Coronary CT angiography using 64 detector rows: methods and design of the multi-centre trial CORE-64

Multislice computed tomography (MSCT) for the noninvasive detection of coronary artery stenoses is a promising candidate for widespread clinical application because of its non-invasive nature and high sensitivity and negative predictive value as found in several previous studies using 16 to 64 simultaneous detector rows. A multi-centre study of CT coronary angiography using 16 simultaneous detector rows has shown that 16-slice CT is limited by a high number of nondiagnostic cases and a high false-positive rate. A recent meta-analysis indicated a significant interaction between the size of the study sample and the diagnostic odds ratios suggestive of small study bias, highlighting the importance of evaluating MSCT using 64 simultaneous detector rows in a multi-centre approach with a larger sample size. In this manuscript we detail the objectives and methods of the prospective ""CORE-64"" trial (""Coronary Evaluation Using Multidetector Spiral Computed Tomography Angiography using 64 Detectors""). This multi-centre trial was unique in that it assessed the diagnostic performance of 64-slice CT coronary angiography in nine centres worldwide in comparison to conventional coronary angiography. In conclusion, the multi-centre, multi-institutional and multi-continental trial CORE-64 has great potential to ultimately assess the per-patient diagnostic performance of coronary CT angiography using 64 simultaneous detector rows.

Intraosseous Anesthesia in Hemodynamic Studies in Children with Cardiopathy

Aliman AC, Piccioni MA, Piccioni JL, Oliva JL, Auler Junior JOC - Intraosseous Anesthesia in Hemodynamic Studies in Children with Cardiopathy. Background and objectives: Intraosseous (IO) access has been used with good results in emergency situations, when venous access is not available for fluids and drugs infusion. The objective of this study was to evaluate IO a useful technique for anesthesia and fluids infusion during hemodynamic studies and when peripheral intravascular access is unobtainable. The setting was an university hospital hemodynamics unit, and the subjects were twenty one infants with congenital heart disease enrolled for elective hemodynamic study diagnosis. Methods: This study compared the effectiveness of IO access in relation to IV access for infusion of anesthetics agents (ketamine, midazolann, and fentanyl) and fluids during hemodynamic studies. The anesthetic induction time, procedure duration, anesthesia recovery time, adequate hydration, and IV and IO puncture complications were compared between groups. Results: The puncture time was significantly smaller in IO group (3.6 min) that in IV group (9.6 min). The anesthetic onset time (56.3 second) for the IV group was faster than IO group (71.3 second). No significant difference between groups were found in relation to hydration (IV group, 315.5 mL vs IO group, 293.2 mL), and anesthesia recovery time (IO group, 65.2 min vs IV group, 55.0 min). The puncture site was reevaluated after 7 and 15 days without signs of infection or other complications. Conclusions: Results showed superiority for IO infusion when considering the puncture time of the procedure. Due to its easy manipulation and efficiency, hydration and anesthesia by IO access was satisfactory for hemodynamic studies without the necessity of other infusion access.

An Inhalation Chamber Model for Controlled Studies of Tobacco Smoke Toxicity in Rodents

Introduction: Smoking is a serious worldwide public health problem. Animal models act as a bridge between laboratory and human studies. The models applied are difficult to reproduce because of the use of different types of inhalation chambers and mainly because of the lack of continuous monitoring of smoke concentration. Objective: To develop an inhalation chamber for rats (with only the nose exposed) in which the amount of carbon monoxide (CO) can be maintained and monitored constantly. Material and methods: Male Wistar rats weighing 250 g were exposed to 50 ppm CO produced by the smoke from a filter-free cigarette. The animals were submitted to a single 2-h exposure and then sacrificed at 0, 4, 24 and 48 h. The control group was left restrained inside the small perpendicular chambers, receiving only 5 L/min of compressed air. Results: The model was able to increase HbCO levels immediately after the end of exposure (p < 0.001). with a decrease being observed from 2 h onwards when compared to the levels of the control group. Plasma cotinine increased immediately after exposure, and showed still detectable levels at 2 and 4 h (p < 0.05). Conclusion: We conclude that the presented inhalation chamber system is able to maintain a controlled CO concentration in a model in which small animals are exposed to the inhalation of cigarette smoke, permitting well-controlled studies, as well as investigations involving other toxic gases and air pollutants. (C) 2008 SEPAR. Published by Elsevier Espana, S.L. All rights reserved.

Synthetic nanoemulsion resembling a protein-free model of 7-ketocholesterol containing low density lipoprotein: In vitro and in vivo studies

7-ketocholesterol (7-KC) differs from cholesterol by a functional ketone group at C7. It is an oxygenated cholesterol derivative (oxysterol), commonly present in oxidized low-density lipoprotein (LDL). Oxysterols are generated and participate in several physiologic and pathophysiologic processes. For instance, the cytotoxic effects of oxidized LDL have been widely attributed to bioactive compounds like oxysterols. The toxicity is in part due to 7-KC. Here we aimed to demonstrate the possibility of incorporating 7-KC into the synthetic nanoemulsion LDE, which resembles LDL in composition and behavior. This would provide a suitable artificial particle resembling LDL to study 7-KC metabolism. We were able to incorporate 7-KC in several amounts into LDE. The incorporation was evaluated and confirmed by several methods, including gel filtration chromatography, using radiolabeled lipids. The incorporation did not change the main lipid composition characteristics of the new nanoparticle. Particle sizes were also evaluated and did not differ from LDE. In vivo studies were performed by injecting the nanoemulsion into mice. The plasma kinetics and the targeted organs were the same as described for LDE. Therefore, 7-KC-LDE maintains composition, size and some functional characteristics of LDE and could be used in experiments dealing with 7-ketocholesterol metabolism in lipoproteins.

Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Methods We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Results Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) < 18.5 kg/m(2) (2.13, 1.75-2.58) and reduced for BMI > 25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI >= 30 kg/m(2) (0.43, 0.33-0.57), compared with BMI > 18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI < 18.5 kg/m(2) was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m(2) was present only in smokers and drinkers. Conclusions In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies.

Low human papillomavirus prevalence in head and neck cancer: results from two large case-control studies in high-incidence regions

Background Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA) prevalence as well as the association between serological response to HPV infection and HNSCC in two distinct populations from Central Europe (CE) and Latin America (LA). Methods Cases (n = 2214) and controls (n = 3319) were recruited from 1998 to 2003, using a similar protocol including questionnaire and blood sample collection. Tumour DNA from 196 fresh tissue biopsies was analysed for multiple HPV types followed by an HPV type-specific polymerase chain reaction (PCR) protocol towards the E7 gene from HPV 16. Using multiplex serology, serum samples were analysed for antibodies to 17 HPV types. Statistical analysis included the estimation of adjusted odds ratios (ORs) and the respective 95% confidence intervals (CIs). Results HPV16 E7 DNA prevalence among cases was 3.1% (6/196), including 4.4% in the oropharynx (3/68), 3.8% in the hypopharynx/larynx (3/78) and 0% among 50 cases of oral cavity carcinomas. Positivity for both HPV16 E6 and E7 antibodies was associated with a very high risk of oropharyngeal cancer (OR = 179, 95% CI 35.8-899) and hypopharyngeal/laryngeal cancer (OR = 14.9, 95% CI 2.92-76.1). Conclusions A very low prevalence of HPV DNA and serum antibodies was observed among cases in both CE and LA. The proportion of head and neck cancer caused by HPV may vary substantially between different geographical regions and studies that are designed to evaluate the impact of HPV vaccination on HNSCC need to consider this heterogeneity.

Ventilation Distribution Studies Comparing Technegas and ""Gallgas"" Using (68)GaCl(3) as the Label

Ventilation distribution can be assessed by SPECT with Technegas. This study was undertaken in piglets with different degrees of ventilation inhomogeneity to compare PET using (68)Ga-labeled pseudogas or ""Gallgas"" with Technegas. Methods: Twelve piglets were studied in 3 groups: control, lobar obstruction, and diffuse airway obstruction. Two more piglets were assessed for lung volume (functional residual capacity). Results: In controls, SPECT and PET images showed an even distribution of radioactivity. With lobar obstruction, the absence of ventilation of the obstructed lobe was visible with both techniques. In diffuse airway obstruction, SPECT images showed an even distribution of radioactivity, and PET images showed more varied radioactivity over the lung. Conclusion: PET provides detailed ventilation distribution images and a better appreciation of ventilation heterogeneity. Gallgas with PET is a promising new diagnostic tool for the assessment of ventilation distribution.

Quantitative myocardial contrast echocardiography during pharmacological stress for diagnosis of coronary artery disease: a systematic review and meta-analysis of diagnostic accuracy studies

Aims We conducted a meta-analysis to evaluate the accuracy of quantitative stress myocardial contrast echocardiography (MCE) in coronary artery disease (CAD). Methods and results Database search was performed through January 2008. We included studies evaluating accuracy of quantitative stress MCE for detection of CAD compared with coronary angiography or single-photon emission computed tomography (SPECT) and measuring reserve parameters of A, beta, and A beta. Data from studies were verified and supplemented by the authors of each study. Using random effects meta-analysis, we estimated weighted mean difference (WMD), likelihood ratios (LRs), diagnostic odds ratios (DORs), and summary area under curve (AUC), all with 95% confidence interval (0). Of 1443 studies, 13 including 627 patients (age range, 38-75 years) and comparing MCE with angiography (n = 10), SPECT (n = 1), or both (n = 2) were eligible. WMD (95% CI) were significantly less in CAD group than no-CAD group: 0.12 (0.06-0.18) (P < 0.001), 1.38 (1.28-1.52) (P < 0.001), and 1.47 (1.18-1.76) (P < 0.001) for A, beta, and A beta reserves, respectively. Pooled LRs for positive test were 1.33 (1.13-1.57), 3.76 (2.43-5.80), and 3.64 (2.87-4.78) and LRs for negative test were 0.68 (0.55-0.83), 0.30 (0.24-0.38), and 0.27 (0.22-0.34) for A, beta, and A beta reserves, respectively. Pooled DORs were 2.09 (1.42-3.07), 15.11 (7.90-28.91), and 14.73 (9.61-22.57) and AUCs were 0.637 (0.594-0.677), 0.851 (0.828-0.872), and 0.859 (0.842-0.750) for A, beta, and A beta reserves, respectively. Conclusion Evidence supports the use of quantitative MCE as a non-invasive test for detection of CAD. Standardizing MCE quantification analysis and adherence to reporting standards for diagnostic tests could enhance the quality of evidence in this field.

Synthesis, spectroscopic characterization, DFT studies and biological assays of a novel gold(I) complex with 2-mercaptothiazoline

A new gold(I) complex with 2-mercaptothiazoline (MTZ) with the coordination formula [AuCN(C(3)H(5)NS(2))] was synthesized and characterized by chemical and spectroscopic measurements, OFT studies and biological assays. Infrared (IR) and (1)H, (13)C and (15)N nuclear magnetic resonance (NMR) spectroscopic measurements indicate coordination of the ligand to gold(I) through the nitrogen atom. Studies based on OFT confirmed nitrogen coordination to gold(I) as a minimum of the potential energy surface with calculations of the hessians showing no imaginary frequencies. Thermal decomposition starts at temperatures near 160 degrees C, leading to the formation of Au as the final residue at 1000 degrees C. The gold(I) complex with 2-mercaptothiazoline (Au-MTZ) is soluble in dimethyl sulfoxide (DMSO), and is insoluble in water, methanol, ethanol, acetonitrile and hexane. The antibacterial activities of the Au-MTZ complex were evaluated by an antibiogram assay using the disc diffusion method. The compound showed an effective antibacterial activity against Staphylococcus aureus (Gram-positive) and Escherichia coli and Pseudomonas aeruginosa (Gram-negative) bacterial cells. Biological analysis for evaluation of the cytotoxic effect of the Au-MTZ complex was performed using HeLa cells derived from human cervical adenocarcinoma. The complex presented a potent cytotoxic activity, inducing 85% of cell death at a concentration of 2.0 mu mol L(-1). (C) 2011 Elsevier Ltd. All rights reserved.

Acute alterations in anorectal manometry induced by proximal and distal sphincterotomy. Experimental studies on piglets

Anal incontinence causes psychological, social and adaptive troubles prejudicial to the quality of life both in children and adults. Therefore, the detailed knowledge of its causes and the improvement of diagnostic and therapeutic methods increase the possibilities of a more adequate social life to patients with congenital anomalies or sphincteric lesions or degenerations. In this work, a manometric study was developed through an experimental model so as to analyze alterations in behavior of muscle groups responsible for the anorectal sphincteric mechanism, previous to and after proximal and distal lesions. Twenty-two pigs aged between 25 and 30 days, weighing 5-7 kg, were randomly divided into two groups. They were submitted to lesions of different levels in the anorectal muscle. The animals were studied by anorectal manometry (rectoanal inhibitory reflex and vector volume) before and after the lesions. The Student t test and the Wilcoxon test were applied for the statistical analyses, considered p <= 0.05. The proximal lesion preserved sphincter relaxation, retarding its closure [speed of relaxation recovery 4.35 +/- 2.10 vs. 2.70 +/- 1.32 mm/s (p = 0.001)], but it reduced the maximum pressure [62.45 +/- 20.02 vs. 40.36 +/- 12.59 mmHg (p = 0.004)] and vector volume [2,749 +/- 921 vs. 1,591 +/- 1,379 mmHg(2)cm (p = 0.005)]. There was an increment in the high-pressure zone [5.09 +/- 1.04 vs. 6.36 +/- 1.50 mm (p = 0.005)], but the asymmetry percentage and the sphincter length were maintained. The distal lesion did not alter the rectoanal inhibitory reflex, the high-pressure zone length, the asymmetry percentage, or the vector volume. Nevertheless, the sphincter length increased [11.82 +/- 2.82 vs. 14.09 +/- 2.39 mm (p = 0.022)] and the maximum pressure decreased [60.55 +/- 22.05 vs. 40.91 +/- 13.41 mmHg (p = 0.004)]. The alterations observed due to proximal lesion of the anorectal sphincter suggest a direct and more important interference of the levator ani muscle in the function of the sphincteric musculature than that caused by the distal lesion.

Evaluation of computational methods for the reconstruction of HLA haplotypes

Human leukocyte antigen (HLA) haplotypes are frequently evaluated for population history inferences and association studies. However, the available typing techniques for the main HLA loci usually do not allow the determination of the allele phase and the constitution of a haplotype, which may be obtained by a very time-consuming and expensive family-based segregation study. Without the family-based study, computational inference by probabilistic models is necessary to obtain haplotypes. Several authors have used the expectation-maximization (EM) algorithm to determine HLA haplotypes, but high levels of erroneous inferences are expected because of the genetic distance among the main HLA loci and the presence of several recombination hotspots. In order to evaluate the efficiency of computational inference methods, 763 unrelated individuals stratified into three different datasets had their haplotypes manually defined in a family-based study of HLA-A, -B, -DRB1 and -DQB1 segregation, and these haplotypes were compared with the data obtained by the following three methods: the Expectation-Maximization (EM) and Excoffier-Laval-Balding (ELB) algorithms using the arlequin 3.11 software, and the PHASE method. When comparing the methods, we observed that all algorithms showed a poor performance for haplotype reconstruction with distant loci, estimating incorrect haplotypes for 38%-57% of the samples considering all algorithms and datasets. We suggest that computational haplotype inferences involving low-resolution HLA-A, HLA-B, HLA-DRB1 and HLA-DQB1 haplotypes should be considered with caution.

Validation of non-fluorescent methods to reliably detect acrosomal and plasma membrane integrity of common marmoset (Callithrix jacchus) sperm

Simple, rapid and stable sperm evaluation methods which have been optimized for common marmoset (Callithrix jacchus) are critical for studies involving collection and evaluation of sperm in the field. This is particularly important for new species groups such as Callitrichidae where the sperm have been little studied. Of this family, C jacchus is the best known, and has been chosen as a model species for other members of the genus Callithrix. The fundamental evaluation parameters for sperm of any species are viability and acrosomal status. Semen samples were collected by penile vibratory stimulation. To evaluate sperm plasma membrane integrity, Eosin-Nigrosin was tested here for the common marmoset sperm to be used under field conditions. Further, a non-fluorescent stain for acrosome, the ""Simple"" stain, developed for domestic and wild cats, was tested on common marmoset sperm. This was compared with a fluorescent staining, Fluorescein isothiocyanate-Pisum sativum agglutinin (FITC-PSA), routinely used and validated for common marmoset at the German Primate Centre to evaluate acrosomal integrity. Results obtained with the ""Simple"" stain showed a marked differentiation between sperm with intact and non-intact acrosome both with and without ionophore treatment and closely correlated with results obtained with FITC-PSA. Temperature had no effect on the results with the ""Simple"" stain and the complete processing is simple enough to be carried out under field conditions. These findings indicated that the ""Simple"" stain and Eosin-Nigrosin provide rapid and accurate results for C. jacchus sperm and that those methods can be reliably used as field tools for sperm evaluation for this species. (c) 2008 Elsevier Inc. All rights reserved.

Pooled analysis of recent studies on magnetic fields and childhood leukaemia

BACKGROUND: Previous pooled analyses have reported an association between magnetic fields and childhood leukaemia. We present a pooled analysis based on primary data from studies on residential magnetic fields and childhood leukaemia published after 2000. METHODS: Seven studies with a total of 10 865 cases and 12 853 controls were included. The main analysis focused on 24-h magnetic field measurements or calculated fields in residences. RESULTS: In the combined results, risk increased with increase in exposure, but the estimates were imprecise. The odds ratios for exposure categories of 0.1-0.2 mu T, 0.2-0.3 mu T and >= 0.3 mu T, compared with <0.1 mu T, were 1.07 (95% Cl 0.81-1.41), 1.16 (0.69-1.93) and 1.44 (0.88-2.36), respectively. Without the most influential study from Brazil, the odds ratios increased somewhat. An increasing trend was also suggested by a nonparametric analysis conducted using a generalised additive model. CONCLUSIONS: Our results are in line with previous pooled analyses showing an association between magnetic fields and childhood leukaemia. Overall, the association is weaker in the most recently conducted studies, but these studies are small and lack methodological improvements needed to resolve the apparent association. We conclude that recent studies on magnetic fields and childhood leukaemia do not alter the previous assessment that magnetic fields are possibly carcinogenic. British Journal of Cancer (2010) 103, 1128-1135. doi: 10.1038/sj.bjc.6605838 www.bjcancer.com (c) 2010 Cancer Research UK

Ciprofibrate quantification in human plasma by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry for pharmacokinetic studies

A rapid, sensitive and specific method for quantifying ciprofibrate in human plasma using bezafibrate as the internal standard (IS) is described. The sample was acidified prior extraction with formic acid (88%). The analyte and the IS were extracted from plasma by liquid-liquid extraction using an organic solvent (diethyl ether/dichloromethane 70/30 (v/v)). The extracts were analyzed by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). Chromatography was performed using Genesis C18 4 mu m analytical column (4.6 x 150 mm i.d.) and a mobile phase consisting of acetonitrile/water (70/30, v/v) and 1 mM acetic acid. The method had a chromatographic run time of 3.4 min and a linear calibration curve over the range 0.1-60 mu g/mL (r > 0.99). The limit of quantification was 0.1 mu g/mL. The intra- and interday accuracy and precision values of the assay were less than 13.5%. The stability tests indicated no significant degradation. The recovery of ciprofibrate was 81.2%, 73.3% and 76.2% for the 0.3, 5.0 and 48.0 ng/mL standard concentrations, respectively. For ciprofibrate, the optimized parameters of the declustering potential, collision energy and collision exit potential were -51 V, -16 eV and -5 V, respectively. The method was also validated without the use of the internal standard. This HPLC-MS/MS procedure was used to assess the bioequivalence of two ciprofibrate 100 mg tablet formulations in healthy volunteers of both sexes. The following pharmacokinetic parameters were obtained from the ciprofibrate plasma concentration vs. time curves: AUC(last), AUC(0-168 h), C(max) and T(max). The geometric mean with corresponding 90% confidence interval (CI) for test/reference percent ratios were 93.80% (90% CI = 88.16-99.79%) for C(max), 98.31% (90% CI = 94.91-101.83%) for AUC(last) and 97.67% (90% CI = 94.45-101.01%) for AUC(0-168 h). Since the 90% Cl for AUC(last), AUC(0-168 h) and C(max) ratios were within the 80-125% interval proposed by the US FDA, it was concluded that ciprofibrate (Lipless (R) 100 mg tablet) formulation manufactured by Biolab Sanus Farmaceutica Ltda. is bioequivalent to the Oroxadin (R) (100 mg tablet) formulation for both the rate and the extent of absorption. (C) 2011 Published by Elsevier B.V.

Comparison of two methods for collecting free-living ticks in the Amazonian forest

In the present study, we compared 2 methods for collecting ixodid ticks on the verges of animal trails in a primary Amazon forest area in northern Brazil. (i) Dragging: This method was based on passing a 1-m(2) white flannel over the vegetation and checking the flannel for the presence of caught ticks every 5-10 m. (ii) Visual search: This method consisted of looking for guesting ticks on the tips of leaves of the vegetation bordering animal trails in the forest. A total of 103 adult ticks belonging to 4 Amblyomma species were collected by the visual search method on 5 collecting dates, while only 44 adult ticks belonging to 3 Amblyomma species were collected by dragging on 5 other collecting dates. These values were statistically different (Mann-Whitney Test, P = 0.0472). On the other hand, dragging was more efficient for subadult ticks, since no larva or nymph was collected by visual search, whereas 18 nymphs and 7 larvae were collected by dragging. The visual search method proved to be suitable for collecting adult ticks in the Amazon forest: however, field studies should include a second method, such as dragging in order to maximize the collection of subadult ticks. Indeed, these 2 methods can be performed by a single investigator at the same time, while he/she walks on an animal trail in the forest. (C) 2010 Elsevier GmbH. All rights reserved.