Social contact from birth influences personality traits of group-housed dairy calves.

The objective of this study was to assess effects of prior social contact on the expression of personality traits in group-housed calves. Holstein heifer and bull calves were housed in either individual pens (n = 16), or in pairs (n = 8 pairs) at birth before they were mingled between treatments and moved to group pens at approximately 2 wk of life (8 calves/pen). During wk 4 of life, calves were tested in a series of standardized behavioral tests: an open field test, a novel object test, an unfamiliar calf test, and an unfamiliar human test. Responses in the open field test and novel object test were analyzed using principal component analysis, yielding 2 factors interpreted as bold and inactive/grooming. Calves housed in pairs before grouping had greater scores for bold and tended to have lower scores for inactive/grooming. Responses in the unfamiliar calf and human tests were similarly analyzed, yielding 3 factors interpreted as calf-directed, active, and human-directed. Calves housed in pairs before grouping had lower scores for calf-directed, tended to have lower scores for active, and scores for human-directed did not differ. Following grouping, average daily gain, milk replacer intake, and meal frequency did not differ between previous housing treatments. Our results suggest that behavioral traits reflective of personality in group-housed calves may be influenced by social contact from birth even following adaptation to group-housing.

Expression pattern of MRPS18 family genes in gliomas.

AIM: To assess expression patterns of MRPS18 family genes in glioblastoma tissues and glioma cell lines. MATERIALS AND METHODS: Expression of MRPS18 family genes was analyzed by quantitative polymerase chain reaction in glioma cell lines and glioblastoma specimens. A bioinformatic analysis of the publicly available data on the expression of these genes was also provided. RESULTS: The genes of MRPS18 family show different expression patterns in glioblastomas and glioma cell lines. The highest levels of expression were found for MRPS18-2 at mRNA and protein levels in both glioblastomas and glioma cell lines; the lowest - for MRPS18-1 at mRNA level. CONCLUSIONS: The elevated levels of relative expression of the MRPS18-2 gene are characteristic for glioma tumor tissues and cell lines.

Is postspinal hypotension a sign of impaired cardiac performance in the elderly? An observational mechanistic study.

Background: We have previously reported that stroke volume is reduced in a majority of elderly patients undergoing surgical repair of hip fracture before and after intrathecal injection of anaesthetic. We aimed to investigate these observations further in a prospective study of elderly patients undergoing elective hip or knee arthroplasty under spinal anaesthesia. Methods: Patients ≥65 yr undergoing elective arthroplasty were monitored with LiDCOplus™ preoperatively (baseline), before and continuously for 45 min after spinal anaesthesia. Postspinal hypotension was defined as systolic blood pressure (bp) < 100 mm Hg or > 30% decrease from baseline. Associations between post-spinal hypotension and haemodynamic changes before (i.e. between baseline and before injection) spinal anaesthesia were analysed by logistic regression analysis. Results: Twenty patients with a mean age of 74 (range 66-89) yr were included. Stroke volume index decreased by 14% (95% CI 9.3%-19%) before spinal anaesthesia. When patients were categorised according to post-spinal hypotension (Y/N) the patterns of haemodynamic changes differed. In the hypotensive patients, cardiac index progressively decreased whereas it increased initially in the non-hypotensive patients. Reduction of cardiac index from baseline before spinal anaesthesia was associated with increased risk of hypotension: OR 0.79 (95% CI 0.60, 0.91). The predictive value of reduced cardiac index was good (AUC under ROC curve 0.91). Conclusions: A decrease in cardiac output from baseline before spinal anaesthesia and an inability to increase it after induction may be important features of postspinal hypotension in elderly patients.

Towards individualized perioperative, goal-directed haemodynamic algorithms for patients of advanced age: observations during a randomized controlled trial (NCT01141894).

BACKGROUND: During a previous study on intraoperative goal-directed haemodynamic treatment (GDHT) in elderly patients, cardiac performance did not improve as anticipated (ClinicalTrials.gov NCT01141894). We hypothesized that in this group, responsiveness to interventions could be predicted by individual patient characteristics. METHODS: Data for the present study were collected during a previously performed, single-centre, open, randomized, and controlled parallel-group superiority trial in patients aged ≥70 yr undergoing hip-fracture surgery. Haemodynamic parameters were collected by the LiDCOplus™ monitor. The GDHT group received oxygen delivery-guided fluid challenges and dobutamine infusion. Management in the routine fluid treatment group was clinician guided without access to LiDCOplus™ readings. In the GDHT group, independent predictors were assessed by multiple logistic regression analyses of two outcomes: first fluid challenge response (defined as increase of stroke volume by ≥10%); and overall intervention response (maintenance of oxygen delivery at the end of surgery). RESULTS: Data from 72 routine fluid treatment and 70 GDHT patients were analysed. Clinician-guided pre-anaesthesia fluid loading increased the stroke volume in 14% of patients, and 17% of patients increased or maintained oxygen delivery at the end of surgery. The GDHT-guided first and subsequent fluid challenges were associated with increased stroke volume in 39 and 9% of patients, respectively, and increased or maintained oxygen delivery was present in 47% of patients at the end of surgery. In the GDHT group, a baseline stroke volume index (<28 ml m(-2)) was an independent predictor of first fluid challenge response, and a baseline oxygen delivery index (<330 ml min(-1) m(-2)) was a predictor of maintained or increased oxygen delivery. CONCLUSIONS: Fewer patients responded to GDHT than anticipated. Our data suggest that individual characteristics could predict the haemodynamic responses. CLINICAL TRIAL REGISTRATION: NCT01141894.

Human dermal fibroblasts in psychiatry research.

In order to decipher the disease etiology, progression and treatment of multifactorial human brain diseases we utilize a host of different experimental models. Recently, patient-derived human dermal fibroblast (HDF) cultures have re-emerged as promising in vitro functional system for examining various cellular, molecular, metabolic and (patho)physiological states and traits of psychiatric disorders. HDF studies serve as a powerful complement to postmortem and animal studies, and often appear to be informative about the altered homeostasis in neural tissue. Studies of HDFs from patients with schizophrenia (SZ), depression, bipolar disorder (BD), autism, attention deficit and hyperactivity disorder and other psychiatric disorders have significantly advanced our understanding of these devastating diseases. These reports unequivocally prove that signal transduction, redox homeostasis, circadian rhythms and gene*environment (G*E) interactions are all amenable for assessment by the HDF model. Furthermore, the reported findings suggest that this underutilized patient biomaterial, combined with modern molecular biology techniques, may have both diagnostic and prognostic value, including prediction of response to therapeutic agents.

Fibroblasts from patients with major depressive disorder show distinct transcriptional response to metabolic stressors.

Major depressive disorder (MDD) is increasingly viewed as interplay of environmental stressors and genetic predisposition, and recent data suggest that the disease affects not only the brain, but the entire body. As a result, we aimed at determining whether patients with major depression have aberrant molecular responses to stress in peripheral tissues. We examined the effects of two metabolic stressors, galactose (GAL) or reduced lipids (RL), on the transcriptome and miRNome of human fibroblasts from 16 pairs of patients with MDD and matched healthy controls (CNTR). Our results demonstrate that both MDD and CNTR fibroblasts had a robust molecular response to GAL and RL challenges. Most importantly, a significant part (messenger RNAs (mRNAs): 26-33%; microRNAs (miRNAs): 81-90%) of the molecular response was only observed in MDD, but not in CNTR fibroblasts. The applied metabolic challenges uncovered mRNA and miRNA signatures, identifying responses to each stressor characteristic for the MDD fibroblasts. The distinct responses of MDD fibroblasts to GAL and RL revealed an aberrant engagement of molecular pathways, such as apoptosis, regulation of cell cycle, cell migration, metabolic control and energy production. In conclusion, the metabolic challenges evoked by GAL or RL in dermal fibroblasts exposed adaptive dysfunctions on mRNA and miRNA levels that are characteristic for MDD. This finding underscores the need to challenge biological systems to bring out disease-specific deficits, which otherwise might remain hidden under resting conditions.

Stevens-Johnson Syndrome triggered by a combination of clobazam, lamotrigine and valproic acid in a 7-year-old child.

Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are diseases within the spectrum of severe cutaneous adverse reactions affecting skin and mucous membranes. Antiepileptic drugs (AEDs) are used in combination, leading to potential pharmacokinetic or pharmacodynamic interactions, causing more adverse effects than might occur when the AED is taken as monotherapy. Here, we report a rare case of SJS triggered by a combination of clobazam, lamotrigine and valproic acid in a 7-year-old boy. Because of inadequate seizure control, lorazepam was replaced with clobazam. Four weeks after the addition of clobazam, the patient developed SJS with a generalized rash, fever, with liver and kidney involvement, and eosinophilia one week after the initiation of treatment. All antiepileptic drugs were discontinued, and intravenous methylprednisolone, prophylactic systemic antibiotics, intravenous fluid supplement, antipyretic, special wound care, and supportive medical care for SJS were administered. He was discharged in a stable condition on the 18th day. Our case suggests that a drug-drug interaction between valproate, lamotrigine and clobazam contributed to the development of SJS. When the clobazam was added to valproic acid and lamotrigine co-medication, the lamotrigine dose should have been decreased.

La syndrome de Stevens-Johnson (SJS) et la nécrolyse épidermique toxique sont des maladies dans le spectre de réactions cutanées graves affectant la peau et les muqueuses. Les médicaments antiépileptiques sont utilisés en combinaison, et ceci peut provoquer des effets indésirables. Ici, nous rapportons un cas rare de SJS déclenché par une combinaison de clobazam, la lamotrigine et l'acide valproïque chez un garçon de 7 ans. En raison de l' insuffisante maîtrise des crises, le lorazépam a été utilisé avec le clobazam. Quatre semaines après l'ajout de clobazam, le patient a développé SJS avec une éruption cutanée généralisée, de la fièvre. Il y avait la participation de la foie et les reins, et une éosinophilie, une semaine après le début du traitement. Tous les médicaments antiépileptiques ont été abandonnées, et la méthylprednisolone intraveineuse, des antibiotiques systémiques prophylactiques, supplément de liquide par voie intraveineuse, antipyrétique, les soins des plaies spécial, et de soutien pour les soins médicaux ont été administrés. Il a été libéré dans un état stable la 18ème journée. Notre cas suggère qu'une interaction médicamenteuse entre le valproate, la lamotrigine et clobazam ait contribué au développement de SJS. Lorsque le clobazam a été ajouté à l'acide valproïque et la lamotrigine, la dose de lamotrigine aurait dû être diminué.

Randomized controlled trial of goal-directed haemodynamic treatment in patients with proximal femoral fracture.

BACKGROUND: Patients with proximal femoral fracture (PFF) are at high risk of postoperative complications. Goal-directed haemodynamic treatment (GDHT) in other high-risk surgical patients reduces postoperative complications. We aimed to compare effects of GDHT and routine fluid treatment (RFT) on postoperative outcomes after PFF surgery. METHODS: PFF patients (≥70 yr) were enrolled in this single-centre, open, randomized, controlled, parallel-group superiority trial with concealed allocation using computer-generated randomization. TREATMENTS: (i) GDHT to attain oxygen delivery index >600 ml min(-1) m(-2) using fluids and dobutamine and (ii) a protocol-guided RFT. After 150 enrolled patients, the trial was stopped due to slow recruitment. The short-term primary outcome measure was the relative risk (RR) of postoperative complications; secondary measures were (i) administered fluid levels, (ii) vasopressor requirements, and (iii) haemodynamic responses. RESULTS: For the GDHT group, 74 and for the RFT group 75 patients were designated. The RR of postoperative complications (GDHT vs RFT) was 0.79 (95% confidence interval 0.54-1.16); the volumes of i.v. fluids decreased (1078 vs 1440 ml, P=0.01); fewer patients required treatment of hypotension (18.5% vs 75%, P<0.005); there were more patients with increased oxygen delivery at the end of operation (28% vs 8%, P=0.04), but the haemodynamic goal was achieved in only 27% of patients in the GDHT group. CONCLUSIONS: The magnitude of risk reduction of postoperative complications is clinically relevant, but the trial was underpowered and the null hypothesis cannot be rejected.

Effects of maternal immune activation on gene expression patterns in the fetal brain.

We are exploring the mechanisms underlying how maternal infection increases the risk for schizophrenia and autism in the offspring. Several mouse models of maternal immune activation (MIA) were used to examine the immediate effects of MIA induced by influenza virus, poly(I:C) and interleukin IL-6 on the fetal brain transcriptome. Our results indicate that all three MIA treatments lead to strong and common gene expression changes in the embryonic brain. Most notably, there is an acute and transient upregulation of the α, ß and γ crystallin gene family. Furthermore, levels of crystallin gene expression are correlated with the severity of MIA as assessed by placental weight. The overall gene expression changes suggest that the response to MIA is a neuroprotective attempt by the developing brain to counteract environmental stress, but at a cost of disrupting typical neuronal differentiation and axonal growth. We propose that this cascade of events might parallel the mechanisms by which environmental insults contribute to the risk of neurodevelopmental disorders such as schizophrenia and autism.

Gut microcirculatory and mitochondrial effects of hyperdynamic endotoxaemic shock and norepinephrine treatment.

BACKGROUND: Microcirculatory and mitochondrial dysfunction are important factors in the development of septic shock. In this study, we investigated the effects of fluid resuscitated endotoxaemic shock and norepinephrine treatment on intestinal microcirculation and mitochondrial function in sheep. METHODS: Eight anaesthetized sheep received an i.v. infusion of endotoxin. After 24 h, mean arterial pressure (MAP) was restored to baseline levels with a norepinephrine infusion. Five sheep served as sham experiments. Central and regional haemodynamics were monitored, and ileal microcirculation was evaluated with laser Doppler and sidestream dark-field videomicroscopy techniques. Gut mucosal acidosis was assessed by air tonometry, and ileal wall biopsies were analysed for mitochondrial activity. RESULTS: After 24 h of endotoxaemia, the animals had developed hyperdynamic shock with systemic and mucosal acidosis. Although superior mesenteric artery (SMA) flow was higher than the baseline values, ileal microcirculatory perfusion and mitochondrial complex I activity decreased. After norepinephrine was started, SMA flow, ileal microcirculation, and mucosal acidosis remained unchanged. Although no statistically significant difference could be demonstrated, norepinephrine increased mitochondrial complex I activity in five of the six animals from which ileal biopsies were taken. CONCLUSIONS: Although fluid resuscitated endotoxaemic shock increased regional blood flow, microcirculatory and mitochondrial alterations were still present. Restoring MAP with norepinephrine did not affect ileal microcirculation or mucosal acidosis, indicating that perfusion pressure manipulation is of limited importance to the intestinal microcirculation in established endotoxaemic shock.

Shaping the future of Scandinavian anaesthesiology: a position paper by the SSAI.

Traditionally, Scandinavian anaesthesiologists have had a very broad scope of practice, involving intensive care, pain and emergency medicine. European changes in the different medical fields and the constant reorganising of health care may alter this. Therefore, the Board of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) decided to produce a Position Paper on the future of the speciality in Scandinavia. The training in the various Scandinavian countries is very similar and provides a stable foundation for the speciality. The Scandinavian practice in anaesthesia and intensive care is based on a team model where the anaesthesiologists work together with highly educated nurses and should remain like this. However, SSAI thinks that the role of the anaesthesiologists as perioperative physicians is not fully developed. There is an obvious need and desire for further training of specialists. The SSAI advanced educational programmes for specialists should be expanded and include formal assessment leading to a particular medical competency as defined by the European Union of Medical Specialists (UEMS). In this way, Scandinavian anaesthesiologists will remain leaders in perioperative, intensive care, pain and critical emergency medicine.

Could benefits of epidural analgesia following oesophagectomy be measured by perceived perioperative patient workload?

BACKGROUND: A controversy exists whether beneficial analgesic effects of epidural analgesia over intravenous analgesia influence the rate of post-operative complications and the length of hospital stay. There is some evidence that favours epidural analgesia following major surgery in high-risk patients. However, there is a controversy as to whether epidural analgesia reduces the intensive care resources following major surgery. In this study, we aimed at comparing the post-operative costs of intensive care in patients receiving epidural or intravenous analgesia. METHODS: Clinical data and rates of post-operative complications were extracted from a previously reported trial following thoraco-abdominal oesophagectomy. Cost data for individual patients included in that trial were retrospectively obtained from administrative records. Two separate phases were defined: costs of pain treatment and the direct cost of intensive care. RESULTS: Higher calculated costs of epidural vs. intravenous pain treatment, 1,037 vs. 410 Euros / patient, were outweighed by lower post-operative costs of intensive care 5,571 vs. 7,921 Euros / patient (NS). CONCLUSION: Higher costs and better analgesic effects of epidural analgesia compared with intravenous analgesia do not reduce total costs for post-operative care following major surgery.

Idiopathic infantile hypercalcemia and renal involvement.

Idiopathic infantile hypercalcemia is recognized as a rare cause of infantile hypercalcemia. Its renal consequences include nephrocalcinosis with distal tubular dysfunction, nephrolithiasis, and finally renal failure. Herein we report the case of a two-month-old infant presenting with idiopathic infantile hypercalcemia complicated with distal renal tubular acidosis (RTA) and nephrocalcinosis. Despite correction of acidosis and dehydration, the persistant hypercalcemia could only be ameliorated with calcitonin treatment. Early diagnosis and appropriate treatment is life-saving in such cases.

Combined photoplethysmographic monitoring of respiration rate and pulse: a comparison between different measurement sites in spontaneously breathing subjects.

BACKGROUND: The non-invasive photoplethysmographic (PPG) signal reflects blood flow and volume in a tissue. The PPG signal shows variation synchronous with heartbeat (PPGc), as used in pulse oximetry, and variations synchronous with breathing (PPGr). PPGr has been used for non-invasive monitoring of respiration with promising results. Our aim was to investigate PPG signals recorded from different skin sites in order to find suitable locations for parallel monitoring of variations synchronous with heartbeat and breathing. METHODS: PPG sensors were applied to the forearm, finger, forehead, wrist and shoulder on 48 awake healthy volunteers. From these sites, seven PPG signals were simultaneously recorded during normal spontaneous breathing over 10 min. Capnometry served as respiration and electrocardiogram (ECG) as pulse reference signals. PPG signals were compared with respect to power spectral content and squared coherence. RESULTS: Forearm PPG measurement showed significantly higher power within the respiratory region of the power spectrum [median (quartile range) 42 (26)%], but significantly lower power within the cardiac region [9 (10)%] compared with the other skin sites. PPG finger measurement showed the opposite; in transmission mode, the power within the respiratory region was significantly lower [4 (10)%] and within the cardiac region significantly higher [45 (25)%] than the other sites. PPGc coherence values were generally high [>0.96 (0.08)], and PPGr coherence values lower [0.83 (0.35)-0.94 (0.17)]. CONCLUSION: Combined PPG respiration and pulse monitoring is possible, but there are significant differences between the respiratory and cardiac components of the PPG signal at different sites.

Effect of sevoflurane on cerebral blood flow and cerebrovascular resistance at surgical level of anaesthesia: a transcranial Doppler study.

BACKGROUND AND OBJECTIVE: It is widely accepted that sevoflurane affects cerebral circulation, but there are uncertainities regarding the magnitude of its effect. The aim of the present work was to assess the effect of sevoflurane on the cerebral circulation at surgical levels of anaesthesia. METHODS: Twenty patients undergoing elective lumbar discectomies were investigated. Anaesthesia was induced with propofol and maintained with sevoflurane. The level of surgical anaesthesia was determined by bispectral index, the target level was 45-55. Transcranial Doppler (TCD) measurement was performed before induction and after reaching the surgical level of anaesthesia. Besides routine parameters (middle cerebral artery mean blood flow velocity (MCAV) and pulsatility index (PI)) derived parameters (estimated cerebral perfusion pressure (eCPP), cerebral blood flow index (CBFI) and resistance area product (RAP)) were calculated by taking changes of mean arterial pressure also into account. RESULTS: MCAV decreased from 54.1 +/- 13.3 to 43.7 +/- 18.5 cm s-1, P < 0.01 and PI increased from 0.79 +/- 0.2 to 0.92 +/- 0.2, P < 0.01 after reaching the surgical level of anaesthesia. As a result eCPP decreased by 18.2%, CBFI by 25.5% and RAP increased by 15% respectively. CONCLUSIONS: Our data indicate a vasodilatory effect of sevoflurane at surgical level of anaesthesia on large cerebral vessels or a vasoconstriction of the resistance arterioles likely caused by decreased brain metabolism.

Evaluation of costs and effects of epidural analgesia and patient-controlled intravenous analgesia after major abdominal surgery.

BACKGROUND: The outcome of different treatment strategies for postoperative pain has been an issue of controversy. Apart from efficacy and effectiveness a policy decision should also consider cost-effectiveness. Since economic analyses on postoperative pain treatment are rare we developed a decision model in a pilot cost-effectiveness analysis (CEA) comparing epidural analgesia (EDA) and patient-controlled intravenous analgesia (PCIA) after major abdominal surgery in routine care. METHODS: Using a decision-tree model, treatment with EDA (ropivacaine and morphine) was compared with PCIA (morphine). Effects and costs of treatment were established. The number of pain-free days at rest (pain intensity <30 using visual analogue scale 1-100 mm) was the primary measure of effect. An incremental cost-effectiveness ratio (ICER) was calculated as the difference in direct costs divided by the difference in effect. A database on 644 patients collected for the purpose of quality control during the period of 1997 to 1999 was the main data source. Sensitivity analysis was used to test uncertain data. RESULTS: EDA was more effective in terms of pain-free days but more expensive. The additional cost for each pain-free day was 5652 Euros. CONCLUSION: It is a judgement of value if the additional cost is reasonable. When the cost of around 55,000 Euros per gained life-year with full health for other interventions is debated, our result indicates poor cost-effectiveness for EDA. Before any conclusion can be drawn concerning policy recommendations the difference in costs has to be related to other outcome measures as length of hospital stay, morbidity and mortality are required.

Hepatitis B complicated focal segmental glomerulosclerosis.

After the initial report of membranous glomerulopathy due to hepatitis B virus infection by Combes et al, other glomerular diseases - but rarely focal segmental glomerulosclerosis (FSGS) association with HBV infection - have been reported. Herein we present an 8-year-old boy with chronic HBV infection complicated FSGS. The patient was initially regarded as idiopathic FSGS and started on an immunosuppressive schedule. The elevation of liver transaminases in the course of the therapy revealed the immunotolerated perinatal HBV infection. It was considered that immunosuppressive agents have induced viral replication. The treatment was changed to lamivudine alone. The nephrotic syndrome has already been improved with the seroconversion of anti-HBeAg and reduced liver functional tests by the tenth month of the treatment. This case is peculiar for the seldom association of FSGS with chronic HBV infection and treatment modality particularly for the countries where this viral infection is endemic.