Tag Archives: GSK503

Based on MALDI TOF MS identification of colonies displaying distinct

Based on MALDI-TOF MS identification of colonies displaying distinct colony appearance on Slanetz–Bartley agar, E. faecium (50%) was detected as the most prevalent enterococcal species, followed by E. faecalis (27%), E. hirae (16%) and E. avium (9%). AMP resistance was detected in E. faecium and E. faecalis isolated from 12% and 3% of the dogs, respectively. The faecal concentrations of AMPR enterococci varied from 8×101 to 2.1×103cfu/g for E. faecium (<1–100% of total E. faecium) and from 103 to 6×103cfu/g for E. faecalis (<1–1.7% of total E. faecalis). Each laboratory replicate alone had a sensitivity of 100% for identification of E. faecalis, AMPRE. faecalis and E. avium/raffinosus carriers. The same sensitivity was observed using one of the replicates for identification of E. coli, CTXRE. coli and E. hirae, whereas the other replicate would have missed between one and two carriers for each of these bacterial targets (Se=98%, 88% and 94%, respectively). Use of a single replicate for detection of the remaining bacterial targets (AMPRE. coli and total and AMPRE. faecium) would have missed between one and four carriers (Se=92–96%). Data analysis showed that total enterococci were less frequent amongst dogs with gastrointestinal problems (p=0.05, OR=0.07, 95% CI 0.003-0.7). A borderline significant association was found between carriage of AMPR enterococci and AMPRE. coli (p=0.07, OR=3.2, 95% CI=0.9–1.3).
Discussion
The resistance phenotypes investigated in this GSK503 study are of high clinical relevance in small animal veterinary practice in view of the importance of β-lactams for treatment of common infections in dogs such as urinary tract infections, which are often associated to E. coli and to a lesser extent to enterococci. Various studies have shown that recent treatment with β-lactams is a risk factor for carriage of resistant bacteria in dogs (Gibson et al., 2011; Lawrence et al., 2013). The results of this study indicate that dogs without a recent history of antimicrobial treatment shed resistant bacteria such as AMPRE. coli (40%), AMPRE. faecium (12%), CTXRE. coli (8%) and AMPRE. faecalis (3%) at different frequencies and concentrations. The prevalence of AMPRE. coli carriers (40%) in Danish dogs was two to four times higher than those reported by previous studies in other countries (Murphy et al., 2009; Wedley et al., 2011), whereas the prevalence of CTXRE. coli carriers (8%) fell within the range of expected carriage frequencies (1–18.5%) (Haenni et al., 2014; Murphy et al., 2009). However, comparison between different studies is difficult due to biases associated to geographical, temporal and methodological factors. In addition, dogs included from a University veterinary facility may bias the results toward a higher proportion of carriers. However, our study population represented both primary and secondary/tertiary cases with 57% of dogs being primary cases and 1/3 of the dogs being healthy individuals.
Quantitative microbiological risk assessment is advised to assess the role of animals as a source of antimicrobial resistance in humans (Snary, 2008). The median faecal load of AMPRE. coli (3.2×104cfu/g) in dog carriers was slightly higher to that of CTXRE. coli (8.6×103cfu/g). However, CTXRE. coli are resistant bacteria of higher impact on public health due to the importance of third generation cephalosporins in the therapy of severe E. coli infections in humans. Faecal shedding of these bacteria was extremely variable amongst dogs (8×101 to 2×105cfu/g) and even higher variability (1×102 to 6×1010cfu/g) was reported by a recent study in The Netherlands (Baede et al., 2015). The average faecal concentration of CTXRE. coli in Danish dogs was close to those found in weaners and finishers (105 and 103, respectively) but lower than the average in piglets (107) in Danish pig farms positive for ESBL-producing E. coli (Hansen et al., 2013).

GSK503 br Discussion br Our study determined the

Discussion

Our study determined the average excursion of the diaphragms during tidal breathing in a standing position in a health screening center cohort using dynamic chest radiography (“dynamic X-ray phrenicography”). These findings are important because they provide reference values of diaphragmatic motion during tidal breathing useful for the diagnosis of diseases related to respiratory kinetics. Our study also suggests that dynamic X-ray phrenicography is a useful method for the quantitative evaluation of diaphragmatic motion with a radiation dose comparable to conventional posteroanterior chest radiography (22).

Our study demonstrated that the average excursions of the bilateral GSK503 during tidal breathing (right: 11.0 mm, 95% CI 10.4 to 11.6 mm; left: 14.9 mm, 95% CI 14.2 to 15.5 mm) were numerically less than those during forced breathing in previous studies using other modalities 2; 7 ;  8. Using fluoroscopy, Alexander reported that the average right excursion was 27.5 mm and the average left excursion was 31.5 mm during forced breathing in the standing position in 127 patients (2). Using ultrasound, Harris et al. reported that the average right diaphragm excursion was 48 mm during forced breathing in the supine position in 53 healthy adults (7). Using MR fluoroscopy, Gierada et al. reported that the average right excursion was 44 mm and the average left excursion was 42 mm during forced breathing in the supine position in 10 healthy volunteers (8). The difference in diaphragmatic excursion during tidal breathing versus forced breathing is unsurprising.

Our study showed that the excursion and peak motion speed of the left diaphragm are significantly greater and faster than those of the right. With regard to the excursion, the results of our study are consistent with those of previous reports using fluoroscopy in a standing position 2 ;  3. However, in the previous studies evaluating diaphragmatic motion in the supine position, the asymmetric diaphragmatic motion was not mentioned 7 ;  8. The asymmetric excursion of the bilateral diaphragm may be more apparent in the standing position, but may not be detectable or may disappear in the supine position. Although we cannot explain the reason for the asymmetry in diaphragmatic motion, we speculate that the presence of the liver may limit the excursion of the right diaphragm. Regarding the motion speed, to the best of our knowledge this study is the first to evaluate it. The faster motion speed of the left diaphragm compared to that of the right diaphragm would be related to the greater excursion of the left diaphragm.

We found that higher BMI and higher tidal volume were independently associated with the increased excursions of the bilateral diaphragm by both univariate and multivariate analyses, although the strength of these associations was weak. We cannot explain the exact reason for the correlation between BMI and the excursion of the diaphragm. However, a previous study showed that BMI is associated with peak oxygen consumption (23), and the increased oxygen consumption in an obese participant may affect diaphragmatic movement. Another possible reason is that lower thoracic compliance due to higher BMI may cause increased movement of the diaphragm for compensation. Regarding the correlation between tidal volume and excursion of the diaphragm, given that diaphragmatic muscle serves as the most important respiratory muscle, the result is to be expected. Considering our results, the excursion evaluated by dynamic X-ray phrenicography could potentially predict tidal volume.

Our study has several limitations. First, we included only 172 volunteers, and additional studies on larger participant populations are required to confirm these preliminary findings. Second, we evaluated only the motion of the highest point of the diaphragms for the sake of simplicity, and three-dimensional motion of the diaphragm could not be completely reflected in our results. However, we believe that this simple method would be practical and more easily applicable in a clinical setting.

br Our study has several limitations First

Our study has several limitations. First, we included only 172 volunteers, and additional studies on larger participant populations are required to confirm these preliminary findings. Second, we evaluated only the motion of the highest point of the diaphragms for the sake of simplicity, and three-dimensional motion of the GSK503 could not be completely reflected in our results. However, we believe that this simple method would be practical and more easily applicable in a clinical setting.

Conclusions

The time-resolved quantitative analysis of the diaphragms with dynamic X-ray phrenicography is feasible. The average excursions of the diaphragms are 11.0 mm (right) and 14.9 mm (left) during tidal breathing in a standing position in our health screening center cohort. The diaphragmatic motion of the left is significantly larger and faster than that of the right. Higher tidal volume and BMI are associated with increased excursions of the bilateral diaphragm.

AcknowledgmentsThe authors acknowledge the valuable assistance of Hideo Ogata, MD, PhD, Norihisa Motohashi, MD, PhD, Misako Aoki, MD, Yuka Sasaki, MD, PhD, and Hajime Goto, MD, PhD, from the Department of Respiratory Medicine; Yuji Shiraishi, MD, PhD, from the Department of Respiratory Surgery; and Masamitsu Ito, MD, PhD, Atsuko Kurosaki, MD, Yoichi Akiyama, RT, Kenta Amamiya, RT, and Kozo Hanai, RT, PhD, from the Department of Radiology, Fukujuji Hospital, for their important suggestions. The authors also acknowledge the valuable assistance of Alba Cid, MS, for editorial work on the manuscript. Yoshitake Yamada, MD, PhD, is a recipient of a research fellowship from the Uehara Memorial Foundation.

Appendix. Supplementary DataThe following is the supplementary data to this article:
To view the video inline, enable JavaScript on your browser. However, you can download and view the video by clicking on the icon belowVideo S1.
 A representative video of sequential chest radiographs obtained by chest dynamic radiography for the motion of the diaphragms (“dynamic X-ray phrenicography”). A board-certified radiologist placed a point of interest (red point) on the highest point of each diaphragm on the radiograph at the resting end-expiratory position. These points were automatically traced by the template-matching technique throughout the respiratory phase. Based on locations of the points on sequential radiographs, the vertical excursions and the peak motion speeds of the bilateral diaphragm were calculated (Fig 2c).Help with MP4 filesOptionsDownload video (1042 K)
Data S1.
 Multivariate analysis of associations between the excursions and participant demographics using age, gender, BMI, tidal volume, VC, FEV1, and smoking history as factors (Model 2).Help with DOCX filesOptionsDownload file (23 K)

The bilateral diaphragm is the most important respiratory muscle. Diaphragmatic dysfunction is an underappreciated cause of respiratory difficulties and may be due to a wide variety of issues, including surgery, trauma, tumor, and infection (1). Several previous studies have evaluated diaphragmatic motion using fluoroscopy 2; 3; 4 ;  5, ultrasound 6 ;  7, magnetic resonance (MR) fluoroscopy (dynamic MR imaging [MRI]) 8; 9; 10; 11 ;  12, and computed tomography (CT) 13; 14; 15 ;  16. However, the data of the previous studies using ultrasound, MR fluoroscopy, or CT were obtained in a supine position 6; 7; 8; 9; 10; 11; 12; 13; 14; 15 ;  16, not in a standing position. Also, while the data of the previous studies using fluoroscopy were obtained in a standing position, the data were assessed under forced breathing 2 ;  3, not under tidal or resting breathing. Thus, diaphragmatic motion in a standing position during tidal breathing remains unclear, even though it is essential for understanding respiratory physiology in our daily life. Furthermore, the evaluation of diaphragmatic motion using fluoroscopy, ultrasound, dynamic MRI, or CT has not been used as a routine examination because of limitations, including high radiation dose, small field of view, low temporal resolution, and/or high cost.

br Discussion br Our study determined

Discussion

Our study determined the average excursion of the diaphragms during tidal breathing in a standing position in a health screening center cohort using dynamic chest radiography (“dynamic X-ray phrenicography”). These findings are important because they provide reference values of diaphragmatic motion during tidal breathing useful for the diagnosis of diseases related to respiratory kinetics. Our study also suggests that dynamic X-ray phrenicography is a useful method for the quantitative evaluation of diaphragmatic motion with a radiation dose comparable to conventional posteroanterior chest radiography (22).

Our study demonstrated that the average excursions of the bilateral GSK503 during tidal breathing (right: 11.0 mm, 95% CI 10.4 to 11.6 mm; left: 14.9 mm, 95% CI 14.2 to 15.5 mm) were numerically less than those during forced breathing in previous studies using other modalities 2; 7 ;  8. Using fluoroscopy, Alexander reported that the average right excursion was 27.5 mm and the average left excursion was 31.5 mm during forced breathing in the standing position in 127 patients (2). Using ultrasound, Harris et al. reported that the average right diaphragm excursion was 48 mm during forced breathing in the supine position in 53 healthy adults (7). Using MR fluoroscopy, Gierada et al. reported that the average right excursion was 44 mm and the average left excursion was 42 mm during forced breathing in the supine position in 10 healthy volunteers (8). The difference in diaphragmatic excursion during tidal breathing versus forced breathing is unsurprising.

Our study showed that the excursion and peak motion speed of the left diaphragm are significantly greater and faster than those of the right. With regard to the excursion, the results of our study are consistent with those of previous reports using fluoroscopy in a standing position 2 ;  3. However, in the previous studies evaluating diaphragmatic motion in the supine position, the asymmetric diaphragmatic motion was not mentioned 7 ;  8. The asymmetric excursion of the bilateral diaphragm may be more apparent in the standing position, but may not be detectable or may disappear in the supine position. Although we cannot explain the reason for the asymmetry in diaphragmatic motion, we speculate that the presence of the liver may limit the excursion of the right diaphragm. Regarding the motion speed, to the best of our knowledge this study is the first to evaluate it. The faster motion speed of the left diaphragm compared to that of the right diaphragm would be related to the greater excursion of the left diaphragm.

We found that higher GSK503 BMI and higher tidal volume were independently associated with the increased excursions of the bilateral diaphragm by both univariate and multivariate analyses, although the strength of these associations was weak. We cannot explain the exact reason for the correlation between BMI and the excursion of the diaphragm. However, a previous study showed that BMI is associated with peak oxygen consumption (23), and the increased oxygen consumption in an obese participant may affect diaphragmatic movement. Another possible reason is that lower thoracic compliance due to higher BMI may cause increased movement of the diaphragm for compensation. Regarding the correlation between tidal volume and excursion of the diaphragm, given that diaphragmatic muscle serves as the most important respiratory muscle, the result is to be expected. Considering our results, the excursion evaluated by dynamic X-ray phrenicography could potentially predict tidal volume.

Our study has several limitations. First, we included only 172 volunteers, and additional studies on larger participant populations are required to confirm these preliminary findings. Second, we evaluated only the motion of the highest point of the diaphragms for the sake of simplicity, and three-dimensional motion of the diaphragm could not be completely reflected in our results. However, we believe that this simple method would be practical and more easily applicable in a clinical setting.