Serum neurofilament light as a potential marker of illness duration in bipolar disorder.

INTRODUCTION: Investigation on specific biomarkers for diagnostic or prognostic usage in mental diseases and especially bipolar disorder BD seems to be one outstanding field in current research. Serum neurofilament light (sNfL), a marker for neuro-axonal injury, is increased in various acute and chronic neurological disorders, but also neuro-psychiatric conditions, including affective disorders. The aim of our study was to determine a potential relation between a neuron-specific marker like sNfL and different clinical states of BD. METHODS: In the current investigation, 51 patients with BD and 35 HC were included. Mood ratings with the Hamilton depression scale (HAMD) and the Young mania rating scale (YMRS) have been included. Illness duration was defined as the period from the time of diagnosis out of self-report and medical records. sNFL was quantified by a commercial ultrasensitive single molecule array (Simoa). RESULTS: There was a significant positive correlation between the number of manic episodes in the past and sNfL, controlled for age and duration of illness. (R = 0.49, p = 0.03) Depressive episodes were not associated to sNfL values. (R = 0.311, p = n.s.) Patients with >3 years of illness duration showed significantly higher levels of sNfL (M18.59; SD 11.89) than patients with shorter illness duration (M = 12.38, p = 0.03) and HC (M = 11.35, p = 0.02). Patients with <3 years of illness and HC did not differ significantly in sNfL levels. DISCUSSION: Interestingly, individuals with BD and HC did not differ in sNFL levels in general. Nevertheless, looking at the BD cohort more specifically, we found that individuals with BD with longer duration of illness (>3 years) had higher levels of sNfL than those with an illness duration below 3 years. Our results confirm previous reports on the relation of neuro-axonal injury as evidenced by sNfL and illness specific variables in bipolar disorder. Further studies are needed to clarify if sNfL may predict the disease course and/or indicated response to treatment regimes.

A one-year view on the association of metabolic syndrome and cognitive function in bipolar disorder - Preliminary data.

BACKGROUND: Individuals with bipolar disorder have a high prevalence of metabolic syndrome and an increased risk for cognitive deficits. The aim of this longitudinal study was to investigate the trajectory of cognitive decline in dependence of metabolic syndrome over a one-year interval. METHODS: 52 well-diagnosed individuals with bipolar disorder, euthymic at baseline and follow-up (n = 17 with metabolic syndrome vs. n = 35 without metabolic syndrome) were investigated with a comprehensive neurocognitive test battery (Trail Making Test A/B, Digit Symbol Test, California Verbal Leaning Test, or the Verbal Learning and Memory Test respectively) twice within the interval of one year. RESULTS: Patients with bipolar disorder and additional metabolic syndrome performed significantly worse in the domain of psychomotor and processing speed/attention than patients without metabolic syndrome at test point one. No deteriorating effects of metabolic syndrome on the cognitive domain scores and overall cognitive performance were found at the one-year follow up. However, no cognitive decline could be reported in both groups. LIMITATIONS: Time interval, small sample size and selection of metabolic syndrome affected patients were the major limitations of this study. CONCLUSION: There was no association of metabolic syndrome on the one-year trajectory of cognitive function in bipolar disorder. Future studies should expand the observation period and investigate larger samples.

Gene expression analysis of MAOA and the clock gene ARNTL in individuals with bipolar disorder compared to healthy controls.

INTRODUCTION: Circadian rhythms are associated with bipolar disorder (BD). This cross-sectional study aimed at investigating ARNTL and MAOA gene expression differences (1) between individuals with BD and controls, (2) between affective episodes, and (3) the relationship between ARNTL and MAOA expression. METHODS: ARNTL and MAOA gene expression in peripheral mononuclear blood cells were analysed from fasting blood samples (BD n = 81, controls n = 54) with quantitative real-time PCR operating on TaqMan® assays (normalised to 18S RNA expression). ANCOVAs corrected for age, sex, body mass index, and medication was used to evaluate expression differences and correlation analyses for the relation between ARNTL and MAOA expression. RESULTS: ARNTL gene expression differed between affective episodes (F(2,78) = 3.198, p = 0.047, Partial Eta2= 0.083), but not between BD and controls (n.s.). ARNTL and MAOA expression correlated positively in BD (r = 0.704, p < 0.001) and in controls (r = 0.932, p < 0.001). MAOA expression differed neither between BD and controls nor between affective episodes (n.s.). DISCUSSION: Clock gene expression changes were observed in different affective states of BD. More precisely, ARNTL gene expression was significantly higher in euthymia than in depression. ARNTL and MAOA gene expression correlated significantly in BD and in controls, which emphasises the strong concatenation between circadian rhythms and neurotransmitter breakdown.

Sex differences in zonulin in affective disorders and associations with current mood symptoms.

INTRODUCTION: The bidirectional connection between the brain and the gut within psychiatric entities has gained increasing scientific attention over the last years. As a regulator of intestinal permeability, zonulin acts as a key player on the interface of this interplay. Like several psychiatric disorders, intestinal permeability was associated with inflammation in previous findings. METHODS: In this study we explored differences in zonulin serum levels in currently depressed (n = 55) versus currently euthymic (n = 37) individuals with an affective disorder. Further, we explored sex differences and possible influences on zonulin and affective symptoms like medication, age, body mass index, and smoking status. RESULTS: Serum zonulin was significantly higher in females than in men independent from affective status (z = -2.412, p = .016). More specifically, females in the euthymic subgroup had higher zonulin levels than euthymic men (z = -2.114, p = .035). There was no difference in zonulin serum levels in individuals taking or not taking a specific psychopharmacotherapy. We found no correlation between zonulin serum levels and depression severity. DISCUSSION: Increased serum zonulin levels as a proxy for increased intestinal permeability in women may indicate a state of elevated susceptibility for depression-inducing stimuli.

The association between anti-inflammatory effects of long-term lithium treatment and illness course in Bipolar Disorder.

INTRODUCTION: Altered levels of acute-phase proteins are often described in different conditions in BD. Nevertheless, data on the association between lithium treatment and inflammatory markers in the long-term course of BD are still missing. The aim of the study was to examine the long-term course of BD concerning long-term lithium treatment, chronic inflammatory processes and symptom progression. Furthermore, the association between duration of lithium treatment and levels of hsCRP was explored. METHODS: 267 individuals (males= 139, females= 128) with BD were included. Duration of lithium treatment as well as symptom progression, defined as the increase in severity of symptoms, number of episodes a year and duration of episodes within a period of 1.5 years in the past and hsCRP were evaluated. RESULTS: Male individuals with symptom progression over time had significantly lower duration of lithium treatment compared to individuals without symptoms progression (U= 47.4, p=.037). There were significantly higher levels of hsCRP in male individuals with symptom progression compared to males without symptom progression (U= 47.5, p=.027). Further, there was a significant negative correlation between the duration of lithium treatment and hsCRP levels in the whole sample (r= -.276, p<.05). CONCLUSION: Our results show that an altered inflammatory state may be associated with a more severe illness course in BD. Further, a longer duration of lithium treatment may be associated with lower symptom progression. The shown association between hsCRP-levels and lithium treatment duration suggests a potential anti-inflammatory effect of lithium as a mediator of its significant positive outcome effect in BD.

The relationship between "Eyes Reading" ability and verbal memory in bipolar disorder.

In psychiatric disorders, neurocognitive impairments are prevalent and have been associated with poor outcome. Deficits in Theory of Mind (ToM, "mentalising") have also been observed in bipolar disorder (BD); however, the literature shows inconsistent data. The aim of this study was to explore ToM performance in a well-characterized sample of euthymic individuals with BD and its relationship with neurocognitive function. One hundred sixteen euthymic patients with BD between 18 and 74 years (mean age = 42.4, SD = 13.8) and 79 healthy controls (mean age = 39.8, SD = 16.5) were investigated with an extensive neurocognitive test battery (Trail Making Test A/B, d2 Test of Attention, Stroop Color-Word Test, California Verbal Learning Test, Multiple Choice Vocabulary Test). Additionally, all participants were given the Reading the Mind in the Eyes Test (RMET) to measure affective ToM, the ability to make assumptions about other people´s feelings. Overall, "Eyes Reading" performance was not impaired in individuals with BD compared with controls. However, a significant relationship between RMET and verbal memory in BD was shown, particularly in males. Data showed worse RMET performance in patients with memory deficits compared to patients without memory deficits and controls. Due to cross-sectional data, no conclusions can be made with respect to cause and effect.

Epigenetics of the molecular clock and bacterial diversity in bipolar disorder.

Objectives The gut microbiome harbors substantially more genetic material than our body cells and has an impact on a huge variety of physiological mechanisms including the production of neurotransmitters and the interaction with brain functions through the gut-brain-axis. Products of microbiota can affect methylation according to preclinical studies. The current investigation aimed at analyzing the correlation between gut microbiome diversity and the methylation of the clock gene ARNTL in individuals with Bipolar Disorder (BD). Methods Genomic DNA was isolated from fasting blood of study participants with BD (n = 32). The methylation analysis of the ARNTL CG site cg05733463 was performed by bisulfite treatment of genomic DNA with the Epitect kit, PCR and pyrosequencing. Additionally, DNA was extracted from stool samples and subjected to 16S rRNA sequencing. QIIME was used to analyze microbiome data. Results Methylation status of the ARNTL CpG position cg05733463 correlated significantly with bacterial diversity (Simpson index: r= -0.389, p = 0.0238) and evenness (Simpson evenness index: r= -0.358, p = 0.044). Furthermore, bacterial diversity differed significantly between euthymia and depression (F(1,30) = 4.695, p = 0.039). Discussion The results of our pilot study show that bacterial diversity differs between euthymia and depression. Interestingly, gut microbiome diversity and evenness correlate negatively with methylation of ARNTL, which is known to regulate monoamine oxidase A transcription. We propose that alterations in overall diversity of the gut microbiome represent an internal environmental factor that has an epigenetic impact on the clock gene ARNTL which is thought to be involved in BD pathogenesis.

Changes in the tryptophan-kynurenine axis in association to therapeutic response in clinically depressed patients undergoing psychiatric rehabilitation.

INTRODUCTION: In recent decades a number of studies have shown an association between the Tryptophan (Trp)-Kynurenine (Kyn) axis and neuropsychiatric disorders. However, the role of the Trp-Kyn pathway on the affective status in a general psychiatric cohort requires clarification. This study aimed to measure peripheral changes in Trp, Kyn and the Kyn/Trp-ratio as well as in the inflammatory markers high sensitive C-reactive protein (hsCRP) and interleukine-6 (IL-6) in individuals undergoing a six-week course of intensive treatment program comparing subgroups of treatment responders and non-responders. METHODS: In this investigation 87 currently depressed individuals with a life-time history of depressive disorders were divided into treatment responders (n = 48) and non-responders (n = 39). The individuals were selected for an extreme group comparison out of 598 patients undergoing a 6-week psychiatric rehabilitation program in Austria. Responders were defined according to great changes in Becks Depression Inventory (BDI-II) between time of admission and discharge (BDI-II > 29 to BDI-II <14), while non-responders had no or minimal changes (BDI >20, max. 4 points change over time). Differences in the levels of Trp, Kyn, and the Kyn/Trp ratio as well as levels of hsCRP and IL-6, were compared between groups. Differences were analyzed at the time of admission as well as at discharge. RESULTS: A significant group x time interaction was found for Kyn [F(1.82) = 5.79; p = 0.018] and the Kyn/Trp ratio [F(1.85) = 4.01, p = 0.048]. Importantly, Kyn increased significantly in the non-responder group, while the Kyn/Trp ratio decreased significantly in the responder group over time. Furthermore, changes in Kyn as well as hsCRP levels correlated significantly with changes in the body mass index over time (Kyn: r=0.24, p = 0.030; hsCRP: r=0.25, p = 0.021). No significant interactions were found for Trp and hsCRP, although they increased significantly over time. DISCUSSION: Given the limitations of the study, we could show that the therapeutic response to a multimodal treatment in clinically depressed patients not receiving cytokine treatment is associated with changes in Kyn levels and the Kyn/Trp ratio as well as with hsCRP. However, it is too early to draw any causal conclusion. Future research should clarify relevant clinical and neurobiological parameters associated with changes in Kyn levels and Kyn/Trp ratio, especially in regard to clinical response.

The role of tryptophan metabolism and food craving in the relationship between obesity and bipolar disorder.

BACKGROUND & AIMS: Individuals with bipolar disorder (BD) have a significantly increased risk of obesity-related conditions. The imbalance between food intake and energy expenditure is assumed to be a major risk factor for obesity in BD. This study analyzed food craving in relation to anthropometric, metabolic, and neurobiological parameters in a well-characterized cohort of euthymic individuals with BD. METHODS: One-hundred-thirty-five patients completed the Food-Craving Inventory assessing four categories of food craving (fat, fast-food, sweets and carbohydrate craving). Additionally, clinical, metabolic and anthropometric parameters were assessed. RESULTS: Higher levels of fat craving were observed in males, versus females, with BD. High levels of carbohydrate craving positively correlated with kynurenine and the kynurenine-to-tryptophan ratio. Higher serum nitrite and neopterin levels were related to fat craving. Parameters of fat metabolism (triglycerides, high-density lipoprotein) were associated with fat and fast-food craving. Anthropometric measures of obesity (e.g. body mass index, waist-to-hip-ratio) were not related to food craving. CONCLUSIONS: Overweight/obese individuals with BD show an increased driving of tryptophan down the kynurenine pathways, as indicated by an increase in the serum kynurenine-to-tryptophan ratio. The driving of tryptophan down the kynurenine pathway is mediated by immune-inflammatory activity and stress. The correlation of increased kynurenine with food craving, especially carbohydrate craving, probably indicates a regulatory deficit in the maintenance of chronic inflammatory processes in obesity and BD. Food craving seems to be of clinical importance in the treatment of metabolic disturbances in BD, although not associated with anthropometric measures of obesity. Rather, food craving correlates with blood metabolic parameters and an increased activation of the kynurenine pathway, both of which are linked to higher affective symptomatology and the development of cardiovascular diseases.

Gender differences in the association between physical activity and cognitive function in individuals with bipolar disorder.

INTRODUCTION: Bipolar disorder (BD) is accompanied by a high number of comorbidities and associated with an overall increased mortality. Especially obesity, systemic inflammatory processes and cognitive deficits are highly prevalent and increase with the course of illness. Physical activity (PA) is associated with beneficial effects on somatic comorbidities such as obesity or cardiovascular disease in individuals without psychiatric disorder. Furthermore, PA might increase neurocognitive performance and reduce systemic inflammation. OBJECTIVE: The aim of the study was to investigate the association between PA and neurocognitive function in euthymic individuals suffering from BD. METHODS AND PARTICIPANTS: 120 individuals with BD, euthymic at test time, completed the self-reported International Physical Activity Questionnaire (IPAQ) assessing PA of the past seven days and were accordingly assigned to a specific activity category (low, moderate or vigorous). Furthermore, clinical parameters were gathered and cognitive tests analysing verbal-dependent intelligence, attention, executive functioning as well as memory were administered. RESULTS: Female individuals in the vigorous PA group performed significantly higher in most of the cognitive domains compared to females with moderate or low PA. In males, we only found a significant difference in one test for attention between moderate/vigorous and the low activity group. CONCLUSION: Differences between PA groups in cognitive performance in female individuals with BD were obvious in almost all cognitive domains. As cognitive deficits are strongly associated with a worse course of disease and outcome, PA might offer a concomitant therapy targeting not only somatic comorbidities such as obesity and cardiovascular disease, but also neurocognition.

Conserved Senescence Associated Genes and Pathways in Primary Human Fibroblasts Detected by RNA-Seq.

Cellular senescence correlates with changes in the transcriptome. To obtain a complete view on senescence-associated transcription networks and pathways, we assessed by deep RNA sequencing the transcriptomes of five of the most commonly used laboratory strains of human fibroblasts during their transition into senescence. In a number of cases, we verified the RNA-seq data by real-time PCR. By determining cellular protein levels we observed that the age-related expression of most but not all genes is regulated at the transcriptional level. We found that 78% of the age-affected differentially expressed genes were commonly regulated in the same direction (either up- or down-regulated) in all five fibroblast strains, indicating a strong conservation of age-associated changes in the transcriptome. KEGG pathway analyses confirmed up-regulation of the senescence-associated secretory phenotype and down-regulation of DNA synthesis/repair and most cell cycle pathways common in all five cell strains. Newly identified senescence-induced pathways include up-regulation of endocytotic/phagocytic pathways and down-regulation of the mRNA metabolism and the mRNA splicing pathways. Our results provide an unprecedented comprehensive and deep view into the individual and common transcriptome and pathway changes during the transition into of senescence of five human fibroblast cell strains.

Abdominal obesity is associated with impaired cognitive function in euthymic bipolar individuals.

OBJECTIVES: Overweight/obesity has been implicated to play a role in cognitive deficits in bipolar disorder (BD). This study aims to identify the relationship between body fat distribution and different domains of cognition in BD during euthymia. METHODS: A sample of 100 euthymic individuals with BD was measured with a cognitive test battery (i.e., Trail Making Test-A-B/TM-A/B, d2 Test of Attention, Stroop test, California Verbal Learning Test/CVLT) and an anthropometric measures set (body mass index, waist circumference, hip circumference, waist-to-hip-ratio, waist-to-height-ratio, and lipometry). Patient data were compared with a healthy control group (n = 64). RESULTS: Results show that overweight patients with BD exhibit lower performance in the TMT-A/B as well as in the free recall performance of the CVLT compared to normal-weight patients with BD and controls. In bipolar individuals, (abdominal) obesity was significantly associated with a poor cognitive performance. In bipolar females, associations with measures of verbal learning and memory were found; in bipolar males, associations with poor performance in the TMT-A/B and in the Stroop interference task were demonstrated. In controls, no associations were found. CONCLUSIONS: There are several possible pathways moderating the association between obesity and cognition in BD. Anthropometric and lipometry data underline the substantial mediating impact of body fat distribution on cognition in BD.

Peripheral markers of oxidative stress and antioxidative defense in euthymia of bipolar disorder--Gender and obesity effects.

INTRODUCTION: Oxidative and nitrosative stress are implicated in the pathogenesis of uni- and bipolar disorder. Herein we primarily sought to characterize markers of oxidative/nitrosative stress during euthymia in adults with bipolar disorder (BD). Oxidative markers were further evaluated in this BD sample in synopsis with excess overweight or obesity and/or comorbid metabolic syndrome (MetS). METHODS: Peripheral markers of oxidative stress [i.e. thiobarbituric acid reactive substance, (TBARS), malondialdehyde (MDA), and carbonyl proteins] and antioxidant markers [e.g. total antioxidative capacity (TAC), superoxide dismutase (SOD), glutathione S-transferase (GST)] were obtained in a cohort of euthymic adults with BD (N=113) and compared to healthy controls (CG) (N=78). Additionally, anthropometric measures included the body mass index (BMI) [kg/m(2)], waist and hip circumference [cm], waist-to-hip-ratio (WHR), waist to height ratio (WtHR) as well as the IDF-defined MetS. RESULTS: The major finding was a significantly decreased TAC in BD compared to the CG (p<0.01; BD: M 1.18, SD 0.47; CG: M 1.39, SD 0.49). MDA was significantly and TBARS by trend higher in the CG compared to the euthymic bipolar test persons (MDA: p<0.01, BD: M 0.70, SD 0.18; CG: M 0.81, SD 0.25; TBARS: p<0.1, BD: M 0.78, SD 0.28; CG: M 0.76, SD 0.30). The antioxidative enzyme GST was significantly elevated in both patients and controls (BD: M 298.24, SD 133.02; CG: M 307.27 SD 118.18). Subgroup analysis revealed that the CG with concurrent MetS and obesity had significantly elevated TAC when compared to CG without concurrent MetS (p<0.05, no MetS: M 1.33, SD 0.50; MetS: M 1.67, SD 0.32), as well as persons with BD with or without current MetS (no MetS: M 1.18, SD 0.44; MetS: M 1.15, SD 0.49). Significant correlations between GST and anthropometric variables were found in male study participants. Multivariate analysis indicated a significant gender effect concerning TBARS values in all patients and CG (p<0.01, females: M 0.73, SD 0.29; males: M 0.83, SD 0.28). CONCLUSION: Euthymic bipolar adults exhibit peripheral evidence of a disturbed biosignature of oxidative stress and antioxidative defense. Male test persons showed significantly higher peripheral markers of oxidative stress than women- female sex may exert protective effects. Furthermore, the biosignature of oxidative stress obtained herein was more pronounced in males with concurrent metabolic disorders. Our results further extend knowledge by introducing the moderating influence of gender and obesity on oxidative stress and BD.

[Austrian interdisciplinary recommendations on pediatric perioperative pain management: background, aims, methods and key messages]. / Österreichische interdisziplinäre Handlungsempfehlungen zum perioperativen Schmerzmanagement bei Kindern : Hintergrund, Ziel, Methodik und Kernaussagen.

These recommendations were originally commissioned by the"Österreichische Gesellschaft für Anästhesiologie, Reanimation und Intensivmedizin" (ÖGARI, Austrian Society for Anesthesiology, Resuscitation and Intensive Care Medicine). Against this background, Austrian experts from the disciplines anesthesiology, pain management, pediatrics and the "Berufsverband Kinderkrankenpflege" (Professional Association of Pediatric Nursing) have with legal support developed evidence-based and consensus recommendations for the clinical practice. The recommendations include key messages which cover the most important recommendations for the individual topics. The complete recommendations on pediatric perioperative pain management consist of seven separate articles which each deal with special sub-topics with comments on and explanations of the key messages. The target groups of the recommendations are all medical personnel of the individual disciplines involved in the treatment of perioperative and posttraumatic pain for neonates, infants and children up to 18 years old.

[Regional anesthesia procedures in childhood: Austrian interdisciplinary recommendations on pediatric perioperative pain management]. / Regionalanästhesiologische Verfahren im Kindesalter : Österreichische interdisziplinäre Handlungsempfehlungen zum perioperativen Schmerzmanagement bei Kindern.

Regional anesthesia should be used for children whenever possible and is an essential element of a multimodal pain management. The prerequisites for a safe and effective procedure are detailed knowledge of the anatomical, physiological and pharmacological differences in childhood, the use of age-appropriate equipment and rapid recognition and treatment of possible complications. Extensive experience in pediatric as well as regional anesthesia is essential. The rule for selection of the ideal regional anesthesia procedure for each individual patient is: as central as necessary and as peripheral as possible. A risk-benefit assessment must always be carried out. Very specialized techniques, such as thoracic and lumbar epidural anesthesia in childhood must be reserved for specialist pediatric anesthesia centers because experience is necessary which can only be acquired and maintained from a large number of cases. Technically simple procedures, such as caudal anesthesia, penis root block and wound infiltration are, however, also very effective. Even if the evidence is still lacking, ultrasound-guided placement of regional anesthesia is nowadays the method of choice for children. The use will lead to an increased level of acceptance and user-friendliness of the procedure in childhood. This article presents recommendations which demonstrate those points that must be generally observed when carrying out regional anesthesia in children. An overview of the regional anesthesia procedure in children is given.

Phylogeny, genetic variability and colour polymorphism of an emerging animal model: the short-lived annual Nothobranchius fishes from southern Mozambique.

Nothobranchius are a group of small, extremely short-lived killifishes living in temporary savannah pools in Eastern Africa and that survive annual desiccation of their habitat as dormant eggs encased in dry mud. One mitochondrial (COI) and three nuclear (CX32.2, GHITM, PNP) loci were used to investigate the phylogenetic relationship of Nothobranchius species from southern and central Mozambique. This group shows marked variation in captive lifespan at both the inter- and intraspecific levels; lifespan varies from a few months to over a year. As their distribution encompasses a steep gradient between semi-arid and humid habitats, resulting in contrasting selection pressures on evolution of lifespan and associated life history traits, Mozambican Nothobranchius spp. have recently become a model group in studies of ageing, age-related disorders and life history evolution. Consequently, intraspecific genetic variation and male colour morph distribution was also examined in the recovered clades. Using Bayesian species tree reconstruction and single loci analyses, three large clades were apparent and their phylogenetic substructure was revealed at the inter- and intra-specific levels within those clades. The Nothobranchius furzeri and Nothobranchius orthonotus clades were strongly geographically structured. Further, it was demonstrated that male colour has no phylogenetic signal in N. furzeri, where colour morphs are sympatric, but is associated with two reciprocally monophyletic groups in Nothobranchius rachovii clade, where colour morphs are parapatric. Finally, our analysis showed that a polymorphism in the Melanocortin1 receptor gene (which controls pigmentation in many vertebrates and was a candidate gene of male colouration in N. furzeri) is unrelated to colour phenotypes of the study species. Our results raise significant implications for future comparative studies of the species and populations analysed in the present work.

[Tonsillotomy and adenotonsillectomy in childhood. Study on postoperative pain therapy]. / Tonsillotomien und Adenotomien im Kindesalter. Studie zu postoperativen Schmerztherapie.

BACKGROUND: The primary aim of this study was to determine whether the combination of i.v. ketoprofen and i.v. paracetamol provides superior postoperative analgesia in children undergoing adenoidectomy or tonsillotomy compared to either drug alone. The secondary goal was to assess the time until rescue analgesia was needed, propofol requirements and the incidence of vomiting and time of discharge from the postanaesthesia recovery unit (PARU). METHODS: This double-blinded study included 120 children (aged 3-13 years) scheduled for elective tonsillectomy, adenoidectomy or adenotonsillectomy. The children were randomly assigned to one of 3 groups of 40 children each, using the sealed envelope method. The children received i.v. ketoprofen 2 mg/kgBW (group 1) or paracetamol 15 mg/kgBW (group 2) or the combination of these 2 drugs (group 3) after induction of anaesthesia. Standardized general anaesthesia consisted of sevoflurane and fentanyl at a dose of 2-3 µg/kgBW. Pain was assessed using a 5-point scoring system based on the Smiley scale. The Smiley scale shows various faces from a laughing face which corresponds to the state of no pain to a very unhappy face which corresponds to the situation of worst pain (1: no pain, 2: mild pain, 3: moderate pain, 4: severe pain, 5: worst pain). Pain was assessed at 30 min, 1 h, 2 h, 3 h and 4 h after arriving in the PACU. If the pain score exceeded 2 an i.v. dose of 0.1 mg/kgBW morphine was administered as rescue analgesia. RESULTS: During the stay in the PACU the children in the combination group required significantly less supplementary rescue analgesia than children in the ketoprofen and paracetamol groups (17.5% versus 30.8% versus 45%, respectively, χ(2) analysis <0.05). Pain scoring was highest after paracetamol, however, this difference was only significant when compared to the group receiving the combination of paracetamol and ketoprofen (U-test p<0.05). Rescue analgesia was administered earliest in group 2 (paracetamol) reaching statistical significance, however, only when compared to group 3 (logrank test p<0.05). Propofol requirements and time to discharge from the PACU did not differ significantly between the 3 groups (χ(2) analysis; U-test; p>0.05). The overall incidence of vomiting was very low in this study with 6.4% (9/139). Significantly more children in the paracetamol group compared to ketoprofen group and combination group suffered from vomiting (17.5% versus 2.6% versus 2.5%; χ(2) analysis; p<0.05). The time to discharge from PACU did not differ significantly between the 3 groups (U-test: p>0.05). CONCLUSION: The combination of i.v. paracetamol and i.v. ketoprofen provides superior postoperative analgesia compared to the single use of paracetamol.

Consecutive, prospective case series of a new method for ultrasound-guided supraclavicular approach to the brachiocephalic vein in children.

BACKGROUND: During ultrasound (US)-guided cannulation of the subclavian vein (SCV) via an infraclavicular route, the view of the needle behind the clavicle may be obscured. This study describes the US-guided supraclavicular cannulation of the brachiocephalic vein (BCV). METHODS: The 25 mm broadband linear array US probe was placed in the supraclavicular region to obtain a longitudinal view of the BCV beginning at the junction of the internal jugular vein and SCV. Using the in-plane technique, the needle was directed under US guidance into the BCV. RESULTS: Forty-two cannulations in 35 patients (aged 26 months-8 yr, weight range 0.96-21 kg) were included. Central venous catheter placement was successful in all children. In 31 patients (73.8%), the BCV was successfully punctured on the first attempt, in six patients (14.2%) after two attempts, and in five patients (11.9%) after three attempts. Significantly more puncture attempts were needed in the smaller weight and younger children, whereas the time course of the study had no significant impact on the success rate. CONCLUSIONS: This US-guided method offers a new possibility for central venous line placement in small children. It provides good needle guidance without any disturbing US shadow caused by bony structures.

Colonización nasal bacteriana en población sana de la ciudad de Santiago de Chile: ¿existe portación de Staphylococcus aureus meticilino resistente comunitario? / Nasal bacterial colonization in healthy people of the city of Santiago of Chile: is there nasal carriage of community methicillin resistant Staphylococcus aureus?

Introducción: No existe consenso en cuanto a qué se considera flora nasal normal. Recientemente, ha emergido Staphylococcus aureus meticilino resistente comunitario (MRSA-com) en personas sin factores de riesgo conocido, produciendo una alarma sanitaria a nivel mundial. Objetivo: Determinar la colonización nasal bacteriana y evaluar la presencia de MRSA-com. Material y método: Estudio prospectivo descriptivo, entre octubre de 2007 y octubre de 2008, en población sana. Se realizó toma de muestra de secreción nasal, incubación e identificación bacteriana por métodos convencionales. Resultados: Población estudiada con promedio de edad 37,6 +/-15,8 años, 55 por ciento de sexo femenino, y 37,1 por ciento tabaquismo activo. Se obtuvo 73 por ciento de cultivos positivos. Se identificaron 18 especies bacterianas, siendo las más frecuentes Staphylococcus coagulasa negativo (53 por ciento) y Staphylococcus aureus (22,7 por ciento). Se detectó sólo un caso de MRSA, cuyo análisis genético fue negativo para demostrar su origen comunitario. Discusión: Existe una alta tasa de portación nasal de S coagulasa negativo y S aureus, similar a lo reportado por la literatura internacional. Pese a que la prevalencia encontrada para S aureus es la habitual, no se encontraron muestras positivas a MRSA-com. Lo anterior indica que aún no existe en Chile la diseminación de clones de MRSA-com.

Introduction: Doesn't exists agreement about normal nasal flora. Recently it has emerged community-associated methicillin-resistant Staphylococcus aureus in people without known rísk factors, producing a global health scare. Aim: Look for normal nasal flora and test the presence oí MRSA-com. Material ana method: Descriptive and prospective study, between October 2007 and October 2008, in healthy people. Was taken a sampling from nasal secretion, incubation and bacterial identification by conventional methods. Results: Studied population, average age 37.6 +/-15.8years, 55 percent témale and 37.1 percent active smoking. We obtained 73 percent of positive cultures. We identified 18 bacterial species, the most common was Staphylococcus coagulase-negative (53 percent) and Staphylococcus aureus (22.7 percent). Was detected only one case ofMRSA, and his genetic test was negative to prove community origin. Discusión: There is a high rate of nasal carriage of Staphylococcus coagulase-negative, like to that reponed by international literature. Although the prevalence found for S aureus is the usual, there were no MRSA-com positive samples. This indicates that in Chile there is still no spread of clones of MRSA-com.

Size of internal jugular vs subclavian vein in small infants: an observational, anatomical evaluation with ultrasound.

BACKGROUND: The primary goal of this study was to compare the size and depth of the internal jugular vein (IJV) and the subclavian vein (SCV) in infants under general anaesthesia. A secondary goal was to determine the correlation of weight, height, head circumference, and age to the size and depth of these veins. METHODS: Sixty small infants weighing from 1.4 to 4.5 kg were included. Using ultrasound, the diameters via short-axis (SAX) and long-axis (LAX) views, cross-sectional area (CSA), and depth of the left and right IJV and SCV were measured. RESULTS: The diameter of the IJV was 7.9% larger on average than that of the SCV as measured via the SAX and LAX views (mean: 3.1 vs 2.9 mm; Wilcoxon's signed-rank test: P<0.01). The CSA of the IJV was 27% larger on average than that of the SCV (mean: 10.2 vs 8.0 mm(2); Wilcoxon's signed-rank test: P<0.01). Seventy-five per cent of the neonates showed a larger CSA of the IJV. The SCV was 8.4% deeper on average from the skin surface than the IJV (mean: 6.4 vs 5.9 mm; Wilcoxon's signed-rank test: P<0.01). There was a significant positive correlation between weight, height, head circumference, and age to the size and depth of the veins (Spearman's rank correlation: P<0.01). CONCLUSIONS: Because of its most likely larger size, the IJV can be recommended as the better choice for cannulation in comparison with the SCV. However, other factors should also be considered.