High-Speed Video-Oculography for Measuring Three-Dimensional Rotation Vectors of Eye Movements in Mice

Background

The mouse is the most commonly used animal model in biomedical research because of recent advances in molecular genetic techniques. Studies related to eye movement in mice are common in fields such as ophthalmology relating to vision, neuro-otology relating to the vestibulo-ocular reflex (VOR), neurology relating to the cerebellum’s role in movement, and psychology relating to attention. Recording eye movements in mice, however, is technically difficult.

Methods

We developed a new algorithm for analyzing the three-dimensional (3D) rotation vector of eye movement in mice using high-speed video-oculography (VOG). The algorithm made it possible to analyze the gain and phase of VOR using the eye’s angular velocity around the axis of eye rotation.

Results

When mice were rotated at 0.5 Hz and 2.5 Hz around the earth’s vertical axis with their heads in a 30° nose-down position, the vertical components of their left eye movements were in phase with the horizontal components. The VOR gain was 0.42 at 0.5 Hz and 0.74 at 2.5 Hz, and the phase lead of the eye movement against the turntable was 16.1° at 0.5 Hz and 4.88° at 2.5 Hz.

Conclusions

To the best of our knowledge, this is the first report of this algorithm being used to calculate a 3D rotation vector of eye movement in mice using high-speed VOG. We developed a technique for analyzing the 3D rotation vector of eye movements in mice with a high-speed infrared CCD camera. We concluded that the technique is suitable for analyzing eye movements in mice. We also include a C++ source code that can calculate the 3D rotation vectors of the eye position from two-dimensional coordinates of the pupil and the iris freckle in the image to this article.     

Covert Anti-Compensatory Quick Eye Movements during Head Impulses

Background

Catch-up saccades during passive head movements, which compensate for a deficient vestibulo-ocular reflex (VOR), are a well-known phenomenon. These quick eye movements are directed toward the target in the opposite direction of the head movement. Recently, quick eye movements in the direction of the head movement (covert anti-compensatory quick eye movements, CAQEM) were observed in older individuals. Here, we characterize these quick eye movements, their pathophysiology, and clinical relevance during head impulse testing (HIT).

Methods

Video head impulse test data from 266 patients of a tertiary vertigo center were retrospectively analyzed. Forty-three of these patients had been diagnosed with vestibular migraine, and 35 with Menière’s disease.

Results

CAQEM occurred in 38% of the patients. The mean CAQEM occurrence rate (per HIT trial) was 11±10% (mean±SD). Latency was 83±30 ms. CAQEM followed the saccade main sequence characteristics and were compensated by catch-up saccades in the opposite direction. Compensatory saccades did not lead to more false pathological clinical head impulse test assessments (specificity with CAQEM: 87%, and without: 85%). CAQEM on one side were associated with a lower VOR gain on the contralateral side (p<0.004) and helped distinguish Menière’s disease from vestibular migraine (p = 0.01).

Conclusion

CAQEM are a common phenomenon, most likely caused by a saccadic/quick phase mechanism due to gain asymmetries. They could help differentiate two of the most common causes of recurrent vertigo: vestibular migraine and Menière’s disease.     

The Effect of Vestibulo-Ocular Reflex Deficits and Covert Saccades on Dynamic Vision in Opioid-Induced Vestibular Dysfunction

Patients with bilateral vestibular dysfunction cannot fully compensate passive head rotations with eye movements, and experience disturbing oscillopsia. To compensate for the deficient vestibulo-ocular reflex (VOR), they have to rely on re-fixation saccades. Some can trigger “covert” saccades while the head still moves; others only initiate saccades afterwards. Due to their shorter latency, it has been hypothesized that covert saccades are particularly beneficial to improve dynamic visual acuity, reducing oscillopsia. Here, we investigate the combined effect of covert saccades and the VOR on clear vision, using the Head Impulse Testing Device – Functional Test (HITD-FT), which quantifies reading ability during passive high-acceleration head movements. To reversibly decrease VOR function, fourteen healthy men (median age 26 years, range 21–31) were continuously administrated the opioid remifentanil intravenously (0.15 µg/kg/min). VOR gain was assessed with the video head-impulse test, functional performance (i.e. reading) with the HITD-FT. Before opioid application, VOR and dynamic reading were intact (head-impulse gain: 0.87±0.08, mean±SD; HITD-FT rate of correct answers: 90±9%). Remifentanil induced impairment in dynamic reading (HITD-FT 26±15%) in 12/14 subjects, with transient bilateral vestibular dysfunction (head-impulse gain 0.63±0.19). HITD-FT score correlated with head-impulse gain (R = 0.63, p = 0.03) and with gain difference (before/with remifentanil, R = −0.64, p = 0.02). One subject had a non-pathological head-impulse gain (0.82±0.03) and a high HITD-FT score (92%). One subject triggered covert saccades in 60% of the head movements and could read during passive head movements (HITD-FT 93%) despite a pathological head-impulse gain (0.59±0.03) whereas none of the 12 subjects without covert saccades reached such high performance. In summary, early catch-up saccades may improve dynamic visual function. HITD-FT is an appropriate method to assess the combined gaze stabilization effect of both VOR and covert saccades (overall dynamic vision), e.g., to document performance and progress during vestibular rehabilitation.     

A Method of Three-Dimensional Recording of Mandibular Movement Based on Two-Dimensional Image Feature Extraction

Background and Objective

To develop a real-time recording system based on computer binocular vision and two-dimensional image feature extraction to accurately record mandibular movement in three dimensions.

Methods

A computer-based binocular vision device with two digital cameras was used in conjunction with a fixed head retention bracket to track occlusal movement. Software was developed for extracting target spatial coordinates in real time based on two-dimensional image feature recognition. A plaster model of a subject’s upper and lower dentition were made using conventional methods. A mandibular occlusal splint was made on the plaster model, and then the occlusal surface was removed. Temporal denture base resin was used to make a 3-cm handle extending outside the mouth connecting the anterior labial surface of the occlusal splint with a detection target with intersecting lines designed for spatial coordinate extraction. The subject''s head was firmly fixed in place, and the occlusal splint was fully seated on the mandibular dentition. The subject was then asked to make various mouth movements while the mandibular movement target locus point set was recorded. Comparisons between the coordinate values and the actual values of the 30 intersections on the detection target were then analyzed using paired t-tests.

Results

The three-dimensional trajectory curve shapes of the mandibular movements were consistent with the respective subject movements. Mean XYZ coordinate values and paired t-test results were as follows: X axis: -0.0037 ± 0.02953, P = 0.502; Y axis: 0.0037 ± 0.05242, P = 0.704; and Z axis: 0.0007 ± 0.06040, P = 0.952. The t-test result showed that the coordinate values of the 30 cross points were considered statistically no significant. (P<0.05)

Conclusions

Use of a real-time recording system of three-dimensional mandibular movement based on computer binocular vision and two-dimensional image feature recognition technology produced a recording accuracy of approximately ± 0.1 mm, and is therefore suitable for clinical application. Certainly, further research is necessary to confirm the clinical applications of the method.     

A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content,Cardiovascular Risk Factors and Basal Metabolic Rate

Background

Fruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern.

Objectives

To study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans.

Methods

Thirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers.

Results

Weight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15±1.61 kg/m² to 22.30±1.7 kg/m², p = 0.24 nuts: from 22.54±2.26 kg/m² to 22.73±2.28 kg/m², p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519±721 kcal/day to 2763±595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1±6.0 gram/day to 25.6±9.6 gram/day, p<0.0001, nuts: from 12.4±5.7 gram/day to 6.5±5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistical significant only in the fruit group (from 7.73±3.1 pmol/l to 8.81±2.9 pmol/l, p = 0.018, nuts: from 7.29±2.9 pmol/l to 8.62±3.0 pmol/l, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group.

Conclusions

Although BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02227511","term_id":"NCT02227511"}}NCT02227511     

Region-Oriented and Staged Treatment Strategy in Reconstruction of Severe Cervical Contracture

Introduction

Severe cervical contracture after burns causes obvious impairment of neck movement and the aesthetic silhouette. Although various surgical techniques for treatment have been described, there is not a definitive strategy to guide treatment. Over the past 6 years, we have been utilizing a region-oriented and staged treatment strategy to guide reconstruction of severe cervical contracture. Satisfactory results have been achieved with this strategy.

Methods

The first stage of treatment focuses on the anterior cervical region and submental region. Procedures include cicatrix resection, contracture release, division and elevation of the platysma to form two platysma flaps, and skin grafting. Three to six months later, the second stage treatment is performed, which localize to the mental region. This includes scar resection, correction of the lower lip eversion, and reconstruction with free (para)scapular skin flap. Three subtypes of cervicomental angle that we proposed were measured as quantitative tool for evaluation of the reconstruction.

Results

24 patients who completed the treatment were reviewed. By the 3rd postoperative month, their CM angles changed significantly: the soft tissue CM angle was reduced from 135.0° ± 17.3° to 111.1° ± 11.3°, the osseous CM angle increased from 67.1° ± 9.0° to 90.5° ± 11.6° and the dynamic CM angle increased from 21.9° ± 8.7° to 67.4° ± 13.1°. 22 in 24 (91.7%) of these patients gained notable improvement of cervical motion and aesthetic contour.

Conclusions

Our results suggest that the region-oriented and staged treatment strategy can achieve satisfactory functional and aesthetic results, combining usage of both skin graft and skin flap while minimizing the donor site morbidity.     

The Safety of Using Body-Transmit MRI in Patients with Implanted Deep Brain Stimulation Devices

Background

Deep brain stimulation (DBS) is an established treatment for patients with movement disorders. Patients receiving chronic DBS provide a unique opportunity to explore the underlying mechanisms of DBS using functional MRI. It has been shown that the main safety concern with MRI in these patients is heating at the electrode tips – which can be minimised with strict adherence to a supervised acquisition protocol using a head-transmit/receive coil at 1.5T. MRI using the body-transmit coil with a multi-channel receive head coil has a number of potential advantages including an improved signal-to-noise ratio.

Study outline

We compared the safety of cranial MRI in an in vitro model of bilateral DBS using both head-transmit and body-transmit coils. We performed fibre-optic thermometry at a Medtronic ActivaPC device and Medtronic 3389 electrodes during turbo-spin echo (TSE) MRI using both coil arrangements at 1.5T and 3T, in addition to gradient-echo echo-planar fMRI exposure at 1.5T. Finally, we investigated the effect of transmit-coil choice on DBS stimulus delivery during MRI.

Results

Temperature increases were consistently largest at the electrode tips. Changing from head- to body-transmit coil significantly increased the electrode temperature elevation during TSE scans with scanner-reported head SAR 0.2W/kg from 0.45°C to 0.79°C (p<0.001) at 1.5T, and from 1.25°C to 1.44°C (p<0.001) at 3T. The position of the phantom relative to the body coil significantly impacted on electrode heating at 1.5T; however, the greatest heating observed in any position tested remained <1°C at this field strength.

Conclusions

We conclude that (1) with our specific hardware and SAR-limited protocol, body-transmit cranial MRI at 1.5T does not produce heating exceeding international guidelines, even in cases of poorly positioned patients, (2) cranial MRI at 3T can readily produce heating exceeding international guidelines, (3) patients with ActivaPC Medtronic systems are safe to be recruited to future fMRI experiments performed under the specific conditions defined by our protocol, with no likelihood of confound by inappropriate stimulus delivery.     

Comparison of the Effects of Flexion and Extension of the Thumb and Fingers on the Position and Cross-Sectional Area of the Median Nerve

Objective

To assess the separate effects of thumb and finger extension/flexion on median nerve position and cross-sectional area.

Methods

Ultrasonography was used to assess median nerve transverse position and cross-sectional area within the carpal tunnel at rest and its movement during volitional flexion of the individual digits of the hand. Both wrists of 165 normal subjects (11 men, 4 women, mean age, 28.6, range, 22 to 38) were studied.

Results

Thumb flexion resulted in transverse movement of the median nerve in radial direction (1.2±0.6 mm), whereas flexion of the fingers produced transverse movement in ulnar direction, which was most pronounced during flexion of the index and middle fingers (3.2±0.9 and 3.1±1.0 mm, respectively). Lesser but still statistically significant movements were noted with flexion of the ring finger (2.0±0.8 mm) and little finger (1.2±0.5 mm). Flexion of the thumb or individual fingers did not change median nerve cross-sectional area (8.5±1.1 mm²).

Conclusions

Volitional flexion of the thumb and individual fingers, particularly the index and middle fingers, produced significant transverse movement of the median nerve within the carpal tunnel but did not alter the cross-sectional area of the nerve. The importance of these findings on the understanding of the pathogenesis of the carpal tunnel syndrome and its treatment remains to be investigated.     

Effect of Serum Leptin on Weight Gain Induced by Olanzapine in Female Patients with Schizophrenia

Background

Olanzapine (OLZ) treatment is associated with a high risk of weight gain, and may cause abnormalities in glycolipid metabolism. Therefore, the underlying mechanism of OLZ-related weight gain is needed to clarify but not yet been adequately determined. In recent years, adipocytokines such as leptin, adiponectin, and tumor necrosis factor (TNF)-α, which play important roles in energy homeostasis, have been suggested as biomarkers of weight gain. Here, we determined if baseline plasma concentrations of leptin, adiponectin, and TNF-α predict weight gain following OLZ treatment.

Methods

We recruited 31 schizophrenia outpatients (12 men and 19 women, 28.8 ± 10.2 years old) that were unmedicated or on another antipsychotic monotherapy medication. Baseline body mass index (BMI) and plasma levels of leptin, adiponectin, and TNF-α were obtained. All patients started or were switched to OLZ monotherapy for a maximum of 1 year. BMI was also obtained at the endpoint.

Results

Mean BMI change following OLZ treatment was 2.1 ± 2.7 kg/m². BMI change from baseline to endpoint negatively-correlated with baseline leptin levels in female patients (r = −0.514, P = 0.024), but not male patients. Baseline adiponectin or TNF-α levels were not correlated with BMI change.

Conclusion

Baseline plasma leptin can have an effect on subsequent weight gain following OLZ treatment in female patients with schizophrenia.     

Intraocular Pressure Changes during Accommodation in Progressing Myopes,Stable Myopes and Emmetropes

Purpose

To investigate the changes of intraocular pressure (IOP) induced by 3-diopter (3 D) accommodation in progressing myopes, stable myopes and emmetropes.

Design

Cross-sectional study.

Participants

318 subjects including 270 myopes and 48 emmetropes.

Methods

195 progressing myopes, 75 stable myopes and 48 emmetropes participated in this study. All subjects had their IOP measured using iCare rebound tonometer while accommodative stimuli of 0 D and 3 D were presented.

Main Outcome Measures

IOP values without accommodation and with 3 D accommodation were measured in all subjects. Baseline IOPs and IOP changes were compared within and between groups.

Results

There was no significant difference in IOPs between progressing myopes, stable myopes and emmetropes when no accommodation was induced (17.47±3.46, 16.62±2.98 and 16.80±3.62 respectively, p>0.05). IOP experienced an insignificantly slight decrease after 3 D accommodation in three groups (mean change -0.19±2.16, -0.03±1.68 and -0.39±2.65 respectively, p>0.05). Subgroup analysis showed in progressing myopic group, IOP of children (<18 years old) declined with accommodation while IOP of adults (≥18 years) increased, and the difference was statistically significant (p = 0.008). However, after excluding the age factor, accommodation induced IOP changes of high progressing myopes (≤-6 D), low, moderate and non-myopes (>-6 D) was not significantly different after Bonferroni correction (p = 0.838).

Conclusions

Although no difference was detected between the baseline IOPs and accommodation induced IOP changes in progressing myopes, stable myopes and emmetropes, this study found accommodation could cause transient IOP elevation in adult progressing myopes.     

Excessive Weight Gain during the First Year of Peritoneal Dialysis Is Associated with Inflammation,Diabetes Mellitus,and a Rapid Decrease in Residual Renal Function

Objectives

Significant weight gain is a potential problem in most patients starting peritoneal dialysis (PD); however, few studies have explored the clinical effects of increased body weight (BW) in these patients. We evaluated the effect of excess weight gain during the first year after PD on residual renal function (RRF).

Methods

A total of 148 incident PD patients were analyzed in a longitudinal observational study. The mean duration of follow-up was 23.8 months. RRF was measured at baseline (within 1 month of starting PD) and thereafter at 6-month intervals for 2–3 years or until loss of RRF. BW was measured at the time of RRF measurement, and excess weight gain was defined as a BW increase over the median value (3.0%).

Results

The median 1-year increase in BW was 2.3kg (IQR, 1.01–4.58) or 3.0% (IQR, 1.13–5.31). The mean slope of RRF decline was –0.068 ± 0.053 mL/min/month/1.73m², and RRF loss developed in 48 patients at a mean follow-up time of 19.4 ± 6.8 months. Patients with BW increases > 3.0% showed significantly increased RRF decline rate compared to those without excess weight gain (p<0.001), and the BW increase (%/year) correlated significantly with higher hs-CRP levels and RRF decline rate. High systolic blood pressure, diabetes, large amount of proteinuria and excess BW gain significantly influenced the RRF decline rate. Also, it increased the risk of RRF loss by 4.17-fold (95% confidence intervals, 1.87–9.28; p<0.001).

Conclusions

Excess weight gain during the first year of PD was closely linked to systemic inflammation, diabetes and rapid decline in RRF.     

Serum Bile Acids in Repaired Tetralogy of Fallot: A Marker for Liver and Heart?

Background and Aims

Patients with repaired tetralogy of Fallot may develop chronic right ventricular dysfunction and hepatic congestion over time. We hypothesized that bile acid metabolism is altered in repaired tetralogy of Fallot patients and therefore sought to correlate right ventricular indices with serum bile acid levels.

Methods

Indexed right ventricular end diastolic volume, as assessed by cardiac magnetic-resonance imaging, was classified as <100ml/m² (Group 1, n = 5), 100–150ml/m² (Group 2, n = 18), and >150ml/m² (Group 3, n = 6) in 29 patients with repaired tetralogy of Fallot. Pulmonary regurgitation fraction and right ventricular ejection fraction were calculated. The serum bile acid profile, including 15 species, in these patients was determined by liquid chromatography coupled with mass spectrometry.

Results

Serum bile acid levels increased from Group 1 to Group 3 (2.5 ± 0.7; 4.1 ± 2.5; 6.0 ± 2.8 μmol/l, respectively) with significantly increased bile acid values in Group 3 compared to Group 1 (p≤0.05). In Group 3, but not in Group 1 and 2, a significant increase in glycine-conjugated bile acids was observed. Pulmonary regurgitation fraction increased (12 ± 1; 28 ± 16; 43 ± 3%, Groups 1–3, respectively) and right ventricular ejection fraction decreased (48.4 ± 6.4; 48.5 ± 6.5; 42.1 ± 5.3%, Groups 1–3, respectively) with rising indexed right ventricular end diastolic volume.

Conclusions

These preliminary results suggest that serum bile acid levels are positively correlated with indexed right ventricular end-diastolic volume in patients with repaired tetralogy of Fallot; however, this needs to be confirmed in a larger patient cohort.     

Prediabetes Phenotype Influences Improvements in Glucose Homeostasis with Resistance Training

Purpose

To determine if prediabetes phenotype influences improvements in glucose homeostasis with resistance training (RT).

Methods

Older, overweight individuals with prediabetes (n = 159; aged 60±5 yrs; BMI 33±4 kg/m²) completed a supervised RT program twice per week for 12 weeks. Body weight and composition, strength, fasting plasma glucose, 2-hr oral glucose tolerance, and Matsuda-Defronza estimated insulin sensitivity index (ISI) were assessed before and after the intervention. Participants were categorized according to their baseline prediabetes phenotype as impaired fasting glucose only (IFG) (n = 73), impaired glucose tolerance only (IGT) (n = 21), or combined IFG and IGT (IFG/IGT) (n = 65).

Results

Chest press and leg press strength increased 27% and 18%, respectively, following the 12-week RT program (both p<0.05). Waist circumference (-1.0%; pre 109.3±10.3 cm, post 108.2±10.6 cm) and body fat (-0.6%; pre 43.7±6.8%, post 43.1±6.8%) declined, and lean body mass (+1.3%; pre 52.0±10.4 kg, post 52.7±10.7 kg) increased following the intervention. Fasting glucose concentrations did not change (p>0.05) following the intervention. However, 2-hr oral glucose tolerance improved in those with IGT (pre 8.94±0.72 mmol/l, post 7.83±1.11 mmol/l, p<0.05) and IFG/IGT (pre 9.66±1.11mmol/l, post 8.60±2.00 mmol/l) but not in those with IFG (pre 6.27±1.28mmol/l, post 6.33± 1.55 mmol/l). There were no significant changes in ISI or glucose area under the curve following the RT program.

Conclusions

RT without dietary intervention improves 2-hr oral glucose tolerance in individuals with prediabetes. However, the improvements in glucose homeostasis with RT appear limited to those with IGT or combined IFG and IGT.

Trial Registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01112709","term_id":"NCT01112709"}}NCT01112709     

Efficacy and Safety of Sitagliptin Added to Insulin in Japanese Patients with Type 2 Diabetes: The EDIT Randomized Trial

Aims

To clarify the efficacy and safety of adding sitagliptin to insulin therapy in Japanese patients with suboptimally controlled type 2 diabetes (T2DM).

Study Design and Methods

This was a 24-week, prospective, randomized, open-labeled, controlled trial. Patients with T2DM who were suboptimally controlled despite receiving at least twice daily injection of insulin were enrolled in the study. The patients were randomized to continuation of insulin treatment (Insulin group) or addition of sitagliptin 50 to 100 mg daily to insulin treatment (Ins+Sita group). The primary outcome was change in HbA1c at week 24.

Results

Adding sitagliptin to insulin significantly reduced HbA1c from 7.9 ± 1.0% at baseline to 7.0 ± 0.8% at week 24 (P <0.0001), while there was no significant change in HbA1c in the Insulin group (7.8 ± 0.7% vs. 7.8 ± 1.1%, P = 0.32). The difference in HbA1c reduction between the groups was 0.9% (95% confidence interval, 0.4 to 1.5, P = 0.01). There was no significant weight gain in either group. Incidence of hypoglycemia was significantly reduced in the Ins+Sita group compared with the Insulin group. Treatment satisfaction was improved in the Ins+Sita group. Baseline HbA1c level and beta cell function were associated with the magnitude of reduction in HbA1c in the Ins+Sita group.

Conclusion

Adding sitagliptin to insulin reduced HbA1c without weight gain or increase in hypoglycemia, and improved treatment satisfaction in Japanese patients with T2DM who were suboptimally controlled despite at least twice daily injection of insulin.

Trial Registration

The University Hospital Medical Information Network (UMIN) Clinical Trials Registry UMIN000004678     

The Effect of Neutral Peritoneal Dialysis Solution with Low Glucose-Degradation-Product on the Fluid Status and Body Composition – A Randomized Control Trial

Background

Previous studies report conflicting results on the benefit of peritoneal dialysis (PD) patients treated with low glucose degradation product (GDP) solution. The effects of low GDP solution on body fluid status and arterial pulse wave velocity (PWV) have not been studied.

Methods

We randomly assigned 68 incident PD patients to low GDP (Intervention Group) or conventional solutions (Control Group); 4 dropped off before they received the assigned treatment. Patients were followed for 52 weeks for changes in ultrafiltration, residual renal function, body fluid status and arterial PWV.

Result

After 52 weeks, Intervention Group had higher overhydration (3.1 ± 2.6 vs 1.9 ± 2.2 L, p = 0.045) and extracellular water volume (17.7 ± 3.9 vs 15.8 ± 3.1 L, p = 0.034) than Control Group. There was no significant difference in PWV between groups. There was no significant difference in residual renal function between the Groups. Intervention Group had lower ultrafiltration volume than Control Group at 4 weeks (0.45 ± .0.61 vs 0.90 ± 0.79 L/day, p = 0.013), but the difference became insignificant at later time points. Intervention Group had lower serum CRP levels than Control Group (4.17 ± 0.77 vs 4.91 ± 0.95 mg/dL, p < 0.0001).

Conclusion

Incident PD patients treated with low GDP solution have less severe systemic inflammation but trends of less ultrafiltration, and more fluid accumulation. However, the effects on ultrafiltration and fluid accumulation disappear with time. The long term effect of low GDP solution requires further study.

Trial Registration

ClinicalTrials.gov NCT00966615     

Very Preterm Infants Failing CPAP Show Signs of Fatigue Immediately after Birth

Objective

To investigate the differences in breathing pattern and effort in infants at birth who failed or succeeded on continuous positive airway pressure (CPAP) during the first 48 hours after birth.

Methods

Respiratory function recordings of 32 preterm infants were reviewed of which 15 infants with a gestational age of 28.6 (0.7) weeks failed CPAP and 17 infants with a GA of 30.1 (0.4) weeks did not fail CPAP. Frequency, duration and tidal volumes (VT) of expiratory holds (EHs), peak inspiratory flows, CPAP-level and FiO₂-levels were analysed.

Results

EH incidence increased <6 minutes after birth and remained stable thereafter. EH peak inspiratory flows and VT were similar between CPAP-fail and CPAP-success infants. At 9-12 minutes, CPAP-fail infants more frequently used smaller VTs, 0-9 ml/kg and required higher peak inspiratory flows. However, CPAP-success infants often used large VTs (>9 ml/kg) with higher peak inspiratory flows than CPAP-fail infants (71.8 ± 15.8 vs. 15.5 ± 5.2 ml/kg.s, p <0.05). CPAP-fail infants required higher FiO₂ (0.31 ± 0.03 vs. 0.21 ± 0.01), higher CPAP pressures (6.62 ± 0.3 vs. 5.67 ± 0.26 cmH₂O) and more positive pressure-delivered breaths (45 ± 12 vs. 19 ± 9%) (p <0.05)

Conclusion

At 9-12 minutes after birth, CPAP-fail infants more commonly used lower VTs and required higher peak inspiratory flow rates while receiving greater respiratory support. VT was less variable and larger VT was infrequently used reflecting early signs of fatigue.     

Acute Dietary Nitrate Supplementation and Exercise Performance in COPD: A Double-Blind,Placebo-Controlled,Randomised Controlled Pilot Study

Background

Dietary nitrate supplementation can enhance exercise performance in healthy people, but it is not clear if it is beneficial in COPD. We investigated the hypotheses that acute nitrate dosing would improve exercise performance and reduce the oxygen cost of submaximal exercise in people with COPD.

Methods

We performed a double-blind, placebo-controlled, cross-over single dose study. Subjects were randomised to consume either nitrate-rich beetroot juice (containing 12.9mmoles nitrate) or placebo (nitrate-depleted beetroot juice) 3 hours prior to endurance cycle ergometry, performed at 70% of maximal workload assessed by a prior incremental exercise test. After a minimum washout period of 7 days the protocol was repeated with the crossover beverage.

Results

21 subjects successfully completed the study (age 68±7years; BMI 25.2±5.5kg/m²; FEV₁ percentage predicted 50.1±21.6%; peak VO₂ 18.0±5.9ml/min/kg). Resting diastolic blood pressure fell significantly with nitrate supplementation compared to placebo (-7±8mmHg nitrate vs. -1±8mmHg placebo; p = 0.008). Median endurance time did not differ significantly; nitrate 5.65 (3.90–10.40) minutes vs. placebo 6.40 (4.01–9.67) minutes (p = 0.50). However, isotime oxygen consumption (VO₂) was lower following nitrate supplementation (16.6±6.0ml/min/kg nitrate vs. 17.2±6.0ml/min/kg placebo; p = 0.043), and consequently nitrate supplementation caused a significant lowering of the amplitude of the VO₂-percentage isotime curve.

Conclusions

Acute administration of oral nitrate did not enhance endurance exercise performance; however the observation that beetroot juice caused reduced oxygen consumption at isotime suggests that further investigation of this treatment approach is warranted, perhaps targeting a more hypoxic phenotype.

Trial Registration

ISRCTN Registry ISRCTN66099139     

Fasting Plasma Insulin at 5 Years of Age Predicted Subsequent Weight Increase in Early Childhood over a 5-Year Period—The Da Qing Children Cohort Study

Background

The association between hyperinsulinemia and obesity is well known. However, it is uncertain especially in childhood obesity, if initial fasting hyperinsulinemia predicts obesity, or obesity leads to hyperinsulinemia through insulin resistance.

Objective

To investigate the predictive effect of fasting plasma insulin on subsequent weight change after a 5-year interval in childhood.

Methods

424 Children from Da Qing city, China, were recruited at 5 years of age and followed up for 5 years. Blood pressure, anthropometric measurements, fasting plasma insulin, glucose and triglycerides were measured at baseline and 5 years later.

Results

Fasting plasma insulin at 5 years of age was significantly correlated with change of weight from 5 to 10 years (ΔWeight). Children in the lowest insulin quartile had ΔWeight of 13.08±0.73 kg compare to 18.39±0.86 in the highest insulin quartile (P<0.0001) in boys, and similarly 12.03±0.71 vs 15.80±0.60 kg (P<0.0001) in girls. Multivariate analysis showed that the predictive effect of insulin at 5 years of age on subsequent weight gain over 5 years remained statistically significant even after the adjustment for age, sex, birth weight, TV-viewing time and weight (or body mass index) at baseline. By contrast, the initial weight at 5 years of age did not predict subsequent changes in insulin level 5 years later. Children who had both higher fasting insulin and weight at 5 years of age showed much higher levels of systolic blood pressures, fasting plasma glucose, the homeostasis model assessment for insulin resistance (HOMA-IR) and triglycerides at 10 years of age.

Conclusions

Fasting plasma insulin at 5 years of age predicts weight gain and cardiovascular risk factors 5 year later in Chinese children of early childhood, but the absolute weight at 5 years of age did not predict subsequent change in fasting insulin.     

Measurement Variability of Persistent Pulmonary Subsolid Nodules on Same-Day Repeat CT: What Is the Threshold to Determine True Nodule Growth during Follow-Up?

Purpose

To assess the measurement variability of subsolid nodules (SSNs) in follow-up situations and to compare the degree of variability between measurement metrics.

Methods

Two same-day repeat-CT scans of 69 patients (24 men and 45 women) with 69 SSNs were randomly assigned as initial or follow-up scans and were read by the same (situation 1) or different readers (situation 2). SSN size and solid portion size were measured in both situations. Measurement variability was calculated and coefficients of variation were used for comparisons.

Results

Measurement variability for the longest and average diameter of SSNs was ±1.3 mm (±13.0%) and ±1.3 mm (±14.4%) in situation 1, and ±2.2 mm (±21.0%) and ±2.1 mm (±21.3%) in situation 2, respectively. For solid portion, measurement variability on lung and mediastinal windows was ±1.2 mm (±27.1%) and ±0.8 mm (±24.0%) in situation 1, and ±3.7 mm (±61.0%) and ±1.5 mm (±47.3%) in situation 2, respectively. There were no significant differences in the degree of variability between the longest and average diameters and between the lung and mediastinal window settings (p>0.05). However, measurement variability significantly increased when the follow-up and initial CT readers were different (p<0.001).

Conclusions

A cutoff of ±2.2 mm can be reliably used to determine true nodule growth on follow-up CT. Solid portion measurements were not reliable in evaluating SSNs’ change when readers of initial and follow-up CT were different.