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1.
Pediatr Obes ; 12 Suppl 1: 102-110, 2017 08.
Article in English | MEDLINE | ID: mdl-28752657

ABSTRACT

BACKGROUND: There is limited research in young infants, particularly <3 months of age, on maternal feeding practices in spite of increasing evidence that early weight gain velocity is a determinant of later obesity risk. OBJECTIVE: To examine associations between maternal executive function (cognitive control over one's own behaviour), maternal feeding decisions and infant weight and adiposity gains. METHODS: We used a checklist to assess cues mothers use to decide when to initiate and terminate infant feedings at 2 weeks and 3 months of age (N = 69). Maternal executive function was assessed using the NIH Toolbox Cognition Battery subtests for executive function and infant body composition using air displacement plethysmography. RESULTS: Mothers with higher executive function reported relying on fewer non-satiety cues at 2 weeks of age (ß = -0.29, p = 0.037) and on more infant hunger cues at 3 months of age (ß = 0.31, p = 0.018) in their decisions on initiating and terminating feedings. Responsive feeding decisions, specifically the use of infant-based hunger cues at 3 months, in turn were associated with lower gains in weight-for-length (ß = -0.30, p = 0.028) and percent body fat (ß = -0.2, p = 0.091; non-covariate adjusted ß = -0.27, p = 0.029). CONCLUSIONS: These findings show both an association between maternal executive function and responsive feeding decisions and an association between responsive feeding decisions and infant weight and adiposity gains. The causal nature and direction of these associations require further investigation.


Subject(s)
Adiposity/physiology , Child Development/physiology , Executive Function/physiology , Feeding Behavior/physiology , Weight Gain/physiology , Adult , Body Composition , Body Weight , Breast Feeding , Cues , Female , Humans , Infant , Male , Mothers , Plethysmography
2.
J Breath Res ; 11(2): 026008, 2017 06 12.
Article in English | MEDLINE | ID: mdl-28492183

ABSTRACT

Gastric emptying can be assessed by an oral administration of a 13C labeled substrate and its response in the expiratory release of the oxidation product [Formula: see text]. Impaired gut function, reflected, for example, in an intolerance against enteral nutrition may delay or discontinue gastric emptying, potentially leading to multiple peaks in the time profile of expiration. The resulting profile cannot be analyzed by the usual data evaluation that is based on a 'beta exponential' (BEX) function. We developed a new approach that better reflects the underlying physiology. It allows a flexible time profile of gastric release and considers a transient [Formula: see text] retention in different compartments as well as an incomplete recovery of [Formula: see text] in the expiration. Parameters that describe the distribution/retention kinetics cannot be determined based on the same breath data that were used to estimate emptying. To enable the determination of the kinetic parameters, they were constrained to match published data using a Bayesian statistical analysis. The applicability of the new model was compared with BEX for healthy subjects. BEX fails to explain the observed data and, compared to the new approach, overestimates the speed of emptying. Predictive accuracy under impaired gastric motility was explored using synthetic data. Only the new approach can reproduce a multiphase absorption profile. When routine benchtop equipment was used for measurements, then the rate-limiting step for precision in the estimate of emptying is the quality in the a priori estimate for kinetic parameters rather than precision in measurements. Only about 80% of the absorbed [Formula: see text] has to be released by expiration. With these features, the new approach promises to widen the applicability of breath tests for gastric emptying.


Subject(s)
Breath Tests/methods , Carbon Dioxide/analysis , Gastric Emptying/physiology , Stomach/physiopathology , Administration, Oral , Adult , Bayes Theorem , Carbon Isotopes , Computer Simulation , Exhalation , Female , Humans , Intestinal Absorption , Kinetics , Male , Middle Aged , Uncertainty
3.
J Thromb Haemost ; 15(3): 565-574, 2017 03.
Article in English | MEDLINE | ID: mdl-28005311

ABSTRACT

Essentials Potential neurodevelopmental side effects of thrombopoietin mimetics need to be considered. The effects of eltrombopag (ELT) on neuronal iron status and dendrite development were assessed. ELT crosses the blood-brain barrier and causes iron deficiency in developing neurons. ELT blunts dendrite maturation, indicating a need for more safety studies before neonatal use. SUMMARY: Background Thrombocytopenia is common in sick neonates. Thrombopoietin mimetics (e.g. eltrombopag [ELT]) might provide an alternative therapy for selected neonates with severe and prolonged thrombocytopenia, and for infants and young children with different varieties of thrombocytopenia. However, ELT chelates intracellular iron, which may adversely affect developing organs with high metabolic requirements. Iron deficiency (ID) is particularly deleterious during brain development, impairing neuronal myelination, dopamine signaling and dendritic maturation and ultimately impairing long-term neurological function (e.g. hippocampal-dependent learning and memory). Objective To determine whether ELT crosses the blood-brain barrier (BBB), causes neuronal ID and impairs hippocampal neuron dendrite maturation. Methods ELT transport across the BBB was assessed using primary bovine brain microvascular endothelial cells. Embryonic mouse primary hippocampal neuron cultures were treated with ELT or deferoxamine (DFO, an iron chelator) from 7 days in vitro (DIV) through 14 DIV and assessed for gene expression and neuronal dendrite complexity. Results ELT crossed the BBB in a time-dependent manner. 2 and 6 µm ELT increased Tfr1 and Slc11a2 (iron-responsive genes involved in neuronal iron uptake) mRNA levels, indicating neuronal ID. 6 µm ELT, but not 2 µm ELT, decreased BdnfVI, Camk2a and Vamp1 mRNA levels, suggesting impaired neuronal development and synaptic function. Dendrite branch number and length were reduced in 6 µm ELT-treated neurons, resulting in blunted dendritic arbor complexity that was similar to DFO-treated neurons. Conclusions Eltrombopag treatment during development may impair neuronal structure as a result of neuronal ID. Preclinical in vivo studies are warranted to assess ELT safety during periods of rapid brain development.


Subject(s)
Benzoates/pharmacokinetics , Blood-Brain Barrier/drug effects , Dendrites/drug effects , Hippocampus/drug effects , Hydrazines/pharmacokinetics , Iron/chemistry , Neurons/drug effects , Pyrazoles/pharmacokinetics , Anemia, Iron-Deficiency/physiopathology , Animals , Benzoates/chemistry , Biological Transport , Biomimetics , Cattle , Chelating Agents/chemistry , Chelating Agents/pharmacokinetics , Deferoxamine/pharmacology , Dendrites/metabolism , Green Fluorescent Proteins/metabolism , Hippocampus/metabolism , Hydrazines/chemistry , Mice , Microcirculation , Neuroglia/metabolism , Neurons/metabolism , Pyrazoles/chemistry , Thrombocytopenia/physiopathology , Thrombopoietin
4.
Unfallchirurg ; 120(3): 229-236, 2017 Mar.
Article in German | MEDLINE | ID: mdl-26643362

ABSTRACT

BACKGROUNDS AND OBJECTIVES: As part of the expansion of the site-specific education profile of the medical curriculum MED@ULM of the University of Ulm, a new track "trauma care and trauma research" was established in the winter semester 2012/2013. The acceptance of the track was evaluated during the winter semester 2013/2014. MATERIAL AND METHODS: The 6-semester track extends the existing curriculum by offering subjects in trauma management and trauma research to students of human medicine. A central aim of the track is to promote medical professional competence, expertise in emergency care and competence in trauma-related scientific work and research. Central learning contents could be intensified in newly established emergency simulation training. Additionally, participating students have to perform a doctoral thesis on an obligatory trauma-related experimental subject. A first analysis study focusing on the learning style of the participating students (n = 17) and a control group consisting of members of the same semester (n = 20) was performed using the Kolb learning style inventory. In a validated evaluation in the winter semesters 2013/2014 and 2014/2015, the students were asked about their expectations and experience with the track, criticisms, suggestions and satisfaction with the study conditions. The data were analyzed using descriptive statistics. RESULTS: The analysis of the students' preferred learning styles revealed no differences between track students and the control group. Most of the students considered the track as a form of personal further education. The students had high expectations of practical skills with relevance to the clinical daily routine, learning scientific methods and preparing their thesis. The track students were more critical with regard to the study conditions than the control group students, although the track students of the third semester still judged their studies to be more interesting than the track students of the first semester and the control group. CONCLUSION: With the introduction of the new trauma track into the curriculum of the medical curriculum MED@ULM of the University of Ulm, a further possibility for medical students to focus on their own individual options was established. At least half of the track students wanted to be later active in the triad of patient care, teaching and research. Further investigations are necessary to determine whether the establishment of the trauma track has a positive influence on the number of new recruits in trauma surgery and anesthesiology.


Subject(s)
Biomedical Research/organization & administration , Curriculum , Education, Medical, Graduate/organization & administration , Educational Measurement , Models, Educational , Traumatology/education , Germany , Models, Organizational , Teaching/organization & administration
5.
Emerg Med J ; 32(5): 409-11, 2015 May.
Article in English | MEDLINE | ID: mdl-25714107

ABSTRACT

OBJECTIVE: The increasing prevalence of multidrug resistant bacteria is a problem in the inpatient care setting, and in the emergency care system. The aim of this observational, cross-sectional study was to evaluate the prevalence of pathogens on well-defined surfaces in German ambulances that have been designated as 'ready for service'. METHODS: After informed consent was obtained, ambulance surfaces were sampled with agar plates for microbiological examination during an unannounced visit. A standardised questionnaire was used to obtain information regarding the disinfection protocols used at each rescue station. RESULTS: Methicillin resistant staphylococcus aureus contamination was present in 18 sampling surfaces from 11 out of 150 ambulance vehicles (7%) that were designated as ready for service. Contact surfaces directly surrounding patients or staff were most frequently contaminated with pathogens. However, bacterial contamination was not related to annual missions, methods or frequency of disinfection. CONCLUSIONS: In accordance with previous studies, disinfection and cleaning of areas with direct contact to patients or staff seem to be the most challenging. This should also be reflected in disinfection guidelines and the related continuing education.


Subject(s)
Ambulances , Bacteria/isolation & purification , Fungi/isolation & purification , Agar , Cross Infection/prevention & control , Cross-Sectional Studies , Culture Media , Equipment Contamination , Humans , Prevalence
6.
Nitric Oxide ; 41: 79-84, 2014 Sep 15.
Article in English | MEDLINE | ID: mdl-24963794

ABSTRACT

Our aim was to study the ability of an immortalized cell line (AMJ2-C11) to sustain aerobic cell respiration at decreasing oxygen concentrations under continuous sulfide exposure. We assumed that the rate of elimination of sulfide through the pathway linked to the mitochondrial respiratory chain and therefore operating under aerobic conditions, should decrease with limiting oxygen concentrations. Thus, sulfide's inhibition of cellular respiration would occur faster under continuous sulfide exposure when the oxygen concentration is in the very low range. The experiments were performed with an O2K-oxygraph (Oroboros Instruments) by suspending 0.5-1×10(6) cells in 2 ml of continuously stirred respiration medium at 37 °C and calculating the oxygen flux (JO2) as the negative derivative of the oxygen concentration in the medium. The cells were studied in two different metabolic states, namely under normal physiologic respiration (1) and after uncoupling of mitochondrial respiration (2). Oxygen concentration was controlled by means of a titration-injection pump, resulting in average concentration values of 0.73±0.05 µM, 3.1±0.2 µM, and 6.2±0.2 µM. Simultaneously we injected a 2 mM Na2S solution at a continuous rate of 10 µl/s in order to quantify the titration-time required to reduce the JO2 to 50% of the initial respiratory activity. Under the lowest oxygen concentration this effect was achieved after 3.5 [0.3;3.5] and 11.7 [6.2;21.2]min in the uncoupled and coupled state, respectively. This time was statistically significantly shorter when compared to the intermediate and the highest O2 concentrations tested, which yielded values of 24.6 [15.5;28.1]min (coupled) and 35.9 [27.4;59.2]min (uncoupled), as well as 42.4 [27.5;42.4]min (coupled) and 51.5 [46.4;51.7]min (uncoupled). All data are medians [25%, and 75% percentiles]. Our results confirm that the onset of inhibition of cell respiration by sulfide occurs earlier under a continuous exposure when approaching the anoxic condition. This property may contribute to the physiological role of sulfide as an oxygen sensor.


Subject(s)
Cell Hypoxia/physiology , Oxygen/metabolism , Sulfides/metabolism , Animals , Cell Line , Cell Respiration/physiology , Mice , Mitochondria/metabolism , Quinone Reductases
7.
Anaesthesia ; 69(4): 327-36, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24641639

ABSTRACT

The use of periclavicular brachial plexus block as regional anaesthesia for surgical procedures on the upper extremity is common. However, the proximity of the pleura results in a risk of pneumothorax. Without ultrasound monitoring, the pneumothorax risk has been reported to be as high as 6.1%. We conducted a prospective, observational study to examine the risk of pneumothorax in 6366 ultrasound-guided periclavicular plexus blocks. All patients with a clinically manifest and radiologically confirmed pneumothorax were analysed. Clinically symptomatic pneumothorax occurred in four patients (0.06%; 95% CI 0.001-0.124), in three of them after a two-day latency period. Ultrasound guidance does therefore appear to reduce the risk of pneumothorax. Although all of the anaesthesiologists involved in the complications had previously performed fewer than 20 blocks, we are not able to confirm that a block experience ≤ 20 is a significant risk factor. Faulty image-setting, inability to obtain a view of the needle tip and inadequate supervision are likely to be important risk factors.


Subject(s)
Brachial Plexus/diagnostic imaging , Nerve Block/adverse effects , Pneumothorax/epidemiology , Pneumothorax/etiology , Ultrasonography, Interventional/methods , Adult , Arm/surgery , Exostoses/surgery , Female , Ganglia, Sensory/surgery , Humans , Male , Middle Aged , Needles/adverse effects , Nerve Block/methods , Palmar Plate/surgery , Prospective Studies , Radius/surgery , Risk Factors , Smoking/adverse effects , Transcutaneous Electric Nerve Stimulation , Wrist/surgery , Young Adult
9.
Hippocampus ; 22(8): 1691-702, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22367974

ABSTRACT

Iron is a necessary substrate for neuronal function throughout the lifespan, but particularly during development. Early life iron deficiency (ID) in humans (late gestation through 2-3 yr) results in persistent cognitive and behavioral abnormalities despite iron repletion. Animal models of early life ID generated using maternal dietary iron restriction also demonstrate persistent learning and memory deficits, suggesting a critical requirement for iron during hippocampal development. Precise definition of the temporal window for this requirement has been elusive due to anemia and total body and brain ID inherent to previous dietary restriction models. To circumvent these confounds, we developed transgenic mice that express tetracycline transactivator regulated, dominant negative transferrin receptor (DNTfR1) in hippocampal neurons, disrupting TfR1 mediated iron uptake specifically in CA1 pyramidal neurons. Normal iron status was restored by doxycycline administration. We manipulated the duration of ID using this inducible model to examine long-term effects of early ID on Morris water maze learning, CA1 apical dendrite structure, and defining factors of critical periods including parvalbmin (PV) expression, perineuronal nets (PNN), and brain-derived neurotrophic factor (BDNF) expression. Ongoing ID impaired spatial memory and resulted in disorganized apical dendrite structure accompanied by altered PV and PNN expression and reduced BDNF levels. Iron repletion at P21, near the end of hippocampal dendritogenesis, restored spatial memory, dendrite structure, and critical period markers in adult mice. However, mice that remained hippocampally iron deficient until P42 continued to have spatial memory deficits, impaired CA1 apical dendrite structure, and persistent alterations in PV and PNN expression and reduced BDNF despite iron repletion. Together, these findings demonstrate that hippocampal iron availability is necessary between P21 and P42 for development of normal spatial learning and memory, and that these effects may reflect disruption of critical period closure by early life ID.


Subject(s)
Hippocampus/growth & development , Iron Deficiencies , Memory/physiology , Prenatal Exposure Delayed Effects/metabolism , Receptors, Transferrin/metabolism , Age Factors , Analysis of Variance , Animals , Animals, Newborn , Brain-Derived Neurotrophic Factor/metabolism , CA1 Region, Hippocampal/cytology , CA1 Region, Hippocampal/embryology , CA1 Region, Hippocampal/metabolism , CA3 Region, Hippocampal/cytology , CA3 Region, Hippocampal/embryology , CA3 Region, Hippocampal/metabolism , CHO Cells , Cricetinae , Dendrites/metabolism , Extracellular Matrix/metabolism , Female , Hippocampus/cytology , Hippocampus/embryology , Humans , Interneurons/metabolism , Iron/pharmacology , Iron, Dietary/metabolism , Maze Learning/drug effects , Memory Disorders/drug therapy , Mice , Mice, Inbred C57BL , Mice, Transgenic , Nerve Net/metabolism , Parvalbumins/metabolism , Pregnancy , Pyramidal Cells/embryology , Pyramidal Cells/metabolism , Receptors, Transferrin/genetics , Time Factors
10.
Anaesthesist ; 60(10): 950-62, 2011 Oct.
Article in German | MEDLINE | ID: mdl-21993475

ABSTRACT

BACKGROUND: Thoracic epidural analgesia (EDA) is thought to provide cardioprotective effects in patients undergoing noncardiac surgery. The results of two previous meta-analysis showed controversial conclusions regarding the impact of EDA on perioperative survival. The purpose of the present meta-analysis was to evaluate, whether thoracic EDA has the potential to reduce perioperative cardiac morbidity or mortality on the basis of available randomized controlled trials. PATIENTS AND METHODS: A systematic literature search was conducted in medical databases (Med-Line, EBM-Reviews, Embase, Biosis and Biological Abstracts) and relevant clinical trials including patients undergoing noncardiac surgery were evaluated by two independent investigators. All randomized controlled trials investigating the effects of thoracic EDA on perioperative outcome, published from 1980 up to the end of 2008 were included into this quantitative systematic review. Calculations were performed using the statistics program Review Manager 4.1 using a fixed-effects model. RESULTS: Nine studies with a total of 2,768 patients were included in the meta-analysis. Thoracic EDA did not reduce perioperative mortality [odds ratio (Peto OR): 1.08; 95% confidence interval (CI) 0.74-1.58]. Patients receiving thoracic EDA demonstrated a tendency to a lower rate of perioperative myocardial infarction. However, this effect of thoracic EDA did not reach statistical significance (Peto OR: 0.65; 95% CI 0.4-1.05). CONCLUSIONS: The present meta-analysis did not prove any positive influence of thoracic EDA on perioperative in-hospital mortality in patients undergoing noncardiac surgery. Furthermore, it remains questionable if thoracic EDA has the potential to reduce the rate of perioperative myocardial infarction.


Subject(s)
Anesthesia, Epidural , Heart Diseases/prevention & control , Anesthesia, Epidural/adverse effects , Anesthesia, General , Data Interpretation, Statistical , Heart Diseases/mortality , Hospital Mortality , Humans , Myocardial Infarction/epidemiology , Myocardial Infarction/mortality , Odds Ratio , Postoperative Complications/mortality , Randomized Controlled Trials as Topic , Surgical Procedures, Operative , Treatment Outcome
11.
Br J Anaesth ; 106(4): 580-9, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21296768

ABSTRACT

BACKGROUND: Thoracic epidural anaesthesia (EDA) is regarded as the 'gold standard' for postoperative pain control and restoration of pulmonary function after lung surgery. Easier, less time-consuming, and, perhaps, safer is intercostal nerve block performed under direct vision by the surgeon before closure of the thoracotomy combined with postoperative i.v. patient-controlled analgesia with morphine. We hypothesized that this technique is as effective as thoracic EDA. METHODS: The study was designed as a single-centre, open labelled, randomized non-inferiority trial. A total of 92 patients undergoing elective lung surgery were randomly assigned to the epidural (n=47) or intercostal group (n=45), and 83 patients completed the study. Pain scores, inspiratory vital capacity, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow rate (PEFR) were assessed during the first four postoperative days. RESULTS: Median treatment differences regarding pain scores at rest failed to demonstrate non-inferiority of the intercostal nerve block at the first postoperative day. Patients of the intercostal group reported significantly higher pain scores on coughing during the first and second postoperative days. The epidural group had a significantly higher median FVC, FEV1, and PEFR values on the second postoperative day. No difference was found in pulmonary complications, length of hospital stay, or in-hospital deaths. CONCLUSIONS: In patients undergoing lung surgery, single intercostal nerve block plus i.v. patient-controlled analgesia with morphine is not as effective as patient-controlled EDA with respect to pain control and restoration of pulmonary function.


Subject(s)
Anesthesia, Epidural/methods , Intercostal Nerves , Nerve Block/methods , Pain, Postoperative/prevention & control , Pneumonectomy , Adult , Aged , Analgesia, Patient-Controlled , Analgesics, Opioid/administration & dosage , Anesthesia, Epidural/adverse effects , Female , Forced Expiratory Volume , Humans , Lung/physiopathology , Male , Middle Aged , Morphine/administration & dosage , Nerve Block/adverse effects , Patient Satisfaction , Peak Expiratory Flow Rate , Prospective Studies , Thoracotomy , Vital Capacity , Young Adult
12.
Anaesthesia ; 65(11): 1085-93, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20860555

ABSTRACT

This study tested the hypothesis that propofol is associated with a higher hepatic blood flow in humans compared with desflurane. Using a cross over study design, 10 patients received first propofol and then desflurane, and a further 10 patients received desflurane and then propofol. Blood flow index in the right and middle hepatic veins, stroke volume index and cardiac index were assessed by transoesophageal echocardiography. Mean arterial blood pressure, stroke volume index and cardiac index were the same in both groups. Propofol was associated with significantly greater blood flow index in the right hepatic vein (median (IQR [range]) 199 (146-237 [66-388]) vs. 149 (112-189 [42-309]) ml.min(-1).m(-2); p = 0.005) and middle hepatic vein (150 (122-191 [57-341]) vs. 125 (92-149 [47-362]) ml.min(-1).m(-2); p < 0.001) compared with desflurane. In routine clinical conditions, propofol anaesthesia was associated with significantly greater hepatic blood flow than desflurane anaesthesia.


Subject(s)
Anesthetics, Inhalation/pharmacology , Anesthetics, Intravenous/pharmacology , Isoflurane/analogs & derivatives , Liver Circulation/drug effects , Propofol/pharmacology , Adult , Aged , Aged, 80 and over , Cross-Over Studies , Desflurane , Echocardiography, Transesophageal , Female , Hemodynamics/drug effects , Hepatic Veins/diagnostic imaging , Hepatic Veins/drug effects , Hepatic Veins/physiology , Humans , Isoflurane/pharmacology , Male , Middle Aged , Pilot Projects , Young Adult
13.
Br J Anaesth ; 104(3): 351-8, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20118146

ABSTRACT

BACKGROUND: Pain sensitizes the central nervous system via N-methyl-D-aspartate receptors (NMDARs) leading to an enhancement of pain perception. However, the enhanced responsiveness of pain-processing areas can be suppressed by subanaesthetic doses of the NMDAR antagonist xenon. To analyse the strength of the analgesic effect of low-dose xenon using new economical application methods, we tested xenon applied nasally in an experimental human pain setting. METHODS: We tested 10 healthy volunteers using a multimodal experimental pain testing in a randomized double-blind placebo-controlled repeated measures study. Xenon was administered using a novel low-pressure intranasal application device. Additionally, we measured xenon concentrations in blood samples obtained from intracranial veins of experimental animals to describe the pharmacokinetics of intranasally applied xenon in the cerebral compartment. RESULTS: Intranasal application of xenon at a rate of 1.0 litre h(-1) for 30 min significantly increased pain tolerance of volunteers to ischaemic (+128%), cold (+58%), and mechanical (+40%) stimulation (P<0.01). However, 60 min after terminating the application of xenon, there was no significant alteration of pain tolerance compared with placebo. Cranial blood concentrations of xenon in pigs reached a steady state of approximately 450 nl ml(-1) after 5 min. CONCLUSIONS: In this placebo-controlled experimental human study, we described the increased pain tolerance induced by intranasally applied xenon. On the basis of our results, we conclude that intranasally administered xenon has analgesic properties and suggest that the novel application device presented here offers new possibilities for the administration of NMDAR antagonists within a multimodal analgesia approach.


Subject(s)
Anesthetics, Inhalation/pharmacology , Pain Threshold/drug effects , Xenon/pharmacology , Administration, Intranasal , Adult , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/blood , Analgesics, Non-Narcotic/pharmacology , Anesthetics, Inhalation/administration & dosage , Anesthetics, Inhalation/blood , Animals , Cold Temperature , Disease Models, Animal , Double-Blind Method , Drug Delivery Systems , Humans , Ischemia/complications , Male , Pain/etiology , Pain/prevention & control , Pain Measurement/methods , Physical Stimulation/methods , Reaction Time/drug effects , Sus scrofa , Xenon/administration & dosage , Xenon/blood
14.
Eur Surg Res ; 43(1): 53-60, 2009.
Article in English | MEDLINE | ID: mdl-19439972

ABSTRACT

BACKGROUND: Endotoxemia is a crucial factor in the pathogenesis of sepsis. Elimination of endotoxin is aimed at the reduction of sepsis-related morbidity and lethality. The objective of this study was to examine the impact of an endotoxin adsorber on hemodynamics, O(2) exchange and metabolism during resuscitated porcine endotoxemia. METHODS: Twenty pigs were randomized into 2 intervention groups (n = 7 each) and 1 control group (n = 6). Endotoxemia was induced by continuous intravenous application of lipopolysaccharide for 8 h. Adsorber therapy was started at the same time as the induction of endotoxemia or 2 h later. An extracorporeal hemoperfusion device using immobilized human serum albumin for endotoxin adsorption was used. RESULTS: Hemodynamic, metabolic and acid-base parameters, as well as the kinetics of interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor-alpha, were characteristic for endotoxic shock. Endotoxin plasma levels were low (arterial, hepatic and portal vein). None of the parameters were significantly influenced by the adsorber system. CONCLUSION: Despite typical clinical signs of endotoxemia, the adsorber system had no significant effect on hemodynamic, metabolic and acid-base parameters during endotoxic shock. The reasons for the absence of an effect are elusive; however, failure of the method per se or exceeded capacity of the adsorber cannot be excluded.


Subject(s)
Endotoxemia/therapy , Endotoxins/metabolism , Hemoperfusion , Adsorption , Animals , Endotoxemia/metabolism , Endotoxemia/physiopathology , Endotoxins/blood , Female , Hemodynamics , Humans , Lipopolysaccharides/pharmacology , Male , Oxygen/metabolism , Swine , Time Factors
15.
Br J Pharmacol ; 155(6): 925-33, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19002104

ABSTRACT

BACKGROUND AND PURPOSE: Glutamate is the main excitatory neurotransmitter in the vertebrate CNS. Removal of the transmitter from the synaptic cleft by glial and neuronal glutamate transporters (GLTs) has an important function in terminating glutamatergic neurotransmission and neurological disorders. Five distinct excitatory amino-acid transporters have been characterized, among which the glial transporters excitatory amino-acid transporter 1 (EAAT1) (glutamate aspartate transporter) and EAAT2 (GLT1) are most important for the removal of extracellular glutamate. The purpose of this study was to describe the effect of the commonly used anaesthetic etomidate on glutamate uptake in cultures of glial cells. EXPERIMENTAL APPROACH: The activity of the transporters was determined electrophysiologically using the whole cell configuration of the patch-clamp recording technique. KEY RESULTS: Glutamate uptake was suppressed by etomidate (3-100 microM) in a time- and concentration-dependent manner with a half-maximum effect occurring at 2.4+/-0.6 microM. Maximum inhibition was approximately 50% with respect to the control. Etomidate led to a significant decrease of V(max) whereas the K(m) of the transporter was unaffected. In all cases, suppression of glutamate uptake was reversible within a few minutes upon washout. Furthermore, both GF 109203X, a nonselective inhibitor of PKs, and H89, a selective blocker of PKA, completely abolished the inhibitory effect of etomidate. CONCLUSION AND IMPLICATIONS: Inhibition of glutamate uptake by etomidate at clinically relevant concentrations may affect glutamatergic neurotransmission by increasing the glutamate concentration in the synaptic cleft and may compromise patients suffering from acute or chronic neurological disorders such as CNS trauma or epilepsy.


Subject(s)
Anesthetics, Intravenous/pharmacology , Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors , Etomidate/pharmacology , Glutamic Acid/metabolism , Neuroglia/metabolism , Animals , Animals, Newborn , Brain/cytology , Cells, Cultured , Dose-Response Relationship, Drug , Rats , Rats, Sprague-Dawley , Time Factors
16.
J Perinatol ; 26(3): 147-53, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16467857

ABSTRACT

OBJECTIVE: To examine the consequences of antenatal betamethasone (AB) exposure on postnatal stress regulation. STUDY DESIGN: Fourteen AB exposed infants born at 28-30 weeks' gestation were assessed in the NICU during postnatal week 1 and at 34 weeks postconception. Nine infants born at 34 weeks gestation without AB treatment were evaluated as a postconceptional age comparison group. Salivary cortisol, heart rate, and behavior were measured at baseline and in response to a heelstick blood draw. RESULTS: Repeated measures ANOVAs revealed that both groups displayed an increase in heart rate and behavioral distress in response to the stressor. The cortisol response, however, was blunted in AB-treated infants at both assessments. CONCLUSION: AB treatment has consequences for hypothalamic-pituitary-adrenal (HPA) axis regulation that persist for at least four to six weeks after birth, indicating that studies of long-term effects are warranted.


Subject(s)
Betamethasone/adverse effects , Infant, Premature , Pituitary-Adrenal System/drug effects , Prenatal Exposure Delayed Effects , Analysis of Variance , Apgar Score , Betamethasone/therapeutic use , Case-Control Studies , Cohort Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Gestational Age , Heart Rate/drug effects , Humans , Hydrocortisone/metabolism , Infant, Newborn , Intensive Care Units, Neonatal , Male , Pituitary-Adrenal Function Tests , Pituitary-Adrenal System/physiopathology , Pregnancy , Reference Values , Stress, Psychological , Time Factors
17.
Br J Anaesth ; 94(4): 479-85, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15695547

ABSTRACT

BACKGROUND: The anaesthetic, analgesic, and neuroprotective effects of xenon (Xe) are believed to be mediated by a block of the NMDA (N-methyl-D-aspartate) receptor channel. Interestingly, the clinical profile of the noble gas differs markedly from that of specific NMDA receptor antagonists. The aim of this study was, therefore, to investigate whether Xe might be less specific, also inhibiting the two other subtypes of glutamate receptor channels, such as the alpha-amino-3-hydroxy-5-methyl-4-isoxazolole propionate (AMPA) and kainate receptors. METHODS: The study was performed on voltage-clamped cortical neurones from embryonic mice and SH-SY5Y cells expressing GluR6 kainate receptors. Drugs were applied by a multi-barreled fast perfusion system. RESULTS: Xe, dissolved at approximately 3.45 mM in aqueous solution, diminished the peak and even more the plateau of AMPA and glutamate induced currents. At the control EC(50) value for AMPA (29 microM) these reductions were by about 40 and 56% and at 3 mM glutamate the reductions were by 45 and 66%, respectively. Currents activated at the control EC(50) value for kainate (57 microM) were inhibited by 42%. Likewise, Xe showed an inhibitory effect on kainate-induced membrane currents of SH-SY5Y cells transfected with the GluR6 subunit of the kainate receptor. Xe reduced kainate-induced currents by between 35 and 60%, depending on the kainate concentration. CONCLUSIONS: Xe blocks not only NMDA receptors, but also AMPA and kainate receptors in cortical neurones as well as GluR6-type receptors expressed in SH-SY5Y cells. Thus, Xe seems to be rather non-specific as a channel blocker and this may contribute to the analgesic and anaesthetic potency of Xe.


Subject(s)
Anesthetics, Inhalation/pharmacology , Cerebral Cortex/drug effects , Neurons/drug effects , Xenon/pharmacology , Animals , Cells, Cultured , Cerebral Cortex/cytology , Cerebral Cortex/physiology , Excitatory Amino Acid Antagonists/pharmacology , Glutamic Acid/pharmacology , Kainic Acid/antagonists & inhibitors , Kainic Acid/pharmacology , Membrane Potentials/drug effects , Membrane Potentials/physiology , Mice , Mice, Inbred BALB C , Neurons/physiology , Patch-Clamp Techniques , Receptors, AMPA/drug effects , Receptors, Glutamate/drug effects , Receptors, Kainic Acid/drug effects , Receptors, Kainic Acid/genetics , Receptors, Kainic Acid/physiology , Transfection , Tumor Cells, Cultured , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/antagonists & inhibitors , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology , GluK2 Kainate Receptor
18.
Acta Anaesthesiol Scand ; 47(9): 1119-24, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12969106

ABSTRACT

BACKGROUND: Over the past decade hyperpolarized (129)xenon incorporated in lipid emulsions has been studied for the purpose of imaging enhancement in radiology. Xenon (Xe), a NMDA (N-methyl-D-aspartate)-receptor antagonist, has neuroprotective properties even at subanesthetic concentrations. Thus, its intravenous administration for this purpose deserves further evaluation. In this study, we investigated in an in vitro model the effect of Xe, incorporated in a lipid emulsion (Lipofundin MCT(R) 20%), on the NMDA receptor channel of cortical neurons of the mouse. METHODS: Pulses of 50 micro M of NMDA solution were extracellularly applied to the cells for 10 s, and the elicited membrane currents (I) were recorded while the membrane potential (V) was clamped at -80 mV. Either Lipofundin MCT(R) 20% or aqueous solution was loaded with Xe and applied simultaneously with the NMDA pulses by means of a multibarreled pipette attached to a battery of infusion-pumps. RESULTS: Xenon equilibrated in Lipofundin(R) caused a concentration-dependent and reversible inhibition of NMDA-induced currents (maximal Xe content [Xemax]: 190 micro l ml-1). The inhibitory effect was equivalent compared with the effect of Xe dissolved in aqueous solution (Xemax: 89 micro l ml-1) even though the Xe content of the lipid solution was almost doubled. Further enhancement of the Xe content by saturating both the lipid emulsion and the aqueous solutions with Xe (Xemax: 256 micro l ml-1) did not increase the inhibitory action on NMDA-receptors. CONCLUSION: The data demonstrate that Xe dissolved in Lipofundin MCT(R) 20% inhibits NMDA-receptors. Lipid emulsions enriched with Xe may serve as a carrier and a reservoir for Xe.


Subject(s)
Ion Channels/antagonists & inhibitors , Phospholipids/administration & dosage , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Sorbitol/administration & dosage , Xenon/administration & dosage , Animals , Dose-Response Relationship, Drug , Drug Combinations , Female , Male , Mice , Mice, Inbred BALB C
19.
Anaesthesist ; 52(6): 500-6, 2003 Jun.
Article in German | MEDLINE | ID: mdl-12835870

ABSTRACT

BACKGROUND: The purpose of the study was to investigate the effect of modified neuroleptanesthesia (NLA) with fentanyl/midazolam on the catabolic responses during and after abdominal surgery. METHODS: A total of 13 patients undergoing cystoprostatectomy received either modified NLA ( n=7) or inhaled anesthesia with isoflurane (ISO, n=6). Glucose and urea production rates were assessed before, during and 1 day after the operation. Plasma concentrations of glucose, urea, lactate, insulin, glucagon and cortisol were also determined. RESULTS: In contrast to isoflurane anesthesia, modified NLA prevented an increase in plasma glucose concentration and glucose production during ( P<0.05), but not after surgery. There were no differences in perioperative urea production rates or plasma concentrations of urea, insulin, glucagon and lactate between the two groups. Modified NLA suppressed the intraoperative increase in plasma cortisol concentration as observed in the ISO group ( P<0.05). CONCLUSION: Modified NLA inhibits the increase in plasma glucose concentration and glucose production as seen during isoflurane anesthesia. However, NLA does not influence the catabolic response on the first postoperative day.


Subject(s)
Abdomen/surgery , Anesthesia, Inhalation , Anesthesia, Intravenous , Anesthetics, Inhalation , Anesthetics, Intravenous , Fentanyl , Isoflurane , Midazolam , Stress, Physiological/physiopathology , Aged , Blood Glucose/metabolism , Heart Rate/physiology , Humans , Hydrocortisone/blood , Male , Middle Aged , Postoperative Period , Prostatectomy , Urea/blood
20.
Anaesthesist ; 52(6): 540-8, 2003 Jun.
Article in German | MEDLINE | ID: mdl-12835877

ABSTRACT

Portable digital assistants (PDAs) may be of value to the anaesthesiologist as development in medical care is moving towards "bedside computing". Many different portable computers are currently available and it is now possible for the physician to carry a mobile computer with him all the time. It is data base, reference book, patient tracking help, date planner, computer, book, magazine, calculator and much more in one mobile device. With the help of a PDA, information that is required for our work may be available at all times and everywhere at the point of care within seconds. In this overview the possibilities for the use of PDAs in anaesthesia and intensive care medicine are discussed. Developments in other countries, possibilities in use but also problems such as data security and network technology are evaluated.


Subject(s)
Ambulances , Anesthesiology/methods , Critical Care/methods , Microcomputers , Point-of-Care Systems , Computer Communication Networks , Databases, Factual , Diagnosis-Related Groups , Humans , Internet , Monitoring, Physiologic
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