Biodegradability of the antioxidant diaryl-p-phenylene diamine using a modified inherent biodegradation method at an environmentally relevant concentration.

The chemical product diaryl-p-phenylene diamine (DAPD), produced by The Goodyear Tire & Rubber Company as POLYSTAY 100 (CAS 68953-84-4), is employed as an antidegradant in polymers used in tires and industrial rubber products. Previous evaluations pertaining to the ecological fate of DAPD indicated a lack of biodegradative activity in aquatic media. In order to further pursue the biodegradation potential of DAPD, it was deemed necessary to enhance the sensitivity of the aquatic biodegradation assay through (a) employment of a radiotracer of the test substance, and (b) optimisation of conditions for achieving maximal solubilisation of test material in the aquatic media of the incubation vessels. Test vessels were prepared according to the OECD ready biodegradability test guidelines, with DAPD added on silica gel at concentrations of 10 or 100 µg L(-1), together with a surfactant to aid solubilisation. After 63 d incubation up to 37% mineralisation was measured and up to 29% of the applied radioactivity was incorporated into cell biomass. Also, after 28 d no DAPD could be measured in solution by radio-TLC and HPLC-MS. These three results demonstrate that the antioxidant DAPD undergoes microbiologically mediated biodegradation and is highly unlikely to persist in the environment.

MSCT guided sizing of the Edwards Sapien XT TAVI device: impact of different degrees of oversizing on clinical outcome.

AIMS: Prospective data on the usage of 3-dimensional imaging based annulus sizing on the outcome of TAVI is not available yet and there is general uncertainty about the optimal degree of oversizing. In the current study we therefore assessed a 3-D MSCT guided over-sizing approach and evaluated the clinical outcome of different degrees of oversizing. METHODS: TAVI-size-selection was done using systolic MSCT-annulus cross-sectional-area (CSA) measurements in 107 patients with severe aortic stenosis with the goal to oversize the 3rd generation balloon expandable Edwards Sapien XT (ESTV) device in relation to the native aortic annulus CSA. RESULTS: Among different degrees of oversizing there were no differences in the occurrence of stroke, myocardial infarction and death. No aortic injuries were observed. The overall rate of >mild postprocedural aortic regurgitation (PAR) was 7.6%. Increasing oversizing ratios are associated with lower rates of >mild PAR (r = -0.236, p<0.02) with the lowest rate of >mild PAR in patients with area based oversizing ratios >25% and the highest rate in patients with oversizing ratios <15% (0% vs. 15.8%, p<0.02). The rate of postprocedural permanent pacemakers tended to be lower in patients with <15% oversizing compared to those with >25% oversizing (5.3 vs. 16.7%, p<0.23). CONCLUSIONS: MSCT guided ESTV-device sizing is safe and is associated with significantly lower than previously reported rates for PAR. A device/annulus oversizing ratio of 15-25% based on area and 7-12% based on mean diameter appears to provide the best risk-benefit ratio in terms of PAR reduction and conduction disorders.

Cryoballoon in atrial fibrillation ablation.

Encouraging results of ablation therapy in patients with paroxysmal atrial fibrillation (AF) have prompted changes in professional practice guidelines. The most recent European guidelines have suggested that ablation might be offered as first-line therapy in selected patients. Cryoballoon ablation is a promising technology in interventional AF therapy. Two different sizes of the cryoballoon are currently available: a smaller (23 mm) and a larger (28 mm) balloon relative to the ostial diameter of the pulmonary veins. New tools, the circular mapping catheter and the use of intracardiac echocardiography, provide important periprocedural information. A meta-analysis of previous studies revealed outcome data with an AF-free survival rate of 72.83% at the 1-year follow-up in paroxysmal AF patients undergoing cryoballoon ablation. The most frequent, but reversible complication is phrenic nerve palsy with reported incidences up to 10%. All efforts must be taken to overcome this limitation, since the overall major complication rate tends to be lower in cryoballoon compared to radiofrequency ablation. In persistent AF, reported results in cryoballoon ablation had a limited success rate below 50% after a single procedure. A double balloon approach using both cryoballoon sizes might overcome some of the limitations in persistent AF. Prospective data and randomized studies are required. This article outlines the current status of cryoballoon technology in AF ablation therapy.

The cost of medical management of pulmonary nontuberculous mycobacterial disease in Ontario, Canada.

Treatment of pulmonary nontuberculous mycobacterial (NTM) infection is complex, requiring multiple antibiotics and a prolonged treatment course. We determined the monthly cost of treating patients with pulmonary NTM infections in our clinic, a tertiary care centre in Toronto, Ontario, Canada. We reviewed records of a single clinic at the University Health Network (Toronto) for all patients with pulmonary NTM isolates. Pharmacological and nonpharmacological treatment costs were calculated using a number of Canadian references. 172 patients were reviewed, 91 of whom were treated pharmacologically. The median total duration and cost per treated patient were 14 months (interquartile range (IQR) 9-23 months) and CAD 4,916 (IQR CAD 2,934-9,063), respectively. Median monthly drug treatment cost was CAD 321 (IQR CAD 254-458) for all patients, CAD 289 (IQR CAD 237-341) for patients receiving exclusively oral antibiotics and CAD 1,161 (IQR CAD 795-1,646) for patients whose treatment included i.v. antibiotics. The most costly oral regiment consisted of a fluroquinolone, macrolide and rifampin. In multivariable analysis, Mycobacterium abscessus infection, i.v. therapy and Mycobacterium xenopi infection were all associated with increased monthly treatment costs. The direct medical costs of NTM infections are substantial. Less expensive alternative therapies might be most helpful for M. abscessus infection and when i.v. antibiotics are deemed necessary.

A 21-year-old man with systemic-onset juvenile rheumatoid arthritis, cough and progressive dyspnea.

Primary or nonobstructive, endogenous lipoid pneumonia is a rare clinical entity usually associated with an underlying systemic disease. The present report describes a case involving a 21-year-old man with systemic-onset juvenile rheumatoid arthritis who developed primary endogenous lipoid pneumonia. Multiple treatment regimens were attempted; however, definitive management was only achieved through double-lung transplantation.

[Dual-source cardiac CT imaging with improved temporal resolution: Impact on image quality and analysis of left ventricular function]. / Dual-source-Computertomographie des Herzens: Bildqualität und Funktionsanalyse bei verbesserter zeitlicher Auflösung.

In a newly developed dual-source computed tomography system (DSCT) the relation of heart rate and image quality and the possible advantages of the system's superior temporal resolution in the evaluation of left ventricular parameters as compared to results of cardiac magnetic resonance imaging (MRI) were assessed. Coronary CT angiography was performed using a DSCT (Somatom Defintion, Siemens Medical Solutions, Forchheim, Germany) in 21 patients (mean age 62+/-8; 15 male, 6 female). Image quality of the coronary arteries, the heart valves, and the left ventricular myocardium was assessed using a three-point grading scale. Ten of these patients also underwent cardiac MRI for the assessment of left ventricular function, using a SSFP (steady-state free precession) sequence. Left ventricular ejection fractions (LV-EF), the end-systolic volumes (ESV), and the end-diastolic volumes (EDV) were measured employing MRI and DSCT datasets. The image quality ratings for the coronary arteries at the optimal reconstruction interval were diagnostic even in patients with high heart rates (1.42+/-0.49). Analysis of global LV function using DSCT quantified from CTA datasets showed a good correlation with results of cardiac MRI [EF: r=0.75 (p=0.01); ESV: r=0.72 (p=0.19); EDV: r=0.71 (p=0.02)]. The dual-source CT system offers robust image quality of the coronary arteries, independent of the heart rate, and provides combined diagnostic imaging of coronary arteries, the heart valves, the myocardium, and the global left ventricular function.

Visual quality determines the direction of neural repetition effects.

One ubiquitous finding in functional magnetic resonance imaging studies is that repeated stimuli elicit lower responses than novel stimuli. In apparent contradiction, some studies have reported the exact opposite effect--greater responses to repeated than novel stimuli--in many of the same brain regions. Interestingly, these latter enhancement effects are typically obtained when stimuli have been degraded. To explore this observation, the present study examines the degree to which visual quality mediates repetition effects in a stimulus-selective ventral visual area. Subjects were presented with grayscale photographs of scenes that were either near or substantially above visual threshold, as determined by calibrating image contrast to behavioral performance. The presentation of 2 identical high-contrast scenes elicited lower blood oxygen level-dependent (BOLD) responses than the presentation of 2 different high-contrast scenes (repetition attenuation). Conversely, the presentation of 2 identical low-contrast scenes elicited greater BOLD responses than the presentation of 2 different low-contrast scenes (repetition enhancement). Neurophysiological studies suggest that repetition attenuation in ventral visual areas may reflect the reactivation of perceptual representations that have become sparse and selective as a result of prior experience, whereas repetition enhancement may reflect spared access to existing representations by severely degraded input.

[Prediction of serious cardiovascular events by determining coronary artery calcification measured by multi-slice computed tomography]. / Prädiktion kardiovaskulärer Ereignisse durch Koronarkalkbestimmung mit der Mehrzeilen-Computertomographie.

BACKGROUND: The efficacious prophylaxis of myocardial infarction requires an accurate identification of patients at risk. Conventional risk stratification is often insufficient for this. We therefore examined the predictive value of coronary calcifications for future cardiovascular events. METHODS: We determined the extent of coronary calcification by multi-slice computed tomography in 924 patients (443 men, 481 women, aged 59.4 +/- 18.7 years) after coronary artery disease had been excluded by coronary angiography. To quantify coronary calcifications the volume score was calculated. After an observation period of 36 months was calculated the incidence of coronary revascularisation, myocardial infarction, and cardiac death. RESULTS: During the observation period the event rates for coronary revascularization (5.4 %/ year vs. 2.9 %/ year), myocardial infarction (3.8 %/ year vs. 1.8 %/ year), and cardiac death (2.1 %/ year vs. 1.0 %/ year) in patients with volume scores above the 75th percentile were significantly higher compared to the total study group. Correspondingly the scores in patients with revascularization (397 +/- 187), myocardial infarction (412 +/- 176), and cardiac death (422 +/- 184) were significantly higher compared to patients without cardiovascular events (218 +/- 167). In addition future cardiovascular events were excluded in patients without coronary calcifications. CONCLUSIONS: By determining coronary calcifications it was possible to identify patients at risk for myocardial infarction could be identified. Future cardiovascular events could not be observed in patients without coronary calcifications.

[Evaluating multislice computed tomography for imaging coronary atherosclerosis]. / Evaluierung der Mehrzeilendetektorcomputertomographie zur Darstellung der koronaren Atherosklerose.

PURPOSE: The purpose of this study was the evaluation of multidetector-row computed tomography (MDCT) for the assessment of atherosclerotic coronary artery vessel wall changes. METHODS: In an ex vivo study, 17 human hearts were scanned with MDCT and results were compared to histopathology. Morphologic imaging criteria of MDCT for various plaque-types were developed. In a following in vivo study, 94 coronary MDCT angiograms (MDCTA) of patients with suspected coronary artery disease (CAD) were reviewed retrospectively, assessing the diagnostic value of the coronary MDCTA, and determining the number and correlations of the various plaques types as described in the ex vivo study. Additionally, volumetry of calcified and noncalcified plaque components was performed. RESULTS: In the ex vivo study, MDCT showed a high sensitivity for calcified and non-calcified plaques. Comparing the results with histopathology, characteristic image criteria could be determined for lipid-rich, fibrous and calcified plaque components. Reviewing the contrastenhanced in-vivo MDCT coronary angiographies, presence of noncalcified plaques was proven in 38% of the patients. In 5 patients with a calcium score of 0, presence of coronary atherosclerosis was proven in the contrastenhanced scan. CONCLUSIONS: MDCT is able to differentiate various plaque components in an ex vivo setting as well as invivo. Contrastenhanced MDCT of the coronary arteries allows for the detection of noncalcified plaques. In vivo volumetry of noncalcified plaques is feasible.

[Technique and possibilities of cardiac computed tomography]. / Kardiale Mehrzeilen-Computertomographie. Koronarangiographie--ein Auslaufmodell?

Electron beam computed tomography no longer has a role to play in Germany. In contrast, multidetector spiral CT has great potential for replacing some coronary catheter studies, in particular for the exclusion of coronary artery disease, and this in particular since the forthcoming introduction of a 64-slice MDCT scanner promises a further improvement in temporal and special resolution. Currently, however it is no alternative to invasive angiography, since quantification of coronary stenoses is not possible; nor can a diagnostic evaluation be made in the presence of coronary calcifications or intracoronary stents. In particular, however, before applying CT angiography to the heart, the patient groups that can benefit from this method must be defined, especially in light of the fact that radiation exposure is three times as high as with diagnostic coronary catheterization.

[Coronary calcifications and the diagnosis of coronary artery disease]. / Screeningmethode bei asymptomatischen Risikopatienten. Kalkscore als früher Marker der Koronarsklerose.

Coronary calcium is a sensitive marker of coronary atherosclerosis, even at an early stage. With the aid of multislice computed tomography, noninvasive visualization of the microcalcification is possible. This enables the identification of asymptomatic patients at risk of developing future cardiovascular disease, and the initiation of effective preventive measures. In addition, in symptomatic patients, CT angiography with calcium scoring is of high negative predictive value in the exclusion of coronary artery disease.

[Detection and characterization of atherosclerotic coronary plaques with multislice spiral computed tomography]. / Kardiale Risikostratifizierung: Den atherosklerotischen Plaque im Blick.

Provided that adequate image quality is achieved, contrast-enhanced multislice spiral computed tomography enables the identification and characterisation of calcified and non-calcified coronary plaques. This is a major advance in the non-invasive assessment of coronary atherosclerosis that promises to open up new opportunities for a better understanding and risk stratification of this condition, with visualization of non-calcified hypodense lesions in particular appearing to be of prognostic importance. Current limitations of the technique relating mainly to temporal and spatial resolution may be eliminated by the introduction of a new generation of scanners enabling 64 slices and more.

Non-invasive intravenous coronary angiography using electron beam tomography and multislice computed tomography.

BACKGROUND: Electron beam computed tomography (EBCT) and multislice computed tomography (MSCT) are both suitable for non-invasive identification of coronary stenoses. OBJECTIVE: To compare intravenous coronary EBCT angiography (EBCTA) and MSCT angiography (MSCTA) with regard to image quality and diagnostic accuracy. METHODS: EBCTA was done using an Imatron C-150 XP scanner in 101 patients following a standard protocol (slice thickness 3 mm, overlap 1 mm, acquisition time 100 ms, prospective ECG trigger). For MSCTA in a different set of 91 patients (using a Siemens Somatom Plus4VZ scanner), the whole volume of the heart was covered in a spiral technique by four simultaneous detector rows. Using retrospective ECG gating, the raw data were reconstructed in (mean (SD)) 215 (12) axial slices acquired in diastole (slice thickness 1.25 mm, overlap 0.5 mm, acquisition time 250 ms/slice). RESULTS: With EBCTA, 76% of predetermined coronary segments in a nine segment model could be assessed with diagnostic image quality, and with MSCTA, 82%. A low contrast to noise ratio with EBCTA, and the presence of motion artefacts with MSCTA were the main reasons for inadequate image quality. Using conventional angiography as the gold standard, 77% of stenoses of > 50% could be identified correctly with EBCTA and 82% with MSCTA. Significant stenoses were correctly ruled out in 93% of segments with EBCTA, and in 96% of segments with MSCTA. The average contrast to noise ratio was higher with MSCTA than with EBCTA (9.4 v 6.5; p < 0.001). CONCLUSIONS: EBCTA and MSCTA show similarly high levels of accuracy for determining and ruling out significant coronary artery stenoses. MSCTA is capable of providing good image quality in more coronary segments than EBCTA because of its better contrast to noise ratio and higher spatial resolution. Motion artefacts seen at heart rates of > 75 beats/min and a higher radiation exposure are the main limitations of MSCTA.

[Detection of coronary calcinosis with multislice spiral computerized tomography: an alternative to electron beam tomography]. / Detektion von Koronarkalk mit der Mehrschicht-Spiral-Computertomographie: Eine Alternative zur Elektronenstrahltomographie.

Electron-beam CT (EBT) has been used for years as the gold standard to quantify coronary artery calcification as a marker of coronary atherosclerosis. With the introduction of Multi-Slice Spiral CT (MSCT) technology in 1999, EBT is now challenged in the determination of coronary calcium. The aim of this study was to determine the diagnostic accuracy of MSCT for the assessment of coronary calcium, comparing this new technique to EBT. The study population consisted of 54 male patients, aged 58 +/- 11 years with suspected coronary artery disease. For EBT, 40 axial slices (scan time = 100 ms, slice thickness = 3 mm) were acquired in one breath-hold (35 +/- 5 s) using an ECG-trigger at 80% of the RR interval. For MSCT, simultaneous acquisition of four axial slices (scan time = 250 ms, slice thickness = 2.5 mm) allowed the entire heart (40 slices) to be covered in one breath-hold (25 +/- 5 s) using a prospective ECG-trigger (R--450 ms). For quantification of coronary calcium the Agatston and the Volumetric calcium score (VCS) were applied. Mean Agatston score of the study group was calculated as 88 +/- 111 (median = 45), which is between the 25th and 75th age-corrected percentile of asymptomatic patients. For the Volumetric calcium score, number of lesions, calcium mass and density, no statistical difference was found between both imaging modalities. Agatston and Volumetric calcium score were statistically different between and within both scans. Mean variability of VCS of the two methods was calculated as 24% and was in the range of repeated EBT studies (14-44.9%). The Multi-Slice Spiral CT scanner is equivalent to EBT for the determination of coronary calcium and can, therefore, be used for calcium screening. Using a prospective ECG-trigger technique, the application of the Agatston method delivers statistically different results in comparison to EBT. With the application of the spiral mode technique, retrospective ECG-trigger and thinner slice thickness, further improvement in variability can be expected, thus allowing for follow-up studies to determine progression or regression of atherosclerosis with high accuracy.

Usefulness of calcium scoring using electron beam computed tomography and noninvasive coronary angiography in patients with suspected coronary artery disease.

The aim of this study was to investigate the reliability of calcium scoring (CS) and electron beam computed tomographic angiography (EBCTA) as a noninvasive tool in the diagnosis of coronary artery disease (CAD): 93 consecutive patients (aged 59 +/- 9 years) with symptoms suspicious for CAD underwent CS. In 87 of these subjects, an additional EBCTA investigation was performed. Using receiver-operating characteristic curve analysis, we determined a calcium score cut point providing an overall sensitivity of 80% and a specificity of 72% in detecting patients with CAD. For clinical purposes the use of cut points is difficult. We therefore determined score ranges providing >80% specificity (high score range) and >85% sensitivity (low score range) and determined the scores between these ranges as equivocal borderline scores. Calculated on a per-segment basis in assessable proximal and midcoronary segments, the sensitivity for detecting coronary stenoses >50% was 78%, and the specificity was 93%. Thus, 32 of 44 patients with significant CAD and 24 of 49 patients without CAD were correctly classified. The combination of CS and EBCTA predicted CAD in 77% (72 of 93) of patients. No or low calcium scores provided high specificity for ruling out CAD. The addition of EBCTA in those patients improved sensitivity. In patients with high calcium scores, accuracy of EBCTA was not significantly different from CS alone (72% vs 83%), whereas in patients with borderline scores it was significantly superior (80% vs 58%, p <0.03). Thus, the complementary use of CS and EBCTA appears beneficial, particularly in patients with borderline scores, and could improve sensitivity in the low score range. In the presence of high scores, no major diagnostic gain from an additional EBCTA versus CS alone could be observed.

Overview of isoprene monomer and polyisoprene production processes.

Isoprene monomer is employed in the manufacture of polyisoprene and various copolymers (with isobutylene, butadiene, styrene, other monomers). Recent surveys of air levels of isoprene in US monomer and polymer manufacturing facilities have demonstrated TWA concentrations <1 ppm in 90% of collected samples, and 98% were <10 ppm. Tumorigenic responses have been observed in isoprene-exposed rodents. However, the relevance of these findings to health in occupational environments can only be assessed following completion of additional and ongoing mechanistic research.

Human exposures to monomers resulting from consumer contact with polymers.

Many consumer products are composed completely, or in part, of polymeric materials. Direct or indirect human contact results in potential exposures to monomers as a result of migrations of trace amounts from the polymeric matrix into foods, into the skin or other bodily surfaces. Typically, residual monomer levels in these polymers are <100 p.p.m., and represent exposures well below those observable in traditional toxicity testing. These product applications thus require alternative methods for evaluating health risks relating to monomer exposures. A typical approach includes: (a) assessment of potential human contacts for specific polymer uses; (b) utilization of data from toxicity testing of pure monomers, e.g. cancer bioassay results; and (c) mathematical risk assessment methods. Exposure potentials are measured in one of two analytical procedures: (1) migration of monomer from polymer into a simulant solvent (e.g. alcohol, acidic water, vegetable oil) appropriate for the intended use of the product (e.g. beer cans, food jars, packaging adhesive, dairy hose); or (2) total monomer content of the polymer, providing worse-case values for migratable monomer. Application of toxicity data typically involves NOEL or benchmark values for non-cancer endpoints, or tumorigenicity potencies for monomers demonstrated to be carcinogens. Risk assessments provide exposure 'safety margin' ratios between levels that: (1) are projected to be safe according to toxicity information, and (2) are potential monomer exposures posed by the intended use of the consumer product. This paper includes an example of a health risk assessment for a chewing gum polymer for which exposures to trace levels of butadiene monomer occur.

[Angiography with multi-slice spiral CT. Detecting plaque, before it causes symptoms]. / Angiographie mit dem Mehrschicht-Spiral-CT. Plaques erkennen, bevor sie Beschwerden machen.

The short imaging time of 1/4 second, renders the new generation of multiple-slice spiral CT devices with ECG gating enables the investigation of the heart without disturbing motion artefacts. With this method, calcifications of the coronary arteries can be detected or excluded. Certain amounts of coronary "chalk" in asymptomatic patients with risk factors point to coronary artery disease and thus a need to modulate the risk factors. With the aid of intravenous injection of contrast medium during the examination, non-calcified plaques in the coronary arteries can also be visualized. A limiting factor is that the patient's heart rate should not exceed 60 beats per minute. Indications for this examination are visualization of coronary vessels with the aim of excluding coronary artery disease, pre-operative planning and monitoring of bypass vessels, and non-invasive follow-up after PTCA and stenting.

Laboratory-based surveillance for vancomycin-resistant enterococci: utility of screening stool specimens submitted for Clostridium difficile toxin assay.

OBJECTIVE: To study vancomycin-resistant enterococci (VRE) gastrointestinal colonization prevalence in high-risk hospitalized patients and to assess the cost and utility of this laboratory-based surveillance. SETTING: Large university teaching hospital. DESIGN: Quarterly prevalence culture survey of 50 stool specimens submitted for Clostridium difficile toxin A assay from October 1996 through June 1999 (n=526). Screening culture survey of all C difficile-positive stool specimens from July 1998 through June 1999 (n=140). PATIENTS: Specimens for analysis were collected from patients who were admitted to the hospital and who had C difficile toxin A testing ordered. Patient samples were excluded from analysis if they were obtained from patients not hospitalized at UCLA Medical Center, if the C difficile toxin assay result was indeterminate, or if the patient was known to have previous VRE colonization or infection. RESULTS: During quarterly surveillance, VRE was detected in 19.8%, C difficile toxin A in 9.5%, and both VRE and C difficile toxin A in 3.2% of stool specimens submitted for C difficile toxin assay. Patients whose stool specimens were positive for C difficile toxin A were significantly more likely than those whose specimens were negative to have VRE detected (odds ratio, 2.3; 95% confidence interval, 1.2-4.5). Based on these findings, in July 1998, we began routine screening of all C difficile-positive stool specimens for VRE. From July 1998 through June 1999, 58 (41.4%) of 140 patients with C difficile-positive specimens had VRE newly detected in the stool. The combined cost of the two laboratory-based surveillance strategies was approximately $62 per VRE-positive patient identified and $5,800 per year. CONCLUSION: Quarterly surveillance of stool submitted for C difficile assay combined with screening all C difficile-positive stools is a cost-effective and efficient strategy for detecting VRE stool colonization among high-risk hospitalized patients. Such a laboratory-based surveillance should be included as part of a comprehensive program to limit nosocomial VRE transmission.