Airway and systemic inflammatory responses to ultrafine carbon black particles and ozone in older healthy subjects

Increased adverse health effects in older subjects due to exposure to ambient air pollutants may be related to the inflammatory response induced by these contaminants. The aim of this study was to assess airway and systemic inflammatory responses in older healthy subjects to a controlled experimental exposure with spark-generated elemental carbon black ultrafine particles (cbUFPs) and ozone (O₃). Twenty healthy subjects, age 52–75 years, were exposed on three occasions separated by at least 8 weeks. The exposures to filtered air (FA), to cbUFP (50 μg/m³), or to cbUFP in combination with 250 ppb ozone (cbUFP + O₃) for 3 h with intermittent exercise were performed double blind, and in random order. Sputum and blood samples were collected 3.5 h after each exposure. Exposure to cbUFP + O₃ significantly increased plasma club cell protein 16 (CC16), the number of sputum cells, the number and percent of sputum neutrophils, and sputum interleukin 6 and matrix metalloproteinase 9. Exposure to cbUFP alone exerted no marked effect, except for an elevation in sputum neutrophils in a subgroup of 13 subjects that displayed less than 65% sputum neutrophils after FA exposure. None of the inflammatory markers was correlated with age, and serum cardiovascular risk markers were not markedly affected by cbUFP or cbUFP + O₃. Exposure to cbUFP+O₃ induced a significant airway and systemic inflammatory response in older healthy volunteer subjects. The effects induced by cbUFP alone suggest that the inflammation was predominantly mediated by O₃, although one cannot rule out that the interaction of cbUFP and O₃ played a role.     

The presence of positive surgical margins in patients with organ-confined prostate cancer results in biochemical recurrence at a similar rate to that in patients with extracapsular extension and PSA≤10 ng/ml

PurposesWe investigated whether patients with organ-confined prostate cancer (PCa) and positive surgical margins (SMs) had a similar biochemical recurrence (BCR) risk compared with patients with pT3a and preoperative prostate-specific antigen (PSA) levels≤10 ng/ml. Furthermore, we examined the effects of incorporating SM status, Gleason score (Gls), and preoperative PSA level into the discrimination accuracy of the current tumor node metastasis-staging system.Materials and methodsWe analyzed 863 PCa patients treated with radical prostatectomy from 1999 to 2008. Only individuals with pT2N0 or pT3N0, without neoadjuvant or adjuvant therapy, were included. We performed chi-square automatic interaction detection analysis to generate a classification model for predicting BCR by analyzing interactions between age at surgery, SM status, Gls, PSA, and tumor stage, tumor volume and relative tumor volume. Cox regression analyses tested the relationship between SM status and BCR rate after stratification according to T-stage and the novel classification. The predictive and discrimination accuracy of the current T-stage and of the classification model was quantified with time-dependent receiver operating characteristics and integrated discrimination improvement. The topographical association between extracapsular extension of PCa and positive SM was analyzed in patients with pT3aR1 using a computational reconstruction diagram of the prostate.ResultsThe chi-square automatic interaction detection analysis found interactions among pT Stage, SM status, PSA and Gls and generated a classification model for BCR prediction: pT2R0, pT2R1, pT3a PSA≤10 ng/ml, pT3a PSA>10 ng/ml and pT3b. Men with pT2R1 had a shorter time to BCR compared with men with pT3a-PSA≤10 ng/ml (P<0.0001). Gls≥7a was correlated with a poorer BCR rate than Gls≤7a in men with pT2R1 or pT3a PSA≤10 ng/ml (P = 0.012). The rank order (highest to lowest) for the risk of developing BCR was pT3b>pT2R1/pT3a-PSA>10 ng/ml>pT2R1/pT3a PSA≤10 ng/ml>pT2R0 (P<0.0001). Discrimination accuracy gains were observed when PCa was stratified according to the novel classification (P<0.0001). A topographical association between extracapsular extension and positive SM was found in patients with pT3aR1 (P = 0.01).ConclusionPatients with pT2R1 develop a similar BCR risk to that of patients with pT3a PSA≤10 ng/ml. Gls≥7b is associated with a high BCR risk in these patient groups. Including SM status, PSA, and Gls in pT stage appears to improve prognostic stratification in patients with PCa.     

Detection of iso‐α‐acids to confirm beer consumption in postmortem specimens

Iso‐α‐acids (IAAs) can be used as markers for the consumption of beer. Postmortem specimens from a range of coronial cases were analyzed for IAAs in order to determine the prevalence of beer consumption and any correlation to blood alcohol concentrations (BAC). A total of 130 cases were included in this study including those where beer was mentioned in the case circumstances, cases where beer was not mentioned specifically but alcohol was detected, and cases where neither beer was mentioned nor a positive BAC was present. Available blood, serum, vitreous humour and urine specimens were analyzed. Of the 50 cases where beer was mentioned, 86% had one or more IAAs detected. In cases that only had a positive BAC (n = 60), 57% of these cases also showed the presence of these beer markers. IAAs were detected in specimens obtained from traumatized, burnt, and decomposed cases with a mention of beer consumption or where BAC was positive in blood. No IAAs were detected in cases where BAC was negative. There was little or no correlation between blood IAA concentrations and BAC. This study demonstrates the possible detection of IAAs as a marker for beer consumption. Copyright © 2014 John Wiley & Sons, Ltd.     

Magnetresonanztomographische Diagnostik der peripheren Durchblutung*

PURPOSE: This article describes the potential of dynamic contrast- enhanced magnetic resonance tomography (DCE-MRT) for the visualization and quantification of blood flow of lower leg muscles at rest and after individually adjusted muscular exercise. PATIENTS AND METHODS: Five cases were chosen to exemplify the qualitative and semi-quantitative blood flow evaluation in the lower leg muscles. The crural muscle state was determined with an isometric maximal strength measurement from a female patient with peripheral arterial occlusive disease (pAVK), a male patient with coronary heart disease (KHK) without clinical signs of a pAVK, a volunteer with sufficient physical activity in accordance with the Freiburg Questionnaire of Physical Activity and two professional athletes. After calibration of the plantarflexion ergometer MR-PEDALO (Figures 2a and 2b) for the execution of auxotonic muscle work a 1- minute alternating foot extension and flexion exercise on MRPEDALO was performed in the MR machine. Instead of the lower leg splint shown in Figures 2a and 2b the MR coil fits exactly in MR-PEDALO used for DCE-MRT. Mechanical work performed during the 1-minute exercise ranged from 52 watt seconds (Ws) to 244 Ws (0.65 W to 4.07 W), indicating similar interindividual work loads in relation to the individual maximum isometric strength. DCE-MRT was performed at rest and immediately after auxotonic exercise test (T1w 2DFLASH- GE sequence with TR/TE/alpha: 100 ms/6 ms/70 degrees; field of view: 400; matrix: 81 x 256; slice thickness: 10 mm; acquisitions: 73 at 8.3 s each; total examination time: 9.24 min; bolus application of Magnevist, Schering, 0.02 ml/kg kg, 20 ml bolus NaCl, flow 2 ml/s, 22G cannula in a cubital vein). Signal intensity (SI) curves were analyzed with DynaVision (MeVis gGmbH, Bremen, Germany). RESULTS: Measuring peripheral blood flow needs appropriate muscular stress tests. The SI-curves of the region of interest (ROI) representing the peroneus, tibialis anterior and gastrocnemius muscle run almost parallel at rest. Workloads between 52 Ws and 244 Ws (0.65 W and 4.07 W), similar in relation to the individual maximum isometric strength, induce distinctive changes of the upslope, wash-in, peak and washout of SI-curves preferably for the peroneus muscle and less predominant also for the tibialis anterior muscle and gastrocnemius muscle respectively. The first case, a 55-year-old female patient with peripheral arterial occlusive disease (pAVK) stage Fontaine IIb before (Figure 3a) and after (Figure 3b) percutaneous transluminal angioplasty (PTA) of a right femoral artery stenosis shows after interventional treatment a rapid post-exercise SI-increase in the peroneus muscle. The steeper SI-curve indicates a better contrast medium inflow due to an improved perfusion. The second case, a 65-year-old man suffering from coronary heart disease without clinical signs of pAVK (Figure 4) exercised with a workload of 92 Ws. After stress test the ROI for the peroneus muscle shows a clear intensity increase. After exercise the SI-curve for the tibialis anterior muscle shows a similar, but less predominant change while the shape of the SI-curve of the gastrocnemius muscle remains mainly identical. A 23-year-old male person with average physical activity (Figure 5) performed DCE-MRT of the left lower leg after stress test with 172 Ws demonstrating a rapid signal increase in the peroneus muscle while the synergistic tibialis anterior muscle and antagonistic gastrocnemius muscle show a comparatively slow contrast-medium wash-in. A 26-year-old male athlete (Figure 6) exercised with 196 Ws showing a rapid contrast medium inflow in the peroneus muscle and initially also in the synergistic tibialis anterior muscle. A contrast-medium wash-out appears in both muscles, while the shape of the gastrocnemius muscle SI-curve remains substantially unchanged. A 26-year-old female athlete (Figure 7) exercised with 244 Ws. Post exercise SI-curves show a distinctive and rapid increase of contrast medium wash-in with a sharp peak particularly in the peroneus muscle and similarly in the tibialis anterior and gastrocnemius muscle. After exercise all SI-curves show a wash-out phase. CONCLUSION: SI-curves show relative increase in correlation with Time-to-Peak (TTP) decrease and Mean-Intensity to Time Ratio (MITR) increase indicating blood flow reserve mobilization after exercise. Individual muscle state seems to be linked to muscle recruitment and muscle coordination reflected by post-exercise SI-curves. The gastrocnemius muscle shows comparatively low SI-curve changes after muscular load test. Further methodological standardization and optimization of the stress test is mandatory to assure intra- and interindividual comparisons. Due to direct visualization and quantitative evaluation of the peripheral microcirculation DCE-MRT has a diagnostic potential for monitoring therapeutic response in peripheral circulation disorders and sports medicine.     

Reduced myocardial perfusion reserve and transmural perfusion gradient in heart transplant arteriopathy assessed by magnetic resonance imaging

OBJECTIVES: The goal of this study was to detect transplant arteriopathy (Tx-CHD) by a reduced myocardial perfusion reserve (MPR) and resting endomyocardial/epimyocardial perfusion ratio (Endo/Epi ratio). BACKGROUND: Transplant arteriopathy often lacks clinical symptoms and is the reason for frequent surveillance angiography in heart transplant (Tx) recipients. Magnetic resonance perfusion imaging (MRPI) allows noninvasive assessment of transmural and selective endomyocardial and epimyocardial perfusion. METHODS: Fifteen healthy volunteers (controls) and three groups (A, B, C) of Tx recipients were included. In controls and patients, MPR (hyperemic/resting perfusion) and Endo/Epi ratio were determined with MRPI after injection of gadolinium-diethylenetriamine pentaacetic acid at rest and during hyperemia (intravenous adenosine). Group A (n = 10) had no left ventricular (LV) hypertrophy and/or prior rejection, while patients in group B (n = 10) had at least one of these characteristics. Patients in group A and B had a normal coronary angiogram and a coronary flow reserve (CFR) of > or =2.5 (CFR = hyperemic/resting blood flow). Group C (n = 7) had Tx-CHD diagnosed by angiography and a reduced CFR (<2.5). RESULTS: In group C, MPR (1.7 +/- 0.5) and Endo/Epi ratio (1.1 +/- 0.2) were significantly reduced compared with controls (4.2 +/- 0.7 and 1.6 +/- 0.3; both p < 0.0001), group A (3.6 +/- 0.7 and 1.6 +/- 0.2; both p < 0.0001) and B (2.7 +/- 0.9, p < 0.01 and 1.4 +/- 0.1, p < 0.04). Transplant arteriopathy can be excluded by an MPR of >2.3 with sensitivity and specificity of 100% and 85%. If LV hypertrophy and prior rejection are excluded, Tx-CHD can be excluded by an Endo/Epi ratio of >1.3 with 100% and 80%. CONCLUSIONS: Magnetic resonance perfusion imaging detects Tx-CHD by a decreased MPR. After exclusion of LV hypertrophy and prior rejection, resting Endo/Epi ratio alone might be sufficient to indicate Tx-CHD.     

Early identification of peritonitis by peritoneal cytokine measurement

PURPOSE: The assessment of plasma cytokine levels adds a useful tool to the diagnostic measures in severe inflammatory diseases. Proinflammatory cytokine levels in abdominal fluid after abdominal surgery have been shown to far exceed plasma cytokine levels. Thus, we investigated the local release of interleukin 1, interleukin 6, and tumor necrosis factor- in patients after colorectal surgery during the early postoperative period to evaluate whether it may serve as an indicator of evolving peritonitis. METHOD: In a prospective, observational pilot study, the first 12 consecutive patients who did not develop any postoperative complications (Group I), and the first 12 patients with secondary peritonitis caused by an anastomotic leakage (Group II), were included in the study. Interleukin 6, interleukin 1, and tumor necrosis factor- levels were determined in the abdominal exudate and compared between the groups within the first four days after colorectal surgery. RESULTS: Abdominal fluid interleukin 6 levels in Group II patients were higher (162,500 ± 105,800 pg/ml) as early as the first postoperative day compared with Group I (27,940 ± 13,860 pg/ml; P < 0.0001); this lasted for the whole observation period. The same applies to tumor necrosis factor- levels (461.4 ± 167.8 pg/ml vs. 175.8 ± 178.6 pg/ml on day 1; P = 0.0007). The difference in interleukin 1 cytokine levels became statistically significant on the third postoperative day. Moreover, abdominal fluid cytokine levels rose in Group II, whereas they remained virtually unchanged or even tended to decrease over time in Group I. CONCLUSION: We suggest that the estimation of the peritoneal cytokine levels might be an additional diagnostic tool that can support the early recognition of peritonitic complications in colorectal surgery.