Dilution and redistribution effects of rapid 2-litre infusions of 0.9% (w/v) saline and 5% (w/v) dextrose on haematological parameters and serum biochemistry in normal subjects: a double-blind crossover study

Although hypoalbuminaemia after injury may result from increased vascular permeability, dilution secondary to crystalloid infusions may contribute significantly. In this double-blind crossover study, the effects of bolus infusions of crystalloids on serum albumin, haematocrit, serum and urinary biochemistry and bioelectrical impedance analysis were measured in healthy subjects. Ten male volunteers received 2-litre infusions of 0.9% (w/v) saline or 5% (w/v) dextrose over 1 h; infusions were carried out on separate occasions, in random order. Weight, haemoglobin, serum albumin, serum and urinary biochemistry and bioelectrical impedance were measured pre-infusion and hourly for 6 h. The serum albumin concentration fell in all subjects (20% after saline; 16% after dextrose) by more than could be explained by dilution alone. This fall lasted more than 6 h after saline infusion, but values had returned to baseline 1 h after the end of the dextrose infusion. Changes in haematocrit and haemoglobin were less pronounced (7.5% after saline; 6.5% after dextrose). Whereas all the water from dextrose was excreted by 2 h after completion of the infusion, only one-third of the sodium and water from the saline had been excreted by 6 h, explaining its persistent diluting effect. Impedances rose after dextrose and fell after saline (P<0.001). Subjects voided more urine (means 1663 and 563 ml respectively) of lower osmolality (means 129 and 630 mOsm/kg respectively) and sodium content (means 26 and 95 mmol respectively) after dextrose than after saline (P<0.001). While an excess water load is excreted rapidly, an excess sodium load is excreted very slowly, even in normal subjects, and causes persistent dilution of haematocrit and serum albumin. The greater than expected change in serum albumin concentration when compared with that of haemoglobin suggests that, while dilution is responsible for the latter, redistribution also has a role in the former. Changes in bioelectrical impedance may reflect the electrolyte content rather than the volume of the infusate, and may be unreliable for clinical purposes.

Brain electrical microstates in subjects with panic disorder

Brain electrical microstates represent spatial configurations of scalp recorded brain electrical activity and are considered to be the basic elements of stepwise processing of information in the brain. In the present study, the hypothesis of a temporo-limbic dysfunction in panic disorder (PD) was tested by investigating the topographic descriptors of brain microstates, in particular the one corresponding to the Late Positive Complex (LPC), an event-related potential (ERP) component with generators in these regions. ERPs were recorded in PD patients and matched healthy subjects during a target detection task, in a central (CC) and a lateral condition (LC). In the CC, a leftward shift of the LPC microstate positive centroid was observed in the patients with PD versus the healthy control subjects. In the LC, the topographic descriptor of the first microstate showed a rightward shift, while those of both the second and the fourth microstate, corresponding to the LPC, revealed a leftward shift in the PD patients versus the healthy control subjects. These findings indicate an overactivation of the right hemisphere networks involved in early visual processing and a hypoactivation of the right hemisphere circuits involved in LPC generators in PD. In line with this interpretation, the abnormal topography of the LPC microstate, observed in the CC, was associated with a worse performance on a test exploring right temporo-hippocampal functioning. Topographical abnormalities found for the LPC microstate in the LC were associated with a higher number of panic attacks, suggesting a pathogenetic role of the right temporo-hippocampal dysfunction in PD.

Hemispheric lateralization patterns and psychotic experiences in healthy subjects

The hypothesis that psychotic experiences in healthy subjects are associated with a dysfunction of the right hemisphere is supported by some, but not all, available studies. Differences in gender composition of study samples may explain in part the divergent findings. The present study was carried out in 42 healthy, right-handed university students. Scores on the Schizophrenia and Paranoia scales of the Minnesota Multidimensional Personality Inventory-2 were used in correlation analyses and to define a High- and a Low-Psychotic group. Brain Electrical Microstates and Low Resolution Electromagnetic Tomography (LORETA) source analyses of the auditory P300 (P3a and P3b) components of the event-related potential, as well as a battery of neuropsychological tests, were used to assess hemispheric functioning. Scores on the Paranoia scale were positively associated with a leftward shift of the P3a topographic descriptors in females but not in males. When comparing High-Psychotic and Low-Psychotic females, a leftward shift of P3a descriptors and an increased cortical activation in left fronto-temporal areas were observed in the High-Psychotic group. Our results demonstrated gender-related differences in the pattern of hemispheric imbalance associated with psychotic experiences in healthy subjects.

Gingival labial recessions in orthodontically treated and untreated individuals: a case - control study

OBJECTIVES To evaluate the long-term development of labial gingival recessions during orthodontic treatment and retention phase. MATERIAL AND METHODS In this retrospective case-control study, the presence of gingival recession was scored (Yes or No) on plaster models of 100 orthodontic patients (cases) and 120 controls at the age of 12 (T12 ), 15 (T15 ), 18 (T18 ), and 21 (T21 ) years. In the treated group, T12 reflected the start of orthodontic treatment and T15 - the end of active treatment and the start of retention phase with bonded retainers. Independent t-tests, Fisher's exact tests and a fitted two-part "hurdle" model were used to identify the effect of orthodontic treatment/retention on recessions. RESULTS The proportion of subjects with recessions was consistently higher in cases than controls. Overall, the odds ratio for orthodontic patients as compared with controls to have recessions is 4.48 (p < 0.001; 95% CI: 2.61-7.70). CONCLUSIONS Within the limits of the present research design, orthodontic treatment and/or the retention phase may be risk factors for the development of labial gingival recessions. In orthodontically treated subjects, mandibular incisors seem to be the most vulnerable to the development of gingival recessions.

Comfort of two shoulder actuation mechanisms for arm therapy exoskeletons: a comparative study in healthy subjects

Robotic exoskeletons can be used to study and treat patients with neurological impairments. They can guide and support the human limb over a large range of motion, which requires that the movement trajectory of the exoskeleton coincide with the one of the human arm. This is straightforward to achieve for rather simple joints like the elbow, but very challenging for complex joints like the human shoulder, which is comprised by several bones and can exhibit a movement with multiple rotational and translational degrees of freedom. Thus, several research groups have developed different shoulder actuation mechanism. However, there are no experimental studies that directly compare the comfort of two different shoulder actuation mechanisms. In this study, the comfort and the naturalness of the new shoulder actuation mechanism of the ARMin III exoskeleton are compared to a ball-and-socket-type shoulder actuation. The study was conducted in 20 healthy subjects using questionnaires and 3D-motion records to assess comfort and naturalness. The results indicate that the new shoulder actuation is slightly better than a ball-and-socket-type actuation. However, the differences are small, and under the tested conditions, the comfort and the naturalness of the two tested shoulder actuations do not differ a lot.

Hemispheric asymmetry in visuospatial attention assessed with transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) was used to study visuospatial attention processing in ten healthy volunteers. In a forced choice recognition task the subjects were confronted with two symbols simultaneously presented during 120 ms at random positions, one in the left and the other in the right visual field. The subject had to identify the presented pattern out of four possible combinations and to press the corresponding response key within 2 s. Double-pulse TMS (dTMS) with a 100-ms interstimulus interval (ISI) and an intensity of 80% of the stimulator output (corresponding to 110-120% of the motor threshold) was applied by a non-focal coil over the right or left posterior parietal cortex (PPC, corresponding to P3/P4 of the international 10-20 system) at different time intervals after onset of the visual stimulus (starting at 120 ms, 270 ms and 520 ms). Double-pulse TMS over the right PPC starting at 270 ms led to a significant increase in percentage of errors in the contralateral, left visual field (median: 23% with TMS vs 13% without TMS, P=0.0025). TMS applied earlier or later showed no effect. Furthermore, no significant increase in contra- or ipsilateral percentage of errors was found when the left parietal cortex was stimulated with the same timing. These data indicate that: (1) parietal influence on visuospatial attention is mainly controlled by the right lobe since the same stimulation over the left parietal cortex had no significant effect, and (2) there is a vulnerable time window to disturb this cortical process, since dTMS had a significant effect on the percentage of errors in the contralateral visual hemifield only when applied 270 ms after visual stimulus presentation.

Quantification of Popliteal Artery Deformation During Leg Flexion in Subjects With Peripheral Artery Disease: A Pilot Study

Purpose: To quantify the in vivo deformations of the popliteal artery during leg flexion in subjects with clinically relevant peripheral artery disease (PAD). Methods: Five patients (4 men; mean age 69 years, range 56–79) with varying calcification levels of the popliteal artery undergoing endovascular revascularization underwent 3-dimensional (3D) rotational angiography. Image acquisition was performed with the leg straight and with a flexion of 70°/20° in the knee/hip joints. The arterial centerline and the corresponding branches in both positions were segmented to create 3D reconstructions of the arterial trees. Axial deformation, twisting, and curvatures were quantified. Furthermore, the relationships between the calcification levels and the deformations were investigated. Results: An average shortening of 5.9%±2.5% and twist rate of 3.8±2.2°/cm in the popliteal artery were observed. Maximal curvatures in the straight and flexed positions were 0.12±0.04 cm−1 and 0.24±0.09 cm−1, respectively. As the severity of calcification increased, the maximal curvature in the straight position increased from 0.08 to 0.17 cm−1, while an increase from 0.17 to 0.39 cm−1 was observed for the flexed position. Axial elongations and arterial twisting were not affected by the calcification levels. Conclusion: The popliteal artery of patients with symptomatic PAD is exposed to significant deformations during flexion of the knee joint. The severity of calcification directly affects curvature, but not arterial length or twisting angles. This pilot study also showed the ability of rotational angiography to quantify the 3D deformations of the popliteal artery in patients with various levels of calcification.

The effect of aerobic exercise on intrahepatocellular and intramyocellular lipids in healthy subjects

BACKGROUND Intrahepatocellular (IHCL) and intramyocellular (IMCL) lipids are ectopic lipid stores. Aerobic exercise results in IMCL utilization in subjects over a broad range of exercise capacity. IMCL and IHCL have been related to impaired insulin action at the skeletal muscle and hepatic level, respectively. The acute effect of aerobic exercise on IHCL is unknown. Possible regulatory factors include exercise capacity, insulin sensitivity and fat availability subcutaneous and visceral fat mass). AIM To concomitantly investigate the effect of aerobic exercise on IHCL and IMCL in healthy subjects, using Magnetic Resonance spectroscopy. METHODS Normal weight, healthy subjects were included. Visit 1 consisted of a determination of VO2max on a treadmill. Visit 2 comprised the assessment of hepatic and peripheral insulin sensitivity by a two-step hyperinsulinaemic euglycaemic clamp. At Visit 3, subcutaneous and visceral fat mass were assessed by whole body MRI, IHCL and IMCL before and after a 2-hours aerobic exercise (50% of VO(2max)) using ¹H-MR-spectroscopy. RESULTS Eighteen volunteers (12M, 6F) were enrolled in the study (age, 37.6±3.2 years, mean±SEM; VO(2max), 53.4±2.9 mL/kg/min). Two hours aerobic exercise resulted in a significant decrease in IMCL (-22.6±3.3, % from baseline) and increase in IHCL (+34.9±7.6, % from baseline). There was no significant correlation between the exercise-induced changes in IMCL and IHCL and exercise capacity, subcutaneous and visceral fat mass and hepatic or peripheral insulin sensitivity. CONCLUSIONS IMCL and IHCL are flexible ectopic lipid stores that are acutely influenced by physical exercise, albeit in different directions. TRIAL REGISTRATION ClinicalTrial.gov NCT00491582.

Growth hormone response to catecholamine depletion in unmedicated, remitted subjects with major depressive disorder and healthy controls

We investigated whether the human growth hormone (HGH) response to catecholamine depletion differs between fully remitted patients with major depressive disorder and healthy control subjects. Fourteen unmedicated subjects with remitted major depressive disorder (RMDD) and 11 healthy control subjects underwent catecholamine depletion with oral α-methylparatyrosine (AMPT) in a randomized, placebo-controlled, double-blind crossover study. The main outcome measure was the serum level of HGH. The diagnosis × drug interaction for HGH serum concentration was significant (F₁,₂₃ = 7.66, P < 0.02). This interaction was attributable to the HGH level increasing after AMPT administration in the RMDD subjects but not in the healthy subjects. In the RMDD sample, the AMPT-induced increase in HGH concentration correlated inversely with AMPT-induced anxiety symptoms as assessed using the Beck Anxiety Inventory (r = -0.63, P < 0.02). There was a trend toward an inverse correlation of the AMPT-induced HGH concentration changes with AMPT-induced depressive symptoms as measured by the BDI (r = -0.53, P = 0.05). Following catecholamine depletion, the RMDD subjects were differentiated from control subjects by their HGH responses. This finding, together with the negative correlation between HGH response and AMPT-induced anxiety symptoms in RMDD subjects, suggests that AMPT administration results in a deeper nadir in central catecholaminergic transmission, as reflected by a greater disinhibition of HGH secretion, in RMDD subjects versus control subjects.

Fear-learning deficits in subjects with fibromyalgia syndrome?

BACKGROUND: Fibromyalgia syndrome (FMS) is frequently associated with psychiatric conditions, particularly anxiety. Deficits in contingency learning during fear conditioning have been hypothesized to increase anxiety and, consequently, pain sensation in susceptible individuals. The goal of this study was to examine the relationship between contingency learning and pain experience in subjects with FMS and rheumatoid arthritis (RA). METHODS: Fourteen female FMS subjects, 14 age-matched female RA subjects and 14 age-matched female healthy controls (HCs) were included in a fear-conditioning experiment. The conditioned stimulus (CS) consisted of visual signs, the unconditioned stimulus (US) of thermal stimuli. CS- predicted low-temperature exposure (US), while CS+ was followed by low or high temperature. RESULTS: In the FMS group, only 50% of the subjects were aware of the US-CS contingency, whereas 86% of the RA subjects and all of the HCs were aware of the contingency. CS+ induced more anxiety than CS- in RA subjects and HCs. As expected, low-temperature exposure was experienced as less painful after CS- than after CS+ in these subjects. FMS subjects did not show such adaptive conditioning. The effects of the type of CS on heart rate changes were significant in the HCs and the aware FMS subjects, but not in the unaware FMS subjects. CONCLUSIONS: Contingency learning deficits represent a potentially promising and specific, but largely unstudied, psychopathological factor in FMS. Deficits in contingency learning may increase anxiety and, consequently, pain sensation. These findings have the potential to contribute to the development of novel therapeutic approaches for FMS.

Behavioral responses to catecholamine depletion in unmedicated, remitted subjects with bulimia nervosa and healthy subjects

BACKGROUND: Bulimia nervosa (BN) has been associated with dysregulation of the central catecholaminergic system. An instructive way to investigate the relationship between catecholaminergic function and psychiatric disorder has involved behavioral responses to experimental catecholamine depletion (CD). The purpose of this study was to examine a possible catecholaminergic dysfunction in the pathogenesis of bulimia nervosa. METHODS: CD was achieved by oral administration of alpha-methyl-para-tyrosine (AMPT) in 18 remitted female subjects with BN (rBN) and 31 healthy female control subjects. The study design consisted of a randomized, double blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were bulimic symptoms assessed by the Eating Disorder Examination-Questionnaire. Measures were assessed before and 26, 30, 54, 78, 102 hours after the first AMPT or placebo administration. RESULTS: In the experimental environment (controlled environment with a low level of food cues) rBN subjects had a greater increase in eating disorder symptoms during CD compared with healthy control subjects (condition × diagnosis interaction, p < .05). In the experimental environment, rBN subjects experienced fewer bulimic symptoms than in the natural environment (uncontrolled environment concerning food cues) 36 hours after the first AMPT intake (environment × diagnosis interaction, p < .05). Serum prolactin levels increased significantly, and to a comparable degree across groups, after AMPT administration. CONCLUSIONS: This study suggests that rBN is associated with vulnerability for developing eating disorder symptoms in response to reduced catecholamine neurotransmission after CD. The findings support the notion of catecholaminergic dysfunction as a possible trait abnormality in BN.

Neural correlates of free T3 alteration after catecholamine depletion in subjects with remitted major depressive disorder and in controls.

RATIONALE: Thyroid hormones and their interactions with catecholamines play a potentially important role in alterations of mood and cognition. OBJECTIVES: This study aimed to examine the neurobiological effects of catecholamine depletion on thyroid hormones by measuring endocrine and cerebral metabolic function in unmedicated subjects with remitted major depressive disorder (RMDD) and in healthy controls. METHODS: This was a randomized, placebo-controlled, and double-blind crossover trial that included 15 unmedicated RMDD subjects and 13 healthy control subjects. The participants underwent two 3-day-long sessions at 1-week intervals; each participant was randomly administered oral α-methyl-para-tyrosine in one session (catecholamine depletion) and an identical capsule containing hydrous lactose (sham depletion) in the other session prior to a [(18)F]-fluorodeoxyglucose positron emission tomography scan. RESULTS: Serum concentrations of free T3 (FT3), free T4 (FT4), and TSH were obtained and assessed with respect to their relationship to regional cerebral glucose metabolism. Both serum FT3 (P = 0.002) and FT4 (P = 0.0009) levels were less suppressed after catecholamine depletion compared with placebo treatment in the entire study sample. There was a positive association between both FT3 (P = 0.0005) and FT4 (P = 0.002) and depressive symptoms measured using the Montgomery-Åsberg Depression Rating Scale. The relative elevation in FT3 level was correlated with a decrease in regional glucose metabolism in the right dorsolateral prefrontal cortex (rDLPFC; P < 0.05, corrected). CONCLUSIONS: This study provided evidence of an association between a thyroid-catecholamine interaction and mood regulation in the rDLPFC.

Can quantitative EEG measures predict clinical outcome in subjects at Clinical High Risk for psychosis? A prospective multicenter study

BACKGROUND Prediction studies in subjects at Clinical High Risk (CHR) for psychosis are hampered by a high proportion of uncertain outcomes. We therefore investigated whether quantitative EEG (QEEG) parameters can contribute to an improved identification of CHR subjects with a later conversion to psychosis. METHODS This investigation was a project within the European Prediction of Psychosis Study (EPOS), a prospective multicenter, naturalistic field study with an 18-month follow-up period. QEEG spectral power and alpha peak frequencies (APF) were determined in 113 CHR subjects. The primary outcome measure was conversion to psychosis. RESULTS Cox regression yielded a model including frontal theta (HR=1.82; [95% CI 1.00-3.32]) and delta (HR=2.60; [95% CI 1.30-5.20]) power, and occipital-parietal APF (HR=.52; [95% CI .35-.80]) as predictors of conversion to psychosis. The resulting equation enabled the development of a prognostic index with three risk classes (hazard rate 0.057 to 0.81). CONCLUSIONS Power in theta and delta ranges and APF contribute to the short-term prediction of psychosis and enable a further stratification of risk in CHR samples. Combined with (other) clinical ratings, EEG parameters may therefore be a useful tool for individualized risk estimation and, consequently, targeted prevention.

Pathways to care in subjects at high risk for psychotic disorders — A European perspective

Evidence-based decisions on indicated prevention in early psychosis require large-scale studies on the pathways to care in high-risk subjects. EPOS (The European Prediction of Psychosis Study), a prospective multi-center, naturalistic field study in four European countries (Finland, Germany, The Netherlands and England), was designed to acquire accurate knowledge about pathways to care and delay in obtaining specialized high risk care. Our high risk sample (n=233) reported on average 2.9 help-seeking contacts, with an average delay between onset of relevant problems to initial help-seeking contact of 72.6 weeks, and between initial help-seeking contact and reaching specialized high risk care of 110.9 weeks. This resulted in a total estimated duration of an unrecognized risk for psychosis of 3 ½ years. Across EPOS EU regions, about 90% of care pathway contacts were within professional health care sectors. Between EPOS regions, differences in the pathways parameters including early detection and health-care systems were often very pronounced. High-risk participants who later made transition to a full psychotic disorder had significantly longer delays between initial help-seeking and receiving appropriate interventions. Our study underlines the need for regionally adapted implementation of early detection and intervention programs within respective mental health and health care networks, including enhancing public awareness of early psychosis.

Quantitative analysis of fluorescence lifetime measurements of the macula using the fluorescence lifetime imaging ophthalmoscope in healthy subjects.

PURPOSE Fundus autofluorescence (FAF) cannot only be characterized by the intensity or the emission spectrum, but also by its lifetime. As the lifetime of a fluorescent molecule is sensitive to its local microenvironment, this technique may provide more information than fundus autofluorescence imaging. We report here the characteristics and repeatability of FAF lifetime measurements of the human macula using a new fluorescence lifetime imaging ophthalmoscope (FLIO). METHODS A total of 31 healthy phakic subjects were included in this study with an age range from 22 to 61 years. For image acquisition, a fluorescence lifetime ophthalmoscope based on a Heidelberg Engineering Spectralis system was used. Fluorescence lifetime maps of the retina were recorded in a short- (498-560 nm) and a long- (560-720 nm) spectral channel. For quantification of fluorescence lifetimes a standard ETDRS grid was used. RESULTS Mean fluorescence lifetimes were shortest in the fovea, with 208 picoseconds for the short-spectral channel and 239 picoseconds for the long-spectral channel, respectively. Fluorescence lifetimes increased from the central area to the outer ring of the ETDRS grid. The test-retest reliability of FLIO was very high for all ETDRS areas (Spearman's ρ = 0.80 for the short- and 0.97 for the long-spectral channel, P < 0.0001). Fluorescence lifetimes increased with age. CONCLUSIONS The FLIO allows reproducible measurements of fluorescence lifetimes of the macula in healthy subjects. By using a custom-built software, we were able to quantify fluorescence lifetimes within the ETDRS grid. Establishing a clinically accessible standard against which to measure FAF lifetimes within the retina is a prerequisite for future studies in retinal disease.