTS: Twenty ICA branches, tracking cephaladly, were detected in 16 patients (4%), or 2.5% (20/800) vessels. The median age was 73 years; 50% were female and 50% male. All patients demonstrated a single branch [unilateral anomaly (n = 12 patients), bilateral anomaly (n = 4) patients]. Eighty-five percent arose from the posterior wall of the ICA. The median distance from ICA bifurcation was 4 mm (range 0-18 mm). ICA branch diameters ranged from 1.2 mm to 2.4 mm (median 1.4 mm, mean 1.6 mm). Eighty percent of ICA branches had less than 50% stenosis. Spectral analysis revealed high resistive waveforms in all branches. CONCLUSIONS: Branches from the ICA exist and can be characterised with CDU. Prevalence in a tertiary hospital referral cohort is 4%. Given their potential clinical implications, standard carotid imaging protocols should consider routine assessment and reporting of ICA branches.

The ethnicity-specific association of biomarkers with the angiographic severity of coronary artery disease.

BACKGROUND: Risk factor burden and clinical characteristics of patients with coronary artery disease (CAD) differ among ethnic groups. We related biomarkers to CAD severity in Caucasians, Chinese, Indians and Malays. METHODS: In the Dutch-Singaporean UNICORN coronary angiography cohort (n = 2033) we compared levels of five cardiovascular biomarkers: N-terminal pro-brain natriuretic peptide (NTproBNP), high-sensitivity C-reactive protein (hsCRP), cystatin C (CysC), myeloperoxidase (MPO) and high-sensitivity troponin I (hsTnI). We assessed ethnicity-specific associations of biomarkers with CAD severity, quantified by the SYNTAX score. RESULTS: Adjusted for baseline differences, NTproBNP levels were significantly higher in Malays than in Chinese and Caucasians (72.1 vs. 34.4 and 41.1 pmol/l, p < 0.001 and p = 0.005, respectively). MPO levels were higher in Caucasians than in Indians (32.8 vs. 27.2 ng/ml, p = 0.026), hsTnI levels were higher in Malays than in Caucasians and Indians (33.3 vs. 16.4 and 17.8 ng/l, p < 0.001 and p = 0.029) and hsTnI levels were higher in Chinese than in Caucasians (23.3 vs. 16.4, p = 0.031). We found modifying effects of ethnicity on the association of biomarkers with SYNTAX score. NTproBNP associated more strongly with the SYNTAX score in Malays than Caucasians (ß 0.132 vs. ß 0.020 per 100 pmol/l increase in NTproBNP, p = 0.032). For MPO levels the association was stronger in Malays than Caucasians (ß 1.146 vs. ß 0.016 per 10 ng/ml increase, p = 0.017). Differing biomarker cut-off levels were found for the ethnic groups. CONCLUSION: When corrected for possible confounders we observe ethnicity-specific differences in biomarker levels. Moreover, biomarkers associated differently with CAD severity, suggesting that ethnicity-specific cut-off values should be considered.

Diabetes Mellitus, Cognitive Impairment, and Traditional Chinese Medicine.

Diabetes mellitus (DM) is a metabolic disorder affecting a large number of people worldwide. Numerous studies have demonstrated that DM can cause damage to multiple systems, leading to complications such as heart disease, cancer, and cerebrovascular disorders. Numerous epidemiological studies have shown that DM is closely associated with dementia and cognition dysfunction, with recent research focusing on the role of DM-mediated cerebrovascular damage in dementia. Despite the therapeutic benefits of antidiabetic agents for the treatment of DM-mediated cognitive dysfunction, most of these pharmaceutical agents are associated with various undesirable side-effects and their long-term benefits are therefore in doubt. Early evidence exists to support the use of traditional Chinese medicine (TCM) interventions, which tend to have minimal toxicity and side-effects. More importantly, these TCM interventions appear to offer significant effects in reducing DM-related complications beyond blood glucose control. However, more research is needed to further validate these claims and to explore their relevant mechanisms of action. The aims of this paper are (1) to provide an updated overview on the association between DM and cognitive dysfunction and (2) to review the scientific evidence underpinning the use of TCM interventions for the treatment and prevention of DM-induced cognitive dysfunction and dementia.

Detox diets for toxin elimination and weight management: a critical review of the evidence.

Detox diets are popular dieting strategies that claim to facilitate toxin elimination and weight loss, thereby promoting health and well-being. The present review examines whether detox diets are necessary, what they involve, whether they are effective and whether they present any dangers. Although the detox industry is booming, there is very little clinical evidence to support the use of these diets. A handful of clinical studies have shown that commercial detox diets enhance liver detoxification and eliminate persistent organic pollutants from the body, although these studies are hampered by flawed methodologies and small sample sizes. There is preliminary evidence to suggest that certain foods such as coriander, nori and olestra have detoxification properties, although the majority of these studies have been performed in animals. To the best of our knowledge, no randomised controlled trials have been conducted to assess the effectiveness of commercial detox diets in humans. This is an area that deserves attention so that consumers can be informed of the potential benefits and risks of detox programmes.

The impact of frontline risk-adapted strategy on the overall survival of patients with newly diagnosed multiple myeloma: an analysis of the Singapore multiple myeloma study group.

INTRODUCTION: Risk stratification is vital for prognostication and informing treatment decisions in multiple myeloma (MM). We study the prognostic values of the International Staging System (ISS) and underlying cytogenetics in the bortezomib era and assess the impacts of an upfront risk-adapted approach in the treatment of MM. METHODS: We compare the overall survival (OS) of 221 patients with MM diagnosed from 2006 to 2009 (era 2) where upfront bortezomib combination was approved for high-risk MM with the OS of 262 patients diagnosed from 2000 to 2005 (era 1) where bortezomib could only be administered at relapse. High-risk MM is defined by the presence of ISS III disease with renal impairment or adverse cytogenetics. RESULTS: Baseline characteristics were comparable between the 2 eras. At median follow-up of 20 months, 0% and 26% of patients had received frontline bortezomib in eras 1 and 2, respectively. The median OS were 4.2 yrs and not reached for eras 1 and 2, respectively (P = 0.03). On multivariate analysis stratified by era, the most significant prognostic factor shifts from cytogenetics in era 1 to the quality of response in era 2. CONCLUSION: Frontline use of bortezomib in a risk-adapted manner may avert early mortality and is better able to overcome adverse risks compared to its sequential use.

Multiple inflammatory and serum amyloid A positive telangiectatic hepatic adenomas with glycogenated nuclei arising in a background of nonalcoholic steatohepatitis.

The authors describe multiple telangiectatic or inflammatory adenomas in a 53-year-old woman with steatohepatitis who presented with acute right upper quadrant abdominal pain. Magnetic resonance imaging revealed 6 lesions consistent with multiple hepatic adenomas, 2 of which showed hemorrhage. She underwent right lobectomy and nonanatomical segment 2 liver resections and seven nodules ranging in size from 1.0 to 5.0 cm were identified. All nodules contained portal-like structures and ductular reaction, features seen in focal nodular hyperplasia, as well as significant inflammation, telangiectatic sinusoids and immunoreactivity for serum amyloid A, placing them according to a recently described classification systems as telangiectatic or inflammatory adenomas. The diffuse positivity of the serum amyloid A staining results in this case suggests an important diagnostic role of this stain in smaller tissue samples, such as in core biopsy specimens.

Primary isolation and detection of Helicobacter pylori from dyspeptic patients: a simple, rapid method.

The study aimed to develop a rapid and simple method for the primary isolation and detection of Helicobacter pylori from dyspeptic patients. Mucosal antral biopsy specimens were obtained from 136 consecutive dyspeptic patients diagnosed with peptic ulcer by endoscopy at Basra General Hospital, Iraq. From histopathological examination of biopsies, H. pylori was detected in 81 (59.6%) peptic ulcer patients. For bacterial culture, specimens were cultured in parallel on 2 media: the non-selective classic Columbia agar and the selective modified Columbia urea agar (MCUA). MCUA showed a higher isolation rate than classic Columbia agar (67.6% versus 44.1% of patients), and the results were obtained faster (24 hours versus 5-7 days) with more clear-cut identification.

Primary isolation and detection of Helicobacter pylori from dyspeptic patients: a simple, rapid method

The study aimed to develop a rapid and simple method for the primary isolation and detection of Helicobacter pylori from dyspeptic patients. Mucosal antral biopsy specimens were obtained from 136 consecutive dyspeptic patients diagnosed with peptic ulcer by endoscopy at Basra General Hospital, Iraq. From histopathological examination of biopsies, H. pylori was detected in 81 [59.6%] peptic ulcer patients. For bacterial culture, specimens were cultured in parallel on 2 media: the nonselective classic Columbia agar and the selective modified Columbia urea agar [MCUA]. MCUA showed a higher isolation rate than classic Columbia agar [67.6% versus 44.1% of patients], and the results were obtained faster [24 hours versus 5-7 days] with more clear-cut identification

Direct comparison of 18F-fluorodeoxyglucose coincidence gamma camera tomography with gallium scanning for the staging of lymphoma.

BACKGROUND: The present study compared the performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) using a coincidence dual-head gamma camera (FDG Co-PET) with 67gallium scinti graphy (GS) in pretreatment staging of lymphoma. METHODS: A total of 46 patients underwent FDG Co-PET, computed tomography (CT) scanning and GS for pretreatment staging of lymphoma (40 newly diagnosed and recurrence) between November 1997 and December 1999. RESULTS: Histological subgroups comprised low grade (8 patients), intermediate grade (25) high-grade (3) non-Hodgkin's lymphoma and Hodgkin's disease (10). Based on clinical assessment, CT scan findings and biopsy, 100 nodal sites and 15 extra-nodal sites were deemed positive. FDG Co-PET was superior to GS in nodal site positivity rate (97%vs 79%, P < 0.0001). Compared with GS, FDG Co-PET detected 39 more abnormal sites in 22 patients (48%), of which 28 sites were validated by biopsy, CT and/or progress FDG Co-PET scanning. There was only one proven false negative FDG site in the spleen. CT + FDG Co-PET led to upstaging in 2 patients (4%), compared to CT + GS. CONCLUSION: FDG Co-PET shows potential for providing an accurate means for pretreatment staging of lymphoma and can detect extra sites of disease activity compared to GS.

Multilocus linkage analysis of the German asthma data.

We analyzed data from the German Asthma Genetics Group with three methods that utilize pedigree-specific nonparametric linkage scores to facilitate the search for multiple independent and interacting susceptibility loci. The three methods included a conditional analysis, logistic regression, and neural networks. Although there were differences, the three methods identified many of the same susceptibility loci. The most consistent evidence was provided for loci on chromosomes 1, 2, 6, 9, and 15. Both the conditional and the logistic regression analyses suggested an epistatic relationship between loci on chromosomes 2 and 9. The logistic regression analysis further revealed evidence for locus heterogeneity between loci on chromosomes 6 and 15. Finally, the neural network analysis identified a potential locus on chromosome 17 that was not identified in the other analyses.

Fluorine-18 FDG dual-head gamma camera coincidence imaging of radiation pneumonitis.

A 69-year-old man with inoperable stage I squamous cell carcinoma of the lung underwent a radical course of radiotherapy combined with platinum-based chemotherapy. Fluorine-18 fluorodeoxyglucose (FDG) imaging with a dual-head coincidence gamma camera system (Co-PET) diagnosed radiation pneumonitis 1 month after completion of radiotherapy, when the clinical and radiographic signs were atypical and more suggestive of carcinomatous lymphangitis. Treatment with oral steroids was begun based on FDG scan findings, with prompt clinical benefit as would be expected for radiation pneumonitis.

Multicenter clinical trial to evaluate the efficacy of correction for photon attenuation and scatter in SPECT myocardial perfusion imaging.

BACKGROUND: Soft tissue attenuation is a prominent cause of single-photon emission computed tomography (SPECT) imaging artifacts, which may result in reduced diagnostic accuracy of myocardial perfusion imaging. A method incorporating simultaneously acquired transmission data permits nonuniform attenuation correction and when incorporating scatter correction and resolution compensation may substantially reduce interpretive errors. METHODS AND RESULTS: A prospective multicenter trial was performed recruiting patients with angiographically documented coronary disease (n=96) and group of subjects with a low likelihood of disease (n=88). The uncorrected and attenuation/scatter corrected images were read independently, without knowledge of the patient's clinical data. The detection of >/=50% stenosis was similar using uncorrected perfusion data or with attenuation/scatter correction and resolution compensation (visual or visual plus quantitative analysis), 76% versus 75% versus 78%, respectively (P=NS). The normalcy rate, however, was significantly improved with this new methodology, using either the corrected images (86% vs 96%; P=0.011) or with the corrected data and quantitative analysis (86% vs 97%; P=0.007). The receiver operator characteristic curves were also found to be marginally but not significantly higher with attenuation/scatter correction than with tradition SPECT imaging. However, the ability to detect multivessel disease was reduced with attenuation/scatter correction. Regional differences were also noted, with reduced sensitivity but improved specificity for right coronary lesions using attenuation/scatter correction methodology. CONCLUSIONS: This multicenter trial demonstrates the initial clinical results of a new SPECT perfusion imaging modality incorporating attenuation and scatter correction in conjunction with 99mTc sestamibi perfusion imaging. Significant improvements in the normalcy rate were noted without a decline in overall sensitivity but with a reduction in detection of extensive coronary disease.

Incremental prognostic value of adenosine myocardial perfusion single-photon emission computed tomography in women with suspected coronary artery disease.

Adenosine myocardial perfusion single-photon emission computed tomography (SPECT) is now increasingly used for risk stratification of patients with known or suspected coronary artery disease. However, the incremental prognostic value of this test over clinical and historical information in a large series of women has not been examined. Thus, we studied 923 consecutive women who underwent adenosine technetium (Tc)-99m sestamibi myocardial perfusion SPECT and were followed-up for a mean period of 26+/-8 months. During the follow-up period, 77 hard events (46 cardiac deaths and 31 nonfatal myocardial infarctions) occurred. The results of the perfusion scan significantly risk stratified the population; patients with normal scans had a low rate of nonfatal myocardial infarction and cardiac death (< 1%/year of follow up). Patients with mildly abnormal scans had low cardiac death rates (0.9%/year of follow up); these rates increased as a function of scan abnormality (4.1% and 7.5% mortality per year of follow up in moderate and severely abnormal scans). Cox proportional hazards analysis demonstrated that after adjusting for prior myocardial infarction and diabetes mellitus (the most predictive individual clinical variables [global chi-square=22.5, p <0.001]), as well as heart rate at rest (the most predictive physiologic variable [chi-square=3.8; p=0.05]), the most predictive nuclear variable (summed stress score [chi-square=48.5; p <0.0001]) added significant incremental prognostic information (global chi-square increased from 22.5 to 56.2 [p <0.0001]). In conclusion, adenosine myocardial perfusion SPECT added significant incremental prognostic information to clinical and physiologic variables in women. Normal scans were associated with an excellent prognosis. In contrast, patients with moderately to severely abnormal scans were at a higher risk for future cardiac events.