Monthly Archives: June 2017

br Our study demonstrated that the average excursions of

Our study demonstrated that the average excursions of the bilateral purchase Atractyloside Dipotassium Salt 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.

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.

Multiple linear regression analysis using all variables

Multiple linear regression analysis using all variables as factors (Model 1) demonstrated that weight, BMI, and tidal volume were independently associated with the bilateral excursion of the diaphragms (all P < 0.05) after adjusting for other clinical variables, including age, gender, smoking history, height, VC, %VC, FEV1, FEV1%, and %FEV1. There were no significant associations between the excursion of the diaphragms and variables including age, gender, smoking history, height, VC, %VC, FEV1, FEV1%, and %FEV1 (Table 4). Additionally, a multiple linear regression model using age, gender, BMI, tidal volume, VC, FEV1, and smoking history as factors (Model 2) was also fit as a sensitivity analysis, taking into account the correlation among variables (eg, BMI, height, and weight; VC and %VC; FEV1, FEV1%, and %FEV1). Model 2 (Supplementary Data S1) gave results consistent with Model 1 (Table 4): higher BMI and higher tidal volume were independently associated with the increased bilateral excursion of the diaphragms (all P < 0.05). The adjusted R2 in Model 1 was numerically higher than that in Model 2 (right, 0.19 vs. 0.16, respectively; left, 0.16 vs. 0.13, respectively).

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 order KY 02111 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.

br Our study demonstrated that the average

Our study demonstrated that the average excursions of the bilateral pdgfr 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.

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.

br The purpose of this

The purpose of this study was to evaluate diaphragmatic motion during tidal breathing in a standing position in a health screening center cohort using dynamic chest radiography in association with participants\’ demographic characteristics.

Materials and Methods

Study Population

This cross-sectional study was approved by the institutional review board, and all the participants provided written informed consent. From May 2013 to February 2014, consecutive 220 individuals who visited the health screening of our hospital and met the following inclusion criteria for the study were recruited: age greater than 20 years, scheduled for conventional chest radiography, and underwent pulmonary function test. Patients with any of the following criteria were excluded: pregnant (n  =  0), potentially pregnant or lactating (n  =  0), refused to provide informed consent (n  =  22), had incomplete datasets of dynamic chest radiography (n  =  3), had incomplete datasets of pulmonary function tests (n  =  1), could not follow tidal breathing instructions (eg, holding breath or taking a deep breath) (n  =  18), or their diaphragmatic motion could not be analyzed by the software described next (n  =  4). Thus, a total of 172 participants (103 men, 69 women; mean age 56.3 ± 9.8 years; age range 36–85 years) were finally included in the analysis ( Fig 1). The data from 47 participants of this study Tivozanib were analyzed in a different study (under review). The heights and weights of the participants were measured, and the body mass index (BMI, weight in kilograms divided by height squared in meters) was calculated.

Figure 1. Flow diagram of the study population.Figure optionsDownload full-size imageDownload high-quality image (83 K)Download as PowerPoint slide

Imaging Protocol of Dynamic Chest Radiology (“Dynamic X-Ray Phrenicography”)

Posteroanterior dynamic chest radiography (“dynamic X-ray phrenicography”) was performed using a prototype system (Konica Minolta, Inc., Tokyo, Japan) composed of an FPD (PaxScan 4030CB, Varian Medical Systems, Inc., Salt Lake City, UT, USA) and a pulsed X-ray generator (DHF-155HII with Cineradiography option, Hitachi Medical Corporation, Tokyo, Japan). All participants were scanned in the standing position and instructed to breathe normally in a relaxed way without deep inspiration or expiration (tidal breathing). The exposure conditions were as follows: tube voltage, 100 kV; tube current, 50 mA; pulse duration of pulsed X-ray, 1.6 ms; source-to-image distance, 2 m; additional filter, 0.5 mm Al + 0.1 mm Cu. The additional filter was used to filter out soft X-rays. The exposure time was approximately 10–15 seconds. The pixel size was 388 × 388 µm, the matrix size was 1024  × 768, and the overall image area was 40 × 30 cm. The gray-level range of the images was 16,384 (14 bits), and the signal intensity was proportional to the incident exposure of the X-ray detector. The dynamic image data, captured at 15 frames/s, were synchronized with the pulsed X-ray. The pulsed X-ray prevented excessive radiation exposure to the subjects. The entrance surface dose was approximately 0.3–0.5 mGy.

Image Analysis

The diaphragmatic motions on sequential chest radiographs (dynamic image data) during tidal breathing were analyzed using prototype software (Konica Minolta, Inc.) installed in an independent workstation (Operating system: Windows 7 Pro SP1; Microsoft, Redmond WA; CPU: Intel Core i5-5200U, 2.20 GHz; memory 16 GB). The edges of the diaphragms on each dynamic chest radiograph were automatically determined by means of edge detection using a Prewitt Filter 18 ;  19. A board-certified radiologist with 14 years of experience in interpreting chest radiography selected the highest point of each diaphragm as the point of interest on the radiograph of the resting end-expiratory position (Fig 2a). These points were automatically traced by the template-matching technique throughout the respiratory phase (Fig 2b, Supplementary Video S1), and the vertical excursions of the bilateral diaphragm were calculated (Fig 2c): the null point was set at the end of the expiratory phase, that is, the lowest point (0 mm) of the excursion on the graph is the highest point of each diaphragm at the resting end-expiratory position. Then the peak motion speed of each diaphragm was calculated during inspiration and expiration by the differential method (Fig 2c). If several respiratory cycles were involved in the 10 to 15-second examination time, the averages of the measurements were calculated.

br Our study demonstrated that the

Our study demonstrated that the average excursions of the bilateral diprenorphine 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.

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.

rock inhibitor br Part A br Data collection commenced after endotracheal

Part A

Data collection commenced after endotracheal intubation and connection of the endotracheal tube to the Humphrey ADE breathing system (time 0). The FGF was maintained at 150 mL kg−1 minute−1 for the first ten minutes of anaesthesia. Data were recorded every minute for the first five minutes and then at ten minutes. After ten minutes, the FGF was adjusted to 100 mL kg−1 minute−1. Data were recorded at 11 minutes. The body temperature and Pe’CO2 were also recorded.

The FGF was then reduced by 50–100 mL minute−1 in a step-wise manner with a minimum of five minutes between each reduction; until rebreathing occurred (defined as Pi′CO2 >5 mmHg (0.7 kPa)). Any transient increases in Pi′CO2 during periods of light anaesthesia or abnormal breathing patterns were ignored for the purposes of this study. Data were recorded one minute after each change in oxygen flow rate was made, to allow for stabilisation of depth of anaesthesia and respiratory parameters, and when rebreathing first occurred. Once rebreathing occurred, the FGF was then increased to the recommended 100 mL kg−1 minute−1 and Pi′CO2 and Pe’CO2 were observed to ensure they rock inhibitor returned to within normal limits.

Part B

In a sub group of animals, after the minimum FGF (χ mL minute−1) that just maintained a Pi′CO2 of 0 mmHg on the Humphrey ADE was established (point H), the animals were disconnected from the Humphrey ADE and anaesthesia was then maintained using a Bain non-rebreathing system. The animals were allowed to breathe spontaneously for 30–60 seconds until Pi′CO2 and Pe’CO2 readings were consistent, before data were recorded. If rebreathing (Pi′CO2 >5 mmHg (0.7 kPa)) occurred the oxygen flow rate was increased to 300 mL kg−1 minute−1, a rate that exceeded minute ventilation, for the remainder of the anaesthetic.

Statistical analysis

All statistical analysis was performed using the statistics program Minitab 16® (Minitab Inc.; PA, USA).

Descriptive analysis was performed on age, weight, FGF (mL kg−1 minute−1 and mL minute−1), Pi′CO2, Pe’CO2, fR and time into anaesthesia at which rebreathing occurred.

For Part A, a one-sample t test was used to obtain the 95% and 99% confidence interval (CI) for the Pi′CO2 and FGF (mL kg−1 minute−1) at which rebreathing occurred. A paired t test was used to assess the significance of sex, species and ASA score on the FGF at which rebreathing occurred. A one-way ANOVA test was used to assess the significance of the BCS.

For Part B, a one-sample t test was used to obtain the 95% CI of the FGF (mL kg−1 minute−1) and the Pi′CO2 at point H. A paired t-test was used to determine the significance of the difference in Pi′CO2, Pe’CO2 and fR at point H between the two breathing systems.

Results

Part A

Results are summarised in Table 1, Table 2 ;  Table 3. A total of 25 animals (13 cats, 12 dogs) were included in the study. Animals underwent a variety of diagnostic and elective surgical procedures (five castrations, four ovariohysterectomies, four dentals, three orthopaedic surgeries, six soft tissue surgeries, two endoscopies and one CSF tap). There were 10 males and 15 females. The mean ± standard deviation (SD) age was 4.7 ± 5 years (range 0.33–16), and body weight was 5.64 ± 3.26 kg (range 1.3–13.3). The median BCS (1–5) was 3 (range 2–4). Anaesthesia via the Humphrey ADE was maintained in all animals for the duration of the anaesthetic without significant side effects (hypoxaemia, hypotension, significant hypercapnoea: Pe’CO2 >60 mmHg (8 kPa)), and all animals recovered from anaesthesia uneventfully.

At the FGF of 100 mL kg−1 minute −1 (ie that recommended by the manufacturer of the ADE) rebreathing occurred in only one animal. This animal weighed 2.3 kg and so the total FGF was 230 mL minute−1. This total FGF was less than the minimum manufacturer\’s recommended total FGF (300 mL minute−1).

Exendin-3 (9-39) amide br Experiment noxious tail stimulation in

Experiment 2: noxious tail stimulation in an open arena

The effects of gender and habituation to the experimental procedure on nociceptive responses were investigated in a 2 × 2 factorial design. The effect of habituation was examined comparing responses of pigs that Exendin-3 (9-39) amide were either naïve or habituated to the experimental procedure. The 24 experimental pigs were distributed in six pens, each comprising a total of 12 pigs. Every home pen included the four experimental animals together with four companion animals selected out of the eight non-experimental pen mates. The companion pigs accompanied the experimental pigs throughout the procedures. Each pen was assigned to a specific treatment group at random.

Experimental set-up

Experiment 1: noxious stimulation at the pelvic limbs while confined in a cage

The tests of nociceptive thresholds occurred in an adjacent room (3.5 × 3.5 m) located approximately 5 m from the home pen. The room contained two identical test cages, each consisting of a spring scale for weighing pigs (Dan-Transducer, Gilleleje, Denmark) measuring 135 × 40 cm, and hinged at both ends in order to facilitate the passage of pigs. The two cages were placed parallel to each other, at a distance of 15 cm, in the centre of the room. During and between testing sessions, the room contained no other pigs.

Experiment 2: noxious tail stimulation in an open arena

The tests of nociceptive threshold occurred with the animals inside a 3 × 3 m arena placed in a 5.6 × 4.7 m room located approximately 30 m from the home pens. The arena was made of 1.2-m high plywood boards providing a barren environment in which approximately 500 g of straw was supplied together with a piece of rope attached to one of the sides. The boards of the arena impeded visual cues to the pigs. During and between testing sessions, the room contained no other pigs.

Nociceptive equipment

In both experiments, mechanical nociceptive thresholds were quantified with an electronic von Frey anesthesiometer (IITC Life Science Inc., CA, USA). The probe of the device had a rigid plastic tip [calibrated by the manufacturer for up to 1000 g force (gf)]. The tip was hollow with an outer diameter of 0.8 mm and an inner diameter of 0.5 mm. The stimulation surface was ring shaped with an area of approximately 0.3 mm2. The mechanical nociceptive threshold was recorded in gf with a cut-off value of 1000 gf. Within both experiment 1 and 2, the same operator applied the mechanical stimuli. Each operator had been trained on non-experimental animals to provide a stable and ramped rate of application. For each stimulus, the tip of the anesthesiometer was pressed perpendicular to the skin, and the angle of application was maintained constant to avoid fluctuations in the rate of application. The mechanical nociceptive stimuli were terminated by the occurrence of a behavioural response or when the cut-off value was reached. Any responses elicited by the initial contact of the tip with the skin in the absence of an applied pressure were ignored, and the stimulation was continued.

Habituation

Experiment 1: noxious stimulation at the pelvic limbs while confined in a cage

One week before nociceptive data collection, an investigator (dressed as the usual caretakers) entered the centre of the home pen of the pigs, stood still and stroked each pig on the back whenever approached. The session lasted until at least 75% of the pigs had been in physical contact with the experimenter. During the last 3 days before initiation of nociceptive testing, the pigs allocated to the ‘habituation’ treatment (comprising both groups due to be tested in isolation or with a companion animal) were habituated to the experimental set-up twice daily between 09.00 and 12.00 hours. For every habituation session, each experimental pig belonging to the ‘isolation’ treatment was habituated without the presence of a companion pen mate whereas the pigs assigned to the ‘social interaction’ treatment were accompanied by the same companion pen mate. During the initial habituation session, the two pigs entered the test room, passed through the test cages, and returned immediately to the home pen. During the following sessions, the pigs were locked inside the cages. The duration of the stay in the cages was increased gradually (1 minute added to each session) until the animals would accept confinement for a period of 5 minutes (i.e. no signs of distress or escape attempts). Whenever any escape attempt was observed (i.e. forceful behaviour involving attempts to rear on the pelvic limbs or turn around) the pigs were released from the cages. Following release from the cages, the pigs were returned to the home pen. The following measures were registered for each experimental pig: (i) time elapsed between the investigator entering the home pen and the pig leaving the home pen (seconds); (ii) degree of willingness to enter the test cage (0 = unwilling, 1 = reluctant, 2 = hesitant, 3 = willing and 4 = very willing) (session 2–5); and (iii) time elapsed between entrance to the test cage and release (seconds). All handling and recording was done by trained investigators. During nociceptive threshold testing, the investigators were blind to the habituation treatment, but blinding of the social isolation treatment was not possible.

br In human anaesthesia the

In human anaesthesia, the use of midazolam as a co-induction agent with propofol is well documented but the results in studies have been conflicting. Oxorn et al. (1997) did not observe any significant effect of midazolam on the propofol requirement whereas others have demonstrated an approximate 50% reduction in propofol dose for induction of anaesthesia if midazolam is given up to 10 minutes prior to propofol administration (Short & Chui 1991; Ong et al. 2000). Premedication with midazolam also increased the number of human patients achieving successful induction of general anaesthesia with a fixed low target of PTCI witho###http://www.APROTININ.NET/image/1-s2.0-S2211558714000508-gr3.jpg####ut major cardiovascular effects (Tzabar et al. 1996). In dogs, however, midazolam administered as an intramuscular (IM) premedication or intravenous (IV) co-induction agent, at doses of 0.1 and 0.2 mg kg−1 respectively, resulted in excitement and only a mild reduction in propofol requirement for induction of anaesthesia (Stegmann & Bester 2001; Covey-Crump & Murison 2008; Hopkins et al. 2014). These outcomes can be improved if midazolam is administered soon after a sub-hypnotic nisoldipine of propofol (Sanchez et al. 2013). Currently, there are no published reports of the effects of midazolam on either the plasma propofol target required or its cardiovascular and respiratory effects when used as a co-induction agent with PTCI in dogs.

In man, co-induction with lidocaine results in a lower dose requirement of propofol for induction of anaesthesia thus limiting the associated cardiovascular depression (Senturk et al. 2002; Kelsaka et al. 2011; Yang et al. 2013). In contrast, in dogs, there does not appear to be a sparing effect when lidocaine is administered immediately prior to propofol induction of anaesthesia (Braun et al. 2007). The effects of co-induction with lidocaine on PTCI in dogs, however, have not been investigated.

The aims of the present study were to evaluate if co-induction with midazolam or lidocaine could reduce the requirement of PTCI in healthy dogs for induction of general anaesthesia, and to investigate the effects of each drug combination on cardio-respiratory variables.

Materials and methods

The present clinical study was approved by the Ethics Committee of the School of Veterinary Medicine, University of Glasgow. The Veterinary Medicines Directorate approved the use of morphine, lidocaine and midazolam. Informed client consent was not obtained because the present study was started prior to becoming a requirement for publication.

Animals

Sixty client-owned dogs of various breeds, scheduled for elective surgical procedures at the Small Animal Hospital, University of Glasgow, were enrolled in the study.

The dogs were considered eligible for inclusion if categorized as American Society of Anesthesiologists (ASA) physical status I or II, based on history and physical examination. Haematology and serum biochemistry were carried out in some but not all dogs depending on the preference of the individual clinician referring the dog for anaesthesia. Dogs were not considered eligible if brachycephalic, significantly overweight, younger than 6 months or older than 8 years of age, receiving opioid analgesic medication or with a history of vomiting/regurgitation or respiratory obstruction.

Study protocol

For the purpose of the study, dogs were randomly assigned to one of three groups prior to premedication (n = 20 for each group) using a computer-generated random numbers list: saline group (SG), lidocaine group (LG) and midazolam group (MG). Dogs in SG received a total volume of 5 mL of 0.9% sodium chloride (Vetivex; Dechra Veterinary Products, UK) IV. Dogs in LG received 2 mg kg−1 of lidocaine 2% (Lidocaine hydrochloride injection 2%; Hameln Pharmaceuticals Ltd, UK) IV whereas those in MG received 0.2 mg kg−1 of midazolam (Hypnovel, 10 mg 2 mL−1; Roche Products Ltd, UK) IV. In the last two groups, the co-induction drug was diluted to a total volume of 5 mL with 0.9% sodium chloride to facilitate blinding.

br Medications used as part

Medications used as part of ERT (laronidase, idursulfase, or galsulfase, premedications and medications used in the treatment of infusion adverse reactions) and those not directly related to MPS management (such as oral contraceptives) were not tallied. For the purposes of this study, the number of medications used was defined as the number of different active pharmaceutical ingredients used during the study period; for example, if a patient received two courses of plain amoxicillin and one course of amoxicillin/clavulanate, these would be tallied as “two medications used during the study period.”

Tests were tallied as a single instance when performed on the same day; for example, complete blood cell count alone or complete blood cell count plus platelet count were both counted as a single test for statistical purposes as long as both tests were performed at a single visit. This practice was used for hematology and XAV-939 tests alike, including urea, creatinine, bilirubin, Alanine transaminase (ALT), aspartate transaminase (AST), Gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), alkaline phosphatase, cholesterol, glucose, sodium, potassium, chloride, magnesium, calcium, phosphorus, albumin, globulins, and total protein. Conversely, imaging tests of different body segments were counted separately even when performed on the same day.

Variables (medians) were initially assessed with regard to disease duration (equivalent to the age of the patient; in this analysis, data only from patients in the non-ERT group were taken into account) and presence/absence of cognitive involvement. To assess the influence of time on ERT on the variables of interest, data from the ERT group were included.

Statistical Analysis

Databases were constructed in Microsoft Office Excel 2010, and statistical analyses were performed in the SPSS 20.0 software environment. Descriptive data were described as frequencies, means and SDs, and medians and quartiles.

For evaluating the effect of the duration of disease on the frequency of medical intervention, a Pearson correlation was performed. The influence of the presence of cognitive involvement on other variables was then assessed using the Kruskal-Wallis test. The Mann-Whitney U test was used for comparison of the median number of medications, medical appointments, hospital admissions, tests, and surgical procedures in the ERT and non-ERT groups. To assess the influence of time on ERT on the variables of interest, data from the ERT group were included and Pearson correlation coefficients were calculated.

For all analyses, P values of less than 0.05 were considered statistically significant.

All monetary values ​​that are expressed in pounds sterling were obtained through the exchange rate provided by the Central Bank of Brazil (Banco Central do Brasil) on July 15, 2014. Because the data collected are prior to 2010, the monetary values determined may have suffered variations because of annual inflation rates in Brazil (around 6%).

Results

Forty-three patients with MPSs (I = 15, II = 23, VI = 5) were alive and registered at the four participating centers in 2010. Of these, only 35 met the inclusion criteria because 8 did not have any appointments in 2010 (e.g., Replacement sites were not regularly seen at the center). The medical records of one patient were not available for review. Therefore, the sample comprised 34 patients: 27 on ERT (“ERT group”) and 7 receiving supportive care only (“non-ERT group”). The reasons why patients from the non-ERT group were not receiving ERT were not clearly stated in medical records. Table 1 describes the profile of the patients included in the sample.

Appraisal of the Data Collection Instrument

Table 2 lists the variables associated with the cost of MPS treatment and describes our appraisal of the adequacy of record-keeping of these variables in patient charts.

br Recently dynamic chest radiography using a flat panel

Recently, dynamic chest radiography using a flat panel detector (FPD) system with a large field of view was introduced for clinical use. This technique can provide sequential chest radiographs with high temporal resolution during respiration (17), and the butein dose is much lower than that of CT. Also, whereas CT and MRI are performed in the supine or prone position, dynamic chest radiology can be performed in a standing or sitting position, which is physiologically relevant. To the best of our knowledge, no detailed study has analyzed diaphragmatic motion during tidal breathing by using dynamic chest radiography.

The purpose of this study was to evaluate diaphragmatic motion during tidal breathing in a standing position in a health screening center cohort using dynamic chest radiography in association with participants\’ demographic characteristics.

Materials and Methods

Study Population

This cross-sectional study was approved by the institutional review board, and all the participants provided written informed consent. From May 2013 to February 2014, consecutive 220 individuals who visited the health screening of our hospital and met the following inclusion criteria for the study were recruited: age greater than 20 years, scheduled for conventional chest radiography, and underwent pulmonary function test. Patients with any of the following criteria were excluded: pregnant (n  =  0), potentially pregnant or lactating (n  =  0), refused to provide informed consent (n  =  22), had incomplete datasets of dynamic chest radiography (n  =  3), had incomplete datasets of pulmonary function tests (n  =  1), could not follow tidal breathing instructions (eg, holding breath or taking a deep breath) (n  =  18), or their diaphragmatic motion could not be analyzed by the software described next (n  =  4). Thus, a total of 172 participants (103 men, 69 women; mean age 56.3 ± 9.8 years; age range 36–85 years) were finally included in the analysis ( Fig 1). The data from 47 participants of this study population were analyzed in a different study (under review). The heights and weights of the participants were measured, and the body mass index (BMI, weight in kilograms divided by height squared in meters) was calculated.

Figure 1. Flow diagram of the study population.Figure optionsDownload full-size imageDownload high-quality image (83 K)Download as PowerPoint slide

Imaging Protocol of Dynamic Chest Radiology (“Dynamic X-Ray Phrenicography”)

Posteroanterior dynamic chest radiography (“dynamic X-ray phrenicography”) was performed using a prototype system (Konica Minolta, Inc., Tokyo, Japan) composed of an FPD (PaxScan 4030CB, Varian Medical Systems, Inc., Salt Lake City, UT, USA) and a pulsed X-ray generator (DHF-155HII with Cineradiography option, Hitachi Medical Corporation, Tokyo, Japan). All participants were scanned in the standing position and instructed to breathe normally in a relaxed way without deep inspiration or expiration (tidal breathing). The exposure conditions were as follows: tube voltage, 100 kV; tube current, 50 mA; pulse duration of pulsed X-ray, 1.6 ms; source-to-image distance, 2 m; additional filter, 0.5 mm Al + 0.1 mm Cu. The additional filter was used to filter out soft X-rays. The exposure time was approximately 10–15 seconds. The pixel size was 388 × 388 µm, the matrix size was 1024  × 768, and the overall image area was 40 × 30 cm. The gray-level range of the images was 16,384 (14 bits), and the signal intensity was proportional to the incident exposure of the X-ray detector. The dynamic image data, captured at 15 frames/s, were synchronized with the pulsed X-ray. The pulsed X-ray prevented excessive radiation exposure to the subjects. The entrance surface dose was approximately 0.3–0.5 mGy.