Mean Pulse Amplitude Research Articles

Relationship between Intraocular Pressure Fluctuation and Visual Field Progression Rates in the United Kingdom Glaucoma Treatment Study

To investigate whether intraocular pressure (IOP) fluctuation is associated independently with the rate of visual field (VF) progression in the United Kingdom Glaucoma Treatment Study. Randomized, double-masked, placebo-controlled multicenter trial. Participants with ≥5 VFs (213 placebo, 217 treatment). Associations between IOP metrics and VF progression rates (mean deviation [MD] and five fastest locations) were assessed with linear mixed models. Fluctuation variables were mean Pascal ocular pulse amplitude (OPA), standard deviation (SD) of diurnal Goldmann IOP (diurnal fluctuation), and SD of Goldmann IOP at all visits (long-term fluctuation). Fluctuation values were normalized for mean IOP to make them independent from the mean IOP. Correlated nonfluctuation IOP metrics (baseline, peak, mean, supine, and peak phasing IOP) were combined with principal component analysis, and principal component 1 (PC1) was included as a covariate. Interactions between covariates and time from baseline modeled the effect of the variables on VF rates. Analyses were conducted separately in the two treatment arms. Associations between IOP fluctuation metrics and rates of MD and the five fastest test locations. In the placebo arm, only PC1 was associated significantly with the MD rate (estimate, -0.19 dB/year [standard error (SE), 0.04 dB/year]; P < 0.001), whereas normalized IOP fluctuation metrics were not. No variable was associated significantly with MD rates in the treatment arm. For the fastest five locations in the placebo group, PC1 (estimate, -0.58 dB/year [SE, 0.16 dB/year]; P < 0.001), central corneal thickness (estimate, 0.26 dB/year [SE, 0.10 dB/year] for 10 μm thicker; P= 0.01) and normalized OPA (estimate, -3.50 dB/year [SE, 1.04 dB/year]; P= 0.001) were associated with rates of progression; normalized diurnal and long-term IOP fluctuations were not. In the treatment group, only PC1 (estimate, -0.27 dB/year [SE, 0.12 dB/year]; P= 0.028) was associated with the rates of progression. No evidence supports that either diurnal or long-term IOP fluctuation, as measured in clinical practice, are independent factors for glaucoma progression; other aspects of IOP, including mean IOP and peak IOP, may be more informative. Ocular pulse amplitude may be an independent factor for faster glaucoma progression. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

326 Sleep Stages Variation in Intracranial Pressure and Pulse Amplitude

INTRODUCTION: It is thought that CSF pulsatility has an important role in brain physiology during sleep. Yet few studies have looked into changes of ICP and pulsatility during sleep. METHODS: A single centre prospective cohort study. Patients undergoing 24 h ICP monitoring for suspected CSF dynamic disorders underwent concomitant polysomnography. Clinical and radiological presentation were derived from the patient’s records. Aggregate mean ICP and pulse amplitude (mPA) values were recorded for each sleep stage. Sleep staging was performed in conformity with the AASM guidelines. Within subject values were compared using repeated-measures, one-way ANOVA. Post-hoc paired t-tests were used to compare sleep stages between groups corrected for multiple comparisons (Benjamini-Hochberg method). RESULTS: A total of 12 patients (10 females, 2 males; mean age 40.8 years, SD+/- 12.9) with complete data were analysed. There were significant differences in mean ICP between sleep stages (F(3,33) = 10.7, p &lt; 0.00001). Post-hoc paired t-tests revealed significant differences between rapid eye movement (REM; mean ICP 14.4 mmHg) and all other sleep stages (mean ICP/N1 = 12.0 mmHg, t = -3.6, p = 0.004; ICP/N2 = 11.8 mmHg, t = -4.3, p = 0.001; ICP/N3 = 12.3 mmHg, t = -3.5, p = 0.004). Significant differences were also found in mPA between sleep stages (F(3,33) = 5.7, p = 0.003) confirmed on post-hoc paired t-tests: REM (mean mPA 5.5 mmHg and all other sleep stages: mPA/N1 = 4.7 mmHg, t = -2.3, p = 0.04; mPA/N2 = 4.3 mmHg, t = -2.7, p = 0.02; mPA/N3 = 4.5 mmHg, t = -2.3, p = 0.04). CONCLUSIONS: REM is characterized by higher ICP and mPA values, result confirmed in near-normal patients included in this cohort.

OR14-4 Acute sleep disruption does not diminish pulsatile growth hormone secretion in pubertal children

Abstract Context: Growth hormone (GH) plays a critical role in glucose homeostasis and linear growth during childhood. GH secretion is controlled by multiple neurotransmitters and hormones. Sleep is also a powerful stimulus for GH secretion. In children, GH pulses occur after sleep onset in association with slow-wave sleep (SWS), but it is unclear if undisrupted sleep is required for normal GH secretion. Given the rising incidence of pediatric sleep disorders such as obstructive sleep apnea (OSA) that cause sleep fragmentation, it is critical to determine whether sleep fragmentation during childhood may dysregulate the somatotropic axis. Objective To quantify how undisrupted vs fragmented sleep affects GH secretion in children. Methods Pubertal subjects (10 M, 9 F; 9.1-14.4 yrs) were randomized to two overnight polysomnographic studies with frequent blood sampling (q10min) to measure GH: fourteen were healthy subjects studied with or without SWS disruption via auditory stimuli (3 sec, 1500 Hz tones, 40-100 dB followed by 18 sec of a 75 dB noise simulating a knock on the door) and five were subjects with OSA studied with or without prescribed continuous positive airway pressure (CPAP); the latter condition was expected to have sleep fragmentation due to untreated OSA. GH pulses were identified using sparse deconvolution. Studies without auditory stimuli or when using CPAP were combined and analyzed as 'undisrupted sleep'. The relationship between GH pulse rate per hour and sleep stage was evaluated using Poisson generalized estimating equations. Results In SWS disruption studies, an average of 77.51 ± 13.61 (range 23-190) auditory stimuli were delivered, causing a 40.02 ± 7.78% decrease in SWS in favor of lighter sleep stages. In subjects with OSA, CPAP withdrawal caused a slight increase in the apnea hypopnea index (1.08 ± 0.10 vs. 2.20 ± 1.70 events/hour of sleep, p=0.07) with no change in sleep stage durations. During undisrupted sleep, subjects had an average of 0.91 ± 0.067 GH pulses/hour with a mean pulse amplitude of 10.03 ± 1.00 ng/mL and mean basal secretion rate of 0.26 ± 0.10 ng/ml per min. GH pulses occurred more frequently during SWS (2.3 pulses/hour SWS, amplitude 9.92 ± 2.59 ng/mL) than during any other sleep stage (P &amp;lt; 0.001). Neither form of sleep disruption affected the distribution of GH pulses across sleep stages, GH pulse amplitude and frequency, nor basal GH secretion. Conclusion In children, nocturnal GH pulses are temporally associated with SWS. However, neither acute fragmentation of SWS nor nocturnal arousals from OSA altered basal or pulsatile GH secretion, indicating that somatotrophic axis activity is preserved in the face of acute sleep disruption in children. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

Effect of position on intracranial pressure and compliance: a cross-sectional study including 101 patients.

A better understanding of the effect of position on intracranial pressure (ICP) and compliance is important for the development of treatment strategies that can restore normal cerebrospinal fluid (CSF) dynamics. There is limited knowledge on the effect of position on intracranial compliance. In this cross-sectional study the authors tested the association of pulse amplitude (PA) with position and the day/night cycle. Additionally, they describe the postural ICP and PA changes of patients with "normal" ICP dynamics. This single-center retrospective study included patients with suspected and/or confirmed CSF dynamics abnormalities who had been examined with elective 24-hour ICP monitoring between October 2017 and September 2019. Patients had been enrolled in a short exercise battery including four positions: supine, lumbar puncture position in the left lateral decubitus position, sitting, and standing. Each position was maintained for 2 minutes, and mean ICP and PA were calculated for each position. The 24-hour day and night median ICP and PA data were also collected. Linear regression models were used to test the correlation of PA with position and day/night cycle. All linear regressions were corrected for confounders. The postural ICP monitoring results of patients without obvious ICP dynamics abnormality were summarized. One hundred one patients (24 males and 77 females) with a mean age of 39 ± 13years (mean ± standard deviation) were included in the study. The adjusted linear regression models demonstrated a significant association of ICP with position and day/night cycle, with upright (sitting and standing) and day ICP values lower than supine and night ICP values. The adjusted linear regression model was also significant for the association of PA with position and day/night cycle, with upright and day PA values higher than supine and night PA results. These associations were confirmed for patients with and without shunts. Patients without clear ICP dynamics abnormality had tighter control of their postural ICP changes than the other patients; however, the difference among groups was not statistically significant. This is the largest study investigating the effect of postural changes on intracranial compliance. The results of this study suggest that PA, as well as ICP, is significantly associated with posture, increasing in upright positions compared to that while supine. Further studies will be needed to investigate the mechanism behind this association.

Effects of the Isolated and Combined Ablation of Growth Hormone and IGF-1 Receptors in Somatostatin Neurons.

Hypophysiotropic somatostatin (SST) neurons in the periventricular hypothalamic area express growth hormone (GH) receptor (GHR) and are frequently considered as the key neuronal population that mediates the negative feedback loop controlling the hypothalamic-GH axis. Additionally, insulin-like growth factor-1 (IGF-1) may also act at the hypothalamic level to control pituitary GH secretion via long-loop negative feedback. However, to the best of our knowledge, no study so far has tested whether GHR or IGF-1 receptor (IGF1R) signaling specifically in SST neurons is required for the homeostatic control of GH secretion. Here we show that GHR ablation in SST neurons did not impact the negative feedback mechanisms that control pulsatile GH secretion or body growth in male and female mice. The sex difference in hepatic gene expression profile was only mildly affected by GHR ablation in SST neurons. Similarly, IGF1R ablation in SST neurons did not affect pulsatile GH secretion, body growth, or hepatic gene expression. In contrast, simultaneous ablation of both GHR and IGF1R in SST-expressing cells increased mean GH levels and pulse amplitude in male and female mice, and partially disrupted the sex differences in hepatic gene expression. Despite the increased GH secretion in double knockout mice, no alterations in body growth and serum or liver IGF-1 levels were observed. In summary, GHR and IGF1R signaling in SST neurons play a redundant role in the control of GH secretion. Furthermore, our results reveal the importance of GH/IGF-1 negative feedback mechanisms on SST neurons for the establishment of sex differences in hepatic gene expression profile.

Pragmatic method for fast programming of hybrid photon counting detectors

It is now been over 15 years since Hybrid Photon Counting Detectors (HPCD) became one of the standard position-sensitive detectors for synchrotron light sources and X-ray detection applications. This is mainly due to their single-photon sensitivity over a high dynamic energy range and electronic noise suppression thanks to energy thresholding. To reach those performances, all HPCD pixels must feature the same electrical response against photons of the same energy. From the analysis of a monochromatic beam, in case of an ideal HPCD detector, it would be sufficient to apply a fixed voltage threshold among all pixels, positioned at half of the mean pulse amplitude to count every photon above the threshold. However, in practical cases, it must be considered that noise baselines from all pixels are not always strictly located at the same voltage level but can be spread over some voltage ranges. To address this kind of issue, most of all HPCDs apply a conventional threshold equalization method, that mainly relies on three steps; the setting of a global threshold at an arbitrary value, the identification of pixels noise baseline around that global threshold through an in-pixel threshold trimmer, and the computation of the required threshold offsets for setting all pixels at their own noise baseline at the same time. However, in case of a first-time use of an HPCD prototype, the threshold equalization might be biased by parameters that are wrongly set. Those biases can sometimes be characterized by the inability to localize some pixel noise baselines, which could be outside the voltage range of the threshold trimmer. The recovery of those biased pixels could be performed by changing the position of the global threshold, or by increasing the voltage range of the threshold trimmer. Unfortunately, both solutions could be time consuming due to the lack of information on the required steps for recovering all noise baselines. In order to overcome this issue in a reasonable time, this work introduces a pragmatic method that can be applied to HPCDs for an early and effective identification of appropriate pixels’ parameters, avoiding the need to test a high number of pixels configurations. The application of this method, at the early stage of the HPCD calibration, may drastically reduce the investigation time for finding the optimal operating parameters of HPCD prototypes.

Effect of Gas-Mixture Ratio on the Characteristics of Positive DC Corona Discharge in SF6/N2 Gas Mixtures

The characteristics of positive DC corona discharge in SF6/N2 gas mixtures under different gas-mixture ratios are investigated with a needle-to-plane electrode configuration. With increasing applied voltage, a discharge-stage transition process including the Townsend stage, streamer-pulse stage, brush-pulse stage and breakdown stage is observed. The variation in current-pulse characteristics, including pulse-time parameters, mean pulse amplitude and pulse-repetition rate, is investigated under different gas-mixture ratios. The pulse-time parameters are not affected by gas-mixture ratio. The pulse-repetition rate increases with the increase of SF6 concentration and mean current, ranging from hundreds of kilohertz to thousands of kilohertz. The streamer-pulse amplitude increases with increasing SF6 concentration. With increasing mean current, the small-amplitude brush pulses become dominant, thus the mean pulse amplitude decreases. In order to further explore the influence mechanism of gas-mixture ratio on positive corona discharge, a fluid model of positive corona discharge is developed and relevant simulations show the formation process of current pulse, and verify the validity of the pulse characteristics changing with gas-mixture ratio.

Microcirculatory Flux and Pulsatility in Arterial Leg Ulcers is Increased by Intermittent Neuromuscular Electrostimulation of the Common Peroneal Nerve

Neuromuscular electrical stimulator (NMES) devices increase blood flow to the lower limb by a process of intermittent muscular contraction initiated by a transdermal stimulus to the common peroneal nerve. However, its effects on localized microvascular blood supply to lower limb wounds are unknown. This study is a single-center open label study measuring the effect of neuromuscular stimulation of the common peroneal nerve on the microvascular blood flow within the wound bed of arterial leg ulcers. Eights patients with ischemic lower limb wounds had an NMES (geko™) applied to the common peroneal nerve. Baseline and intervention analysis of blood flow to the wound bed and edge was performed using Laser Speckle Contrast Imaging. Mean flow (flux) and pulse amplitude (pulsatility) were measured. Stimulation of the common peroneal nerve with the NMES resulted in a significantly increased flux and pulsatility in both the wound bed and the wound edge in all 8 patients. Neuromuscular electrical stimulation immediately increases microcirculatory blood flow to the wound bed and edge in patients with ischemic lower limb wounds. These data may provide mechanistic insight into the clinical efficacy of NMES in healing wounds. www.clinicaltrials.gov NCT03186560.

Intracranial pressure and compliance in hypoxic ischemic brain injury patients after cardiac arrest

IntroductionIn hypoxic ischemic brain injury (HIBI), increased intracranial pressure (ICP) can ensue from cerebral edema stemming from cytotoxic and vasogenic mechanisms. Downstream sequelae of restricted cerebral blood flow lead to neurologic braindeath. There is limited data characterizing the temporal trends and patterns of ICP and compliance in human HIBI patients. MethodsPatients underwent invasive ICP monitoring with a parenchymal probe (Camino) and were managed with a tier-based management algorithm for elevated ICP. Data pertaining to mean arterial pressure (MAP), ICP, brain tissue oxygenation (PbtO2), end tidal carbon dioxide (ETCO2), core body temperature and RAP (moving correlation coefficient between mean ICP and its mean pulse amplitude) as a measure of intracranial compliance were recorded in the ICM + software. Data pertaining to ICP lowering interventions was also collected. ResultsTen patients were included with a median age of 47 (range 20–71) and seven were male (7/10). The mean ICP was 14 mmHg (SD 11) and time of ICP> 20 mmHg was 22% (range 0–100). The mean MAP, ETCO2 and temperature were 89 mmHg (SD 13), 31 mmHg (SD 7), 35.7 °C (SD 0.9), respectively. The mean RAP was 0.58 (SD 0.34) and time of RAP > 0.4 was 78% (range 57–97). There were no significant relationships between ETCO2 and temperature with ICP. ConclusionsIn our cohort, HIBI was characterized by normal ICP but with limited intracranial compliance. However, significant in between patient heterogeneity exists with respect to temporal patterns of intracranial pressure — volume relationships in HIBI.Trial registration: clinicaltrials.gov (NCT03609333).

SAT-208 Effects of Metabolic and Psychological Stressors on Serum 24-Hour Cortisol and Luteinizing Hormone

Exercising women with functional hypothalamic amenorrhea (FHA) experience disrupted luteinizing hormone pulsatility which has been linked to low energy availability. While the susceptibility to life stressors in also linked to reproductive axis suppression, the contribution of psychosocial stress to FHA in exercising women is unclear. Our aim was to prospectively determine the relations between indicators of psychosocial and metabolic stressors on the change in LH pulse dynamics during a three-month diet and exercise intervention causing moderate weight loss in previously untrained, ovulatory, collage age women studied across an academic year. We also explored the potential role of cortisol as an indicator of both metabolic and psychosocial stress in the change in LH. This is a secondary analysis from a previously published randomized, controlled trial demonstrating the causal role of low energy availability in the disruption of the menstrual cycle. Here, we report on 21 women aged (18 to 24 yrs), BMI (21.7± 1.9 kg/m2), aerobic capacity (37.5 ± 5.3 ml/kg/min) who completed a baseline menstrual cycle and three intervention menstrual cycles of a controlled diet (55% carbohydrates, 30% protein, 15% fat) and supervised aerobic exercise (5 days/wk, 30-90 min/day, 60-80% maximum heart rate). We assessed anthropometrics, aerobic capacity, psychosocial stress (Perceived Stress Scale), and metabolic hormones throughout the intervention. 24 hour LH pulse dynamics (q10 min) and diurnal patterns of cortisol (q60 min) were determined in the early follicular phase prior to the intervention and in the follicular phase of the 3rd intervention cycle or in the post intervention cycle. Pre to post comparisons were determined with paired t-tests, and Pearson bivariate correlations assessed associations. Subjects lost weight pre=57.8±4.9 kg to post=55.0±4.6 kg (p<0.001) and gained aerobic capacity pre=37.5 ± 5.3 ml/kg/min to post= 42.3 ± 5.9 ml/kg/min (p=.003). LH pulse frequency declined pre=0.79±0.23 pulses/hr to post=0.60±.29 pulses/hr (p=0.014), but mean LH and pulse amplitude were unchanged. 24 hour cortisol area under the curve increased significantly from pre=6716 ±3839 µg*day/dL to post=8515 ±2259 µg*day/dL (p=0.003). Increases in cortisol AUC were associated with a decline in LH pulse frequency R=-0.472; (p=0.048). The change in PSS was not associated with the change in LH or the change in cortisol. Body weight declines were associated with increases in cortisol AUC R= -0.473, (p=0.03) and the decline in LH pulse frequency R= 0.523; (p=0.026). These results suggest that the initial perturbation of LH pulsatility with moderate diet and exercise is largely metabolically driven and not influenced by individual responses to life stressors experienced across the academic year.

Harmonic Summing Improves Pulsar Detection Sensitivity: A Probability Analysis

Abstract The practical application of the harmonic summing technique in the power-spectrum analysis for searching pulsars has exhibited the technique’s effectiveness. In this paper, theoretical verification of harmonic summing considering power’s noise-signal probability distribution is given. With the top-hat and the modified von Mises pulse profile models, contours along which spectra total power is expected to exceed the 3σ detection threshold with 0.999 confidence corresponding to m = 1, 2, 4, 8, 16, or 32 harmonics summed are given with respect to the mean pulse amplitude and the pulse duty cycle. Optimized numbers of harmonics summed relative to the duty cycles are given. The routine presented builds a theoretical estimate of the minimum detectable mean flux density, i.e., sensitivity, under the power-spectrum searching method.

Pulsatile versus non-pulsatile tinnitus in idiopathic intracranial hypertension.

Tinnitus is a symptom commonly associated with idiopathic intracranial hypertension (IIH) that can have a profound effect on quality of life. We aim to determine tinnitus symptom response after dural venous sinus stenting (DVSS) or CSF diversion with a shunt, in patients with both pulsatile (PT) and non-pulsatile tinnitus (NPT). Single-centre cohort of IIH patients (2006-2016) who underwent 24-h ICP monitoring (ICPM). An un-paired t test compared ICP and pulse amplitude (PA) values in IIH patients with PT vs. NPT. We identified 59 patients with IIH (56 F:3 M), mean age 32.5 ± 9.49years, 14 of whom suffered from tinnitus. Of these 14, seven reported PT and seven reported NPT. Patients with tinnitus had a mean 24-h ICP and PA of 9.09 ± 5.25mmHg and 6.05 ± 1.07mmHg respectively. All 7 patients with PT showed symptom improvement or resolution after DVSS (n = 4), secondary DVSS (n = 2) or shunting (n = 1). In contrast, of the 7 with NPT, only 1 improved post intervention (DVSS), despite 2 patients having shunts and 5 having DVSS. NPT and PT were equally as common in our group of IIH patients. DVSS appears to be an effective management option for IIH patients with a clear history of pulsatile tinnitus. However, non-pulsatile tinnitus was more persistent and did not respond well to either DVSS or CSF diversion.

Role of progesterone concentrations during early follicular development in beef cattle: I. Characteristics of LH secretion and oocyte quality

Objective was to investigate the effect of different progesterone (P4) concentrations during early follicular development on luteinizing hormone (LH) secretion and oocyte characteristics in beef cows. Primiparous cows (n = 24) were estrous pre-synchronized and follicular ablation was performed (d 0) 6 days following the time of ovulation. At the time of follicular ablation, cows were assigned to either: 1) high P4 treatment - HiP4; a new CIDR was inserted on d 0 to supplement P4 from the existing corpus luteum [CL], or 2) low P4 treatment - LoP4; a previously-used CIDR and two doses of PGF 8 to 12 h apart were given on d 0. Concentrations of P4 were greater (P < 0.01) in the cows of the HiP4 than LoP4 group on d 1.5, 2.5, and 3.5. Peripheral concentrations of E2 were greater (P < 0.05) in the cows of the LoP4 than HiP4 group on d 2.5 and 3.5. Frequency of LH pulses was greater (P < 0.05) in the LoP4 than HiP4 group on d 2.5, but mean LH concentration and pulse amplitude did not differ between treatments. Number of follicles aspirated per cow, total oocytes recovered, recovery rate, percentage of oocytes graded 1 to 3, oocyte diameter, percentage BCB+ oocytes, and relative abundance of oocyte mRNA for FST did not differ (P > 0.10) between treatments. In conclusion, lower P4 concentrations during early follicular development resulted in increased LH pulse frequency and E2 concentrations, but did not affect characteristics of oocyte developmental competence.

Usefulness of Pulse Amplitude Changes During the Valsalva Maneuver Measured Using Finger Photoplethysmography to Identify Elevated Pulmonary Capillary Wedge Pressure in Patients With Heart Failure

The pulse amplitude ratio, the ratio of pulse pressure at the end of a Valsalva maneuver to before the onset of Valsalva, correlates with filling pressure. This study aimed to noninvasively estimate cardiac filling pressure in patients with heart failure. We developed a noninvasive handheld device to measure pulse amplitude ratio using finger photoplethysmography. In 69 patients who underwent right heart catheterization, photoplethysmography waveforms were recorded during a standardized Valsalva maneuver, and in 60 of these patients, pulse amplitude ratio was able to be calculated. Pulse amplitude ratio correlated with pulmonary capillary wedge pressure (PCWP) (r = 0.58, p <0.0001), particularly among those subjects with reduced ejection fraction (r = 0.60, p = 0.002, n = 25). A multivariable linear regression model for PCWP including pulse amplitude ratio, age, body mass index, systolic blood pressure, diastolic blood pressure, and heart rate yielded an R2 of 0.54. Difference in mean pulse amplitude ratio for subjects with a PCWP ≤15 mm Hg versus >15 mm Hg was statistically significant (p <0.0001, area under receiver operating characteristics curve 0.79 [0.66, 0.92]). Pulse amplitude ratio ≥0.55 predicted PCWP >15 mm Hg with 73% sensitivity and 77% specificity. Pulse amplitude ratio also increased by an average of 0.03 with a leg raise maneuver (p = 0.05, n = 36). In conclusion, we demonstrate that noninvasively measured response to the Valsalva maneuver in patients with HF can estimate PCWP and also detect changes within a single patient.

Abstract 160: Multiscale Entropy of Photoplethysmographic Pulse Amplitudes of Bilateral Fingertips Varies by Hand Dominance and Diabetes Status

Objective: Multiscale entropy (MSE) of photoplethysmographic (PPG) pulse amplitudes may reflect cardiovascular health. In addition, poor glycemic control and weak handgrip strength are related to microvascular dysfunction in diabetes. We hypothesized that MSE of PPG pulse amplitudes between dominant and non-dominant hand may differ by diabetes status. Methods: Of a middle-to-old aged and right hand-dominant population free of prior cardiovascular disease, we matched age, sex, and weight to select the unaffected (no type 2 diabetes, n =36), the well-controlled diabetes (HbA1c &lt;8%, n =22), and the poorly-controlled diabetes (HbA1c ≥8%, n =22) groups. MSEs were calculated from simultaneous consecutive 1,500 resting PPG pulse amplitudes of bilateral index fingers. The small- and large-scale MSEs were defined as the average of scales 1 to 3 (MSE 1-3 ) and scales 4 to 10 (MSE 4-10 ), respectively. Intra- and inter-groups comparisons were performed by 1- and 2-sample t tests. Results: The inter- and intra-groups mean pulse amplitudes did not differ. In contrast, the pulse wave velocity was higher in the two diabetes groups, but was similar between two hands in each group. The dominant hand MSE 4-10 was lower in the poorly-controlled diabetes compared with the unaffected and well-controlled diabetes groups (1.25 vs. 1.52 and 1.49, p=0.001 and 0.017, respectively); whereas the non-dominant hand MSE 4-10 was lower in the well- and poorly-controlled diabetes groups than the unaffected (1.31 and 1.26 vs. 1.54, p=0.007 and 0.002 respectively). There was no intra-groups difference in MSE 4-10 , but a higher MSE 1-3 of dominant hand than that of non-dominant hand in the well-controlled diabetes (1.30 vs. 1.07, p=0.05). Conclusion: Diabetes status and hand activity are related to the MSE of PPG pulse amplitudes. The MSE indexes differed between two hands with euglycemia indicated that local physical inactivity might be an independent contributor to diabetic microvascular dysfunction.

Does aqueductal stenosis influence the lumbar infusion test in normal-pressure hydrocephalus?

Late-onset idiopathic aqueductal stenosis may present with clinical features indistinct from idiopathic normal-pressure hydrocephalus (NPH). Moreover, aqueductal stenosis (AS) is not always detected by conventional magnetic resonance imaging (MRI). The aim of this study was to compare the hydrodynamic pattern among NPH patients according to the patency of the aqueduct. Fifty-six consecutive lumbar infusion tests were performed in patients with NPH syndrome. Precipitating causes of hydrocephalus were excluded, and aqueductal patency was examined through high-resolution, T2-weighted 3D MRI. Patients were classified into two groups: non-patent aqueduct and patent aqueduct. Mean values of pressure and pulse amplitude were obtained from basal and plateau stages of infusion studies. Twelve of 56 patients with NPH-like symptoms presented with morphological AS (21.4%). Patent aqueduct and non-patent aqueduct groups had similar values of mean opening lumbar pressure (8.2 vs. 8.1mmHg), and mean opening pulse amplitude (3.1 vs. 2.9mmHg). Mean pressure in the plateau stage (28.6 vs. 23.2mmHg), and mean pulse amplitude in the plateau stage (12.5 vs. 10.6mmHg) were higher in the patent aqueduct group. These differences were not statistically significant. Only Rout was significantly higher in the patent aqueduct group (13.6 vs. 10.1mmHg/ml/min). One-third of NPH patients with AS presented Rout >12mmHg/ml/min. No differences in mean pressure or pulse amplitude during basal and plateau epochs of the lumbar infusion test in NPH patients were detected, regardless of aqueductal patency. However, Rout was significantly higher in patients with patent aqueduct.

Effects of long-acting GnRH antagonist, degarelix acetate, on plasma insulin-like peptide 3, testosterone and luteinizing hormone concentrations, and scrotal circumference in male goats

We recently reported that plasma insulin-like peptide 3 (INSL3) concentrations increased soon after endogenous and exogenous stimulations of LH in male goats and bulls. However, the effects of LH suppression on INSL3 secretion are unknown in domestic animals. Here, we examined the effects of a long-acting GnRH antagonist (degarelix acetate; 4 mg/kg) on the secretions of plasma INSL3 and testosterone in two phases, an immediate and a long-term phase in male goats (n = 6; aged, 13–16 months). During the immediate phase, blood was taken at 15-minute intervals for 8 hours on Days −5, 0, and 3. The GnRH antagonist was administered after 2-hour sampling of Day 0. Moreover, a daily blood sample was taken from Day 0 to Day 7, followed by twice a week until 9 weeks and finally at week 10. The scrotal circumference was recorded before treatment and continued biweekly until week 10. Concentrations of LH, INSL3, and testosterone in plasma were determined by EIA and the pulsatile nature of secretion analyzed using pulse XP software. The mean concentrations, pulse frequency (per hour), and pulse amplitude (peak-nadir) of plasma LH and testosterone reduced from pretreatment to posttreatment Day 0 and Day 3 (P < 0.05). A decline in mean concentrations, pulse frequency, and pulse amplitude of INSL3 was exhibited on posttreatment Day 3 compared with pretreatment (P < 0.01). During long-term sampling, a decline (P < 0.01) in plasma testosterone and INSL3 concentrations was observed 1 day after treatment and remained lower until 8.5 weeks after treatment, and thereafter returned to pretreatment levels. A reduction in scrotal circumference was recorded 4 weeks after treatment and remained lower until 10 weeks after treatment (P < 0.05). In conclusion, the acute regulation of INSL3 by LH was confirmed by reduction of plasma INSL3 levels within 3 days after GnRH antagonist treatment in male goats. Although the onset of suppression of testosterone was more rapid than that of INSL3, the low levels persisted for 8.5 weeks for both hormones, and subsequently the concentrations returned to pretreatment levels. A significant reduction in testicular size was also observed. The quick, long-lasting, and transient suppression of testosterone and INSL3 after a single injection implies a potential application of this antagonist in reversible long-term chemical castration in male goats.

The best marker for guiding the clinical management of patients with raised intracranial pressure-the RAP index or the mean pulse amplitude?

Raised intracranial pressure is a common problem in a variety of neurosurgical conditions including traumatic brain injury, hydrocephalus and intracranial haemorrhage. The clinical management of these patients is guided by a variety of haemodynamic, biochemical and clinical factors. However to date there is no single parameter that is used to guide clinical management of patients with raised intracranial pressure (ICP). However, the role of ICP indices, specifically the mean pulse amplitude (AMP) and RAP index [correlation coefficient (R) between AMP amplitude (A) and mean ICP pressure (P); index of compensatory reserve], as an indicator of true ICP has been investigated. Whilst the RAP index has been used both as a descriptor of neurological deterioration in TBI patients and as a way of characterising the compensatory reserve in hydrocephalus, more recent studies have highlighted the limitation of the RAP index due to the influence that baseline effect errors have on the mean ICP, which is used in the calculation of the RAP index. These studies have suggested that the ICP mean pulse amplitude may be a more accurate marker of true intracranial pressure due to the fact that it is uninfluenced by the mean ICP and, therefore, the AMP may be a more reliable marker than the RAP index for guiding the clinical management of patients with raised ICP. Although further investigation needs to be undertaken in order to fully assess the role of ICP indices in guiding the clinical management of patients with raised ICP, the studies undertaken to date provide an insight into the potential role of ICP indices to treat raised ICP proactively rather than reactively and therefore help prevent or minimise secondary brain injury.

Leptin secretory dynamics and associated disordered eating psychopathology across the weight spectrum.

Leptin secretory dynamics across the weight spectrum and their relationship with disordered eating psychopathology have not been studied. Our objective was to compare leptin secretory dynamics in 13 anorexia nervosa (AN), 12 overweight/obese (OB) and 12 normal-weight women using deconvolution analysis. In this cross-sectional study conducted at a tertiary referral center, serum leptin levels were obtained every 20 min from 2000 to 0800 h. Dual energy X-ray absorptiometry was used to measure percent body fat. Disordered eating psychopathology was assessed by the Eating Disorders Examination-Questionnaire (EDE-Q) and the Eating Disorders Inventory-2 (EDI-2). The groups differed for basal leptin secretion (BASAL) (P=0.02). Mean leptin pulse amplitude, pulse mass, total pulsatile secretion (TPS) and area under the curve (AUC) were significantly different between groups before and after adjustment for BASAL (P<0.0001 for all). Leptin AUC correlated strongly with TPS (r=0.97, P<0.0001) and less with BASAL (r=0.35, P=0.03). On multivariate analysis, only TPS was a significant predictor of leptin AUC (P<0.0001). TPS was inversely associated with most EDE-Q and EDI-2 parameters and the associations remained significant for EDE-Q eating concern (P=0.01), and EDI-2 asceticism, ineffectiveness and social insecurity (P<0.05) after adjusting for BASAL. These relationships were not significant when controlled for percent body fat. Secretory dynamics of leptin differ across weight spectrum, with mean pulse amplitude, mean pulse mass and TPS being low in AN and high in OB. Pulsatile, rather than basal secretion, is the major contributor to leptin AUC. Decreased pulsatile leptin is associated with disordered eating psychopathology, possibly reflecting low percent body fat in AN.

Waveform Analysis of Intraspinal Pressure After Traumatic Spinal Cord Injury: An Observational Study (O-64).

Following a traumatic brain injury (TBI), intracranial pressure (ICP) increases, often resulting in secondary brain insults. After a spinal cord injury, here the cord may be swollen, leading to a local increase in intraspinal pressure (ISP). We hypothesised that waveform analysis methodology similar to that used for ICP after TBI may be applicable for the monitoring of patients with spinal cord injury.An initial cohort of 10 patients with spinal cord injury, as presented by the first author at a meeting in Cambridge in May 2012, were included in this observational study. The whole group (18 patients) was recently presented in the context of clinically oriented findings (Werndle et al., Crit Care Med, 42(3):646-655, 2014, PMID: 24231762). Mean pressure, pulse and respiratory waveform were analysed along slow vasogenic waves.Slow, respiratory and pulse components of ISP were characterised in the time and frequency domains. Mean ISP was 22.5 ± 5.1, mean pulse amplitude 1.57 ± 0.97, mean respiratory amplitude 0.65 ± 0.45 and mean magnitude of slow waves (a 20-s to 3-min period) was 3.97 ± 3.1 (all in millimetres of mercury). With increasing mean ISP, the pulse amplitude increased in all cases. This suggests that the ISP signal is of a similar character to ICP recorded after TBI. Therefore, the methods of ICP analysis can be helpful in ISP analysis.