Effect of a lung recruitment maneuver by high-frequency oscillatory ventilation in experimental acute lung injury on organ blood flow in pigs

INTRODUCTION: The objective was to study the effects of a lung recruitment procedure by stepwise increases of mean airway pressure upon organ blood flow and hemodynamics during high-frequency oscillatory ventilation (HFOV) versus pressure-controlled ventilation (PCV) in experimental lung injury. METHODS: Lung damage was induced by repeated lung lavages in seven anesthetized pigs (23-26 kg). In randomized order, HFOV and PCV were performed with a fixed sequence of mean airway pressure increases (20, 25, and 30 mbar every 30 minutes). The transpulmonary pressure, systemic hemodynamics, intracranial pressure, cerebral perfusion pressure, organ blood flow (fluorescent microspheres), arterial and mixed venous blood gases, and calculated pulmonary shunt were determined at each mean airway pressure setting. RESULTS: The transpulmonary pressure increased during lung recruitment (HFOV, from 15 +/- 3 mbar to 22 +/- 2 mbar, P < 0.05; PCV, from 15 +/- 3 mbar to 23 +/- 2 mbar, P < 0.05), and high airway pressures resulted in elevated left ventricular end-diastolic pressure (HFOV, from 3 +/- 1 mmHg to 6 +/- 3 mmHg, P < 0.05; PCV, from 2 +/- 1 mmHg to 7 +/- 3 mmHg, P < 0.05), pulmonary artery occlusion pressure (HFOV, from 12 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 13 +/- 2 mmHg to 15 +/- 2 mmHg, P < 0.05), and intracranial pressure (HFOV, from 14 +/- 2 mmHg to 16 +/- 2 mmHg, P < 0.05; PCV, from 15 +/- 3 mmHg to 17 +/- 2 mmHg, P < 0.05). Simultaneously, the mean arterial pressure (HFOV, from 89 +/- 7 mmHg to 79 +/- 9 mmHg, P < 0.05; PCV, from 91 +/- 8 mmHg to 81 +/- 8 mmHg, P < 0.05), cardiac output (HFOV, from 3.9 +/- 0.4 l/minute to 3.5 +/- 0.3 l/minute, P < 0.05; PCV, from 3.8 +/- 0.6 l/minute to 3.4 +/- 0.3 l/minute, P < 0.05), and stroke volume (HFOV, from 32 +/- 7 ml to 28 +/- 5 ml, P < 0.05; PCV, from 31 +/- 2 ml to 26 +/- 4 ml, P < 0.05) decreased. Blood flows to the heart, brain, kidneys and jejunum were maintained. Oxygenation improved and the pulmonary shunt fraction decreased below 10% (HFOV, P < 0.05; PCV, P < 0.05). We detected no differences between HFOV and PCV at comparable transpulmonary pressures. CONCLUSION: A typical recruitment procedure at the initiation of HFOV improved oxygenation but also decreased systemic hemodynamics at high transpulmonary pressures when no changes of vasoactive drugs and fluid management were performed. Blood flow to the organs was not affected during lung recruitment. These effects were independent of the ventilator mode applied.

Native EEG and treatment effects in neuroleptic-naïve schizophrenic patients: time and frequency domain approaches

Time domain analysis of electroencephalography (EEG) can identify subsecond periods of quasi-stable brain states. These so-called microstates assumingly correspond to basic units of cognition and emotion. On the other hand, Global Field Synchronization (GFS) is a frequency domain measure to estimate functional synchronization of brain processes on a global level for each EEG frequency band [Koenig, T., Lehmann, D., Saito, N., Kuginuki, T., Kinoshita, T., Koukkou, M., 2001. Decreased functional connectivity of EEG theta-frequency activity in first-episode, neuroleptic-naive patients with schizophrenia: preliminary results. Schizophr Res. 50, 55-60.]. Using these time and frequency domain analyzes, several previous studies reported shortened microstate duration in specific microstate classes and decreased GFS in theta band in drug naïve schizophrenia compared to controls. The purpose of this study was to investigate changes of these EEG parameters after drug treatment in drug naïve schizophrenia. EEG analysis was performed in 21 drug-naive patients and 21 healthy controls. 14 patients were reevaluated 2-8 weeks (mean 4.3) after the initiation of drug administration. The results extended findings of treatment effect on brain functions in schizophrenia, and imply that shortened duration of specific microstate classes seems a state marker especially in patients with later neuroleptic responsive, while lower theta GFS seems a state-related phenomenon and that higher gamma GFS is a trait like phenomenon.

Volume dependence of high-frequency respiratory mechanics in healthy adults

Respiratory system input impedance (Zrs) at low to medium frequencies below 100 Hz, and study of its volume dependence, have been used extensively to quantify airway and tissue mechanics. Zrs at high oscillation frequencies including the first antiresonant frequency (far,1) may contain important information about airway mechanics. Changes in high-frequency Zrs with lung volume have not been studied. The volume-dependent behavior of high-frequency Zrs, specifically far,1 and respiratory system resistance at first antiresonance (Rrs(far,1)), was characterized in 16 healthy adults. Zrs was measured with a forced oscillation signal (5-302.5 Hz) through a wavetube setup. To track Zrs, subjects performed slow deep inspiratory and expiratory maneuvers over 30-s measurements, during which average impedance was calculated over 0.4-s intervals, with successive overlapping estimates every 0.156 s. Flow was measured using a pneumotachometer and integrated to obtain volume. Transpulmonary pressure dependence (Ptp) of Zrs was separately determined in five subjects. Both far,1 and Rrs(far,1) decreased with increasing lung volume and Ptp, consistent with an increase in airway caliber and decreased airway wall compliance as volume increased. These characterizations provide insight into airway mechanics, and are furthermore a necessary first step toward determining whether volume dependence of the first antiresonance is altered in disease.

Stability measurements of 1-stage implants in the edentulous mandible by means of resonance frequency analysis

OBJECTIVE: Resonance frequency analysis (RFA) is a method of measuring implant stability. However, little is known about RFA of implants with long loading periods. The objective of the present study was to determine standard implant stability quotients (ISQs) for clinical successfully osseointegrated 1-stage implants in the edentulous mandible. MATERIALS AND METHODS: Stability measurements by means of RFA were performed in regularly followed patients who had received 1- stage implants for overdenture support. The time interval between implant placement and measurement ranged from 1 year up to 10 years. The short-term group comprised patients who were followed up to 5 years, while the long-term group included patients with an observation time of > 5 years up to 10 years. For further comparison RFA measurements were performed in a matching group with unloaded implants at the end of the surgical procedure. For statistical analysis various parameters that might influence the ISQs of loaded implants were included, and a mixed-effects model applied (regression analysis, P <.0125). RESULTS: Ninety-four patients were available with a total of 205 loaded implants, and 16 patients with 36 implants immediately after the surgical procedure. The mean ISQ of all measured implants was 64.5 +/- 7.9 (range, 58 to 72). Statistical analysis did not reveal significant differences in the mean ISQ related to the observation time. The parameters with overall statistical significance were the diameter of the implants and changes in the attachment level. In the short-term group, the gender and the clinically measured attachment level had a significant effect. Implant diameter had a significant effect in the long-term group. CONCLUSIONS: A mean ISQ of 64.5 +/- 7.9 was found to be representative for stable asymptomatic interforaminal implants measured by the RFA instrument at any given time point. No significant differences in ISQ values were found between implants with different postsurgical time intervals. Implant diameter appears to influence the ISQ of interforaminal implants.

Childhood extraordinary daytime urinary frequency-a case series and a systematic literature review

Childhood extraordinary daytime urinary frequency is likely a common but underreported condition characterized by daytime frequent voiding and typically not linked with complaints of burning, urinary incontinence, altered urinary stream, changes in the nighttime voiding pattern, excessive fluid intake and excessive urinary volume. To determine the features and outcome of extraordinary daytime urinary frequency, we report our experience with 14 children and the results of a formal systematic analysis of peer-reviewed English-language literature on this topic. Nineteen case series were found (together with 16 mostly pertinent comments), with each case series providing details on from one to 119 children. On the basis of our experience and the findings of our systematic analysis, we conclude that, in general practice, extraordinary daytime urinary frequency is a common cause of urinary frequency, that the age of such patients is, on average, 6 years and that the micturation abnormalities persist for an average of 6 months. The results of this review must be viewed with an understanding of the limitations of the analysis process, which incorporated data exclusively from case series.

Pregnancy induces numerical and functional changes of CD4+CD25 high regulatory T cells in patients with rheumatoid arthritis

OBJECTIVE: In a prospective study we investigated whether numerical and functional changes of CD4+CD25(high) regulatory T cells (Treg) were associated with changes of disease activity observed during pregnancy and post partum in patients with rheumatoid arthritis (RA). METHODS: The frequency of CD4+CD25(high) T cells was determined by flow cytometry in 12 patients with RA and 14 healthy women during and after pregnancy. Fluorescence-activated cell sorting (FACS) was used to sort CD4+CD25(high) T cells and CD4+CD25- T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies alone or in co-culture to investigate proliferation and cytokine secretion. RESULTS: Frequencies of CD4+CD25(high) Treg were significantly higher in the third trimester compared to 8 weeks post partum in patients and controls. Numbers of CD4+CD25(high) Treg inversely correlated with disease activity in the third trimester and post partum. In co-culture experiments significantly higher amounts of IL10 and lowered levels of tumour necrosis factor (TNF)alpha and interferon (IFN)gamma were found in supernatants of the third trimester compared to postpartum samples. These findings were independent from health or disease in pregnancy, however postpartum TNFalpha and IFN gamma levels were higher in patients with disease flares. CONCLUSION: The amelioration of disease activity in the third trimester corresponded to the increased number of Treg that induced a pronounced anti-inflammatory cytokine milieu. The pregnancy related quantitative and qualitative changes of Treg suggest a beneficial effect of Treg on disease activity.

Lipodystrophy and weight changes: data from the Swiss HIV Cohort Study, 2000-2006

BACKGROUND AND OBJECTIVES: Combination antiretroviral therapy (cART) is changing, and this may affect the type and occurrence of side effects. We examined the frequency of lipodystrophy (LD) and weight changes in relation to the use of specific drugs in the Swiss HIV Cohort Study (SHCS). METHODS: In the SHCS, patients are followed twice a year and scored by the treating physician as having 'fat accumulation', 'fat loss', or neither. Treatments, and reasons for change thereof, are recorded. Our study sample included all patients treated with cART between 2003 and 2006 and, in addition, all patients who started cART between 2000 and 2003. RESULTS: From 2003 to 2006, the percentage of patients taking stavudine, didanosine and nelfinavir decreased, the percentage taking lopinavir, nevirapine and efavirenz remained stable, and the percentage taking atazanavir and tenofovir increased by 18.7 and 22.2%, respectively. In life-table Kaplan-Meier analysis, patients starting cART in 2003-2006 were less likely to develop LD than those starting cART from 2000 to 2002 (P<0.02). LD was quoted as the reason for treatment change or discontinuation for 4% of patients on cART in 2003, and for 1% of patients treated in 2006 (P for trend <0.001). In univariate and multivariate regression analysis, patients with a weight gain of >or=5 kg were more likely to take lopinavir or atazanavir than patients without such a weight gain [odds ratio (OR) 2, 95% confidence interval (CI) 1.3-2.9, and OR 1.7, 95% CI 1.3-2.1, respectively]. CONCLUSIONS: LD has become less frequent in the SHCS from 2000 to 2006. A weight gain of more than 5 kg was associated with the use of atazanavir and lopinavir.

Phenotyping, functional characterization, and developmental changes in canine intestinal intraepithelial lymphocytes

Little is currently known about the lymphocyte populations in the normal and diseased canine gut. The aim of this study was thus the phenotypical and functional characterization of canine intestinal intraepithelial lymphocytes (IEL). IEL were isolated from full-thickness biopsies of 15 adult Swiss Beagle dogs (mean age 8.2 +/-2.8 years) and compared to mesenteric lymph node cells. The phenotypical characterization by multi-parameter flow cytometry revealed that canine IEL differ substantially from lymph node T cells, and consist of various unconventional lymphocyte subsets, unique to mucosal surfaces. These include gammasigma T cells, and CD4(-)CD8(-) and CD8alphaalpha(+) T cells. IEL populations in adult dogs were also compared to those isolated from neonatal Beagle dogs. Analysis revealed a high frequency of undifferentiated CD4(-)CD8(-) T cells in newborn dogs whereas mature CD4(+) and CD8(+) T cells predominate in adult dogs, indicating maturation of the intestinal immune system during development. As IEL in other species are thought to exhibit regulatory functions, we investigated the role of IEL on the activation-induced proliferation of lymph node T cells. While IEL alone did not show activation-induced proliferation, they significantly inhibited the proliferation of activated lymph node T cells in a cell number-dependent manner. These findings are the first to demonstrate that canine intestinal IEL have an immunoregulatory phenotype, which may contribute to the maintenance of intestinal immune homeostasis and may, therefore, be lost in canine chronic enteropathies.

Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis

INTRODUCTION: Recent findings suggest that articular cartilage contains mesenchymal progenitor cells. The aim of this study was to examine the distribution of stem cell markers (Notch-1, Stro-1 and VCAM-1) and of molecules that modulate progenitor differentiation (Notch-1 and Sox9) in normal adult human articular cartilage and in osteoarthritis (OA) cartilage. METHODS: Expression of the markers was analyzed by immunohistochemistry (IHC) and flow cytometry. Hoechst 33342 dye was used to identify and sort the cartilage side population (SP). Multilineage differentiation assays including chondrogenesis, osteogenesis and adipogenesis were performed on SP and non-SP (NSP) cells. RESULTS: A surprisingly high number (>45%) of cells were positive for Notch-1, Stro-1 and VCAM-1 throughout normal cartilage. Expression of these markers was higher in the superficial zone (SZ) of normal cartilage as compared to the middle zone (MZ) and deep zone (DZ). Non-fibrillated OA cartilage SZ showed reduced Notch-1 and Sox9 staining frequency, while Notch-1, Stro-1 and VCAM-1 positive cells were increased in the MZ. Most cells in OA clusters were positive for each molecule tested. The frequency of SP cells in cartilage was 0.14 +/- 0.05% and no difference was found between normal and OA. SP cells displayed chondrogenic and osteogenic but not adipogenic differentiation potential. CONCLUSIONS: These results show a surprisingly high number of cells that express putative progenitor cell markers in human cartilage. In contrast, the percentage of SP cells is much lower and within the range of expected stem cell frequency. Thus, markers such as Notch-1, Stro-1 or VCAM-1 may not be useful to identify progenitors in cartilage. Instead, their increased expression in OA cartilage implicates involvement in the abnormal cell activation and differentiation process characteristic of OA.

Quantifying the influence of bone density and thickness on resonance frequency analysis: an in vitro study of biomechanical test materials

PURPOSE: Resonance frequency analysis (RFA) offers the opportunity to monitor the osseointegration of an implant in a simple, noninvasive way. A better comprehension of the relationship between RFA and parameters related to bone quality would therefore help clinicians improve diagnoses. In this study, a bone analog made from polyurethane foam was used to isolate the influences of bone density and cortical thickness in RFA. MATERIALS AND METHODS: Straumann standard implants were inserted in polyurethane foam blocks, and primary implant stability was measured with RFA. The blocks were composed of two superimposed layers with different densities. The top layer was dense to mimic cortical bone, whereas the bottom layer had a lower density to represent trabecular bone. Different densities for both layers and different thicknesses for the simulated cortical layer were tested, resulting in eight different block combinations. RFA was compared with two other mechanical evaluations of primary stability: removal torque and axial loading response. RESULTS: The primary stability measured with RFA did not correlate with the two other methods, but there was a significant correlation between removal torque and the axial loading response (P < .005). Statistical analysis revealed that each method was sensitive to different aspects of bone quality. RFA was the only method able to detect changes in both bone density and cortical thickness. However, changes in trabecular bone density were easier to distinguish with removal torque and axial loading than with RFA. CONCLUSIONS: This study shows that RFA, removal torque, and axial loading are sensitive to different aspects of the bone-implant interface. This explains the absence of correlation among the methods and proves that no standard procedure exists for the evaluation of primary stability.

Space–oriented EEG segmentation reveals changes in brain electric–field maps under the influence of a nootropic drug

Map landscape-based segmentation of the sequences of momentary potential distribution maps (42-channel recordings) into brain microstates during spontaneous brain activity was used to study brain electric field spatial effects of single doses of piracetam (2.9, 4.8, and 9.6 g Nootropil® UCB and placebo) in a double-blind study of five normal young volunteers. Four 15-second epochs were analyzed from each subject and drug condition. The most prominent class of microstates (covering 49% of the time) consisted of potential maps with a generally anterior-posterior field orientation. The map orientation of this microstate class showed an increasing clockwise deviation from the placebo condition with increasing drug doses (Fisher's probability product, p < 0.014). The results of this study suggest the use of microstate segmentation analysis for the assessment of central effects of medication in spontaneous multichannel electroencephalographic data, as a complementary approach to frequency-domain analysis.

Smell and taste of chewing gum affect frequency domain EEG source localizations

We investigated brain electric field signatures of subjective feelings after chewing regular gum or gum base without flavor. 19-channel eyes-closed EEG from 20 healthy males before and after 5 minutes of chewing the two gum types in random sequence was source modeled in the frequency domain using the FFT-Dipole-Approximation. 3-dimensional brain locations and strengths (Global Field Power, GFP) of the equivalent sources of five frequency bands were computed as changes from pre-chewing baseline. Gum types differed (ANOVA) in pre-post changes of source locations for the alpha-2 band (to anterior and right after regular gum, opposite after gum base) and beta-2 band (to anterior and inferior after regular gum, opposite after gum base), and of GFP for delta-theta, alpha-2 and beta-1 (regular gum: increase, gum base: decrease). Subjective feeling changed to more positive values after regular gum than gum base (ANOVA).—Thus, chewing gum with and without taste-smell activates different brain neuronal populations.

Holocene flood frequency across the Central Alps – solar forcing and evidence for variations in North Atlantic atmospheric circulation

The frequency of large-scale heavy precipitation events in the European Alps is expected to undergo substantial changes with current climate change. Hence, knowledge about the past natural variability of floods caused by heavy precipitation constitutes important input for climate projections. We present a comprehensive Holocene (10,000 years) reconstruction of the flood frequency in the Central European Alps combining 15 lacustrine sediment records. These records provide an extensive catalog of flood deposits, which were generated by flood-induced underflows delivering terrestrial material to the lake floors. The multi-archive approach allows suppressing local weather patterns, such as thunderstorms, from the obtained climate signal. We reconstructed mainly late spring to fall events since ice cover and precipitation in form of snow in winter at high-altitude study sites do inhibit the generation of flood layers. We found that flood frequency was higher during cool periods, coinciding with lows in solar activity. In addition, flood occurrence shows periodicities that are also observed in reconstructions of solar activity from C-14 and Be-10 records (2500-3000, 900-1200, as well as of about 710, 500, 350, 208 (Suess cycle), 150, 104 and 87 (Gleissberg cycle) years). As atmospheric mechanism, we propose an expansion/shrinking of the Hadley cell with increasing/decreasing air temperature, causing dry/wet conditions in Central Europe during phases of high/low solar activity. Furthermore, differences between the flood patterns from the Northern Alps and the Southern Alps indicate changes in North Atlantic circulation. Enhanced flood occurrence in the South compared to the North suggests a pronounced southward position of the Westerlies and/or blocking over the northern North Atlantic, hence resembling a negative NAO state (most distinct from 4.2 to 2.4 kyr BP and during the Little Ice Age). South-Alpine flood activity therefore provides a qualitative record of variations in a paleo-NAO pattern during the Holocene. Additionally, increased South Alpine flood activity contrasts to low precipitation in tropical Central America (Cariaco Basin) on the Holocene and centennial time scale. This observation is consistent with a Holocene southward migration of the Atlantic circulation system, and hence of the ITCZ, driven by decreasing summer insolation in the Northern hemisphere, as well as with shorter-term fluctuations probably driven by solar activity. (C) 2013 Elsevier Ltd. All rights reserved.

Seasonal changes in the behaviour and respiration physiology of the freshwater duck mussel, Anodonta anatina.

For low-energy organisms such as bivalves, the costs of thermal compensation of biological rates (synonymous with acclimation or acclimatization) may be higher than the benefits. We therefore conducted two experiments to examine the effect of seasonal temperature changes on behaviour and oxygen consumption. In the first experiment, we examined the effects of seasonal temperature changes on the freshwater bivalve Anodonta anatina, taking measurements each month for a year at the corresponding temperature for that time of year. There was no evidence for compensation of burrowing valve closure duration or frequency, or locomotory speed. In the second experiment, we compared A. anatina at summer and winter temperatures (24 and 4°C, respectively) and found no evidence for compensation of the burrowing rate, valve closure duration or frequency, or oxygen consumption rates during burrowing, immediately after valve closure or at rest. Within the experimental limits of this study, the evidence suggests that thermal compensation of biological rates is not a strategy employed by A. anatina. We argue that this is due to either a lack of evolutionary pressure to acclimatize, or evolutionary pressure to not acclimatize. Firstly, there is little incentive to increase metabolic rate to enhance predatory ability given that these are filter feeders. Secondly, maintained low energetic demand, enhanced at winter temperatures, is essential for predator avoidance, i.e. valve closure. Thus, we suggest that the costs of acclimatization outweigh the benefits in A. anatina.

End-tidal CO2 pressure: an important parameter for a correct interpretation of changes in cerebral hemodynamics and oxygenation measured with functional near infrared spectrophotometry (fNIRS)

The aim of the present study was to investigate the effects of different speech tasks (recitation of prose (PR), alliteration (AR) and hexameter (HR) verses) and a control task (mental arithmetic (MA) with voicing of the result) on endtidal CO2 (ET-CO2), cerebral hemodynamics; i.e. total hemoglobin (tHb) and tissue oxygen saturation (StO2). tHb and StO2 were measured with a frequency domain near infrared spectrophotometer (ISS Inc., USA) and ET-CO2 with a gas analyzer (Nellcor N1000). Measurements were performed in 24 adult volunteers (11 female, 13 male; age range 22 to 64 years) during task performance in a randomized order on 4 different days to avoid potential carry over effects. Statistical analysis was applied to test differences between baseline, 2 recitation and 5 recovery periods. The two brain hemispheres and 4 tasks were tested separately. Data analysis revealed that during the recitation tasks (PR, AR and HR) StO2 decreased statistically significant (p < 0.05) during PR and AR in the right prefrontal cortex (PFC) and during AR and HR in the left PFC. tHb showed a significant decrease during HR in the right PFC and during PR, AR and HR in the left PFC. During the MA task, StO2 increased significantly. A significant decrease in ET-CO2 was found during all 4 tasks with the smallest decrease during the MA task. In conclusion, we hypothesize that the observed changes in tHb and StO2 are mainly caused by an altered breathing during the tasks that led a lowering of the CO2 content in the blood provoked a cerebral CO2 reaction, i.e. a vasoconstriction of blood vessels due to decreased CO2 pressure and thereby decrease in cerebral blood volume. Therefore, breathing changes should be monitored during brain studies involving speech when using functional near infrared spectroscopy (fNIRS) to ensure a correct interpretation of changes in hemodynamics and oxygenation.