Ultrasound-guided lumbar plexus block in volunteers; a randomized controlled trial.

Background: The currently best-established ultrasound-guided lumbar plexus block (LPB) techniques use a paravertebral location of the probe, such as the lumbar ultrasound trident (LUT). However, paravertebral ultrasound scanning can provide inadequate sonographic visibility of the lumbar plexus in some patients. The ultrasound-guided shamrock LPB technique allows real-time sonographic viewing of the lumbar plexus, various anatomical landmarks, advancement of the needle, and spread of local anaesthetic injectate in most patients. We aimed to compare block procedure outcomes, effectiveness, and safety of the shamrock vs LUT. Methods: Twenty healthy men underwent ultrasound-guided shamrock and LUT LPBs (2% lidocaine­adrenaline 20 ml, with 1 ml diluted contrast added) in a blinded randomized crossover study. The primary outcome was block procedure time. Secondary outcomes were procedural discomfort, number of needle insertions, injectate spread assessed with magnetic resonance imaging, sensorimotor effects, and lidocaine pharmacokinetics. Results: The shamrock LPB procedure was faster than LUT (238 [sd 74] vs 334 [156] s; P=0.009), more comfortable {numeric rating scale 0­10: 3 [interquartile range (IQR) 2­4] vs 4 [3­6]; P=0.03}, and required fewer needle insertions (2 [IQR 1­3] vs 6 [2­12]; P=0.003). Perineural injectate spread seen with magnetic resonance imaging was similar between the groups and consistent with motor and sensory mapping. Zero/20 (0%) and 1/19 (5%) subjects had epidural spread after shamrock and LUT (P=1.00), respectively. The lidocaine pharmacokinetics were similar between the groups. Conclusions: Shamrock was faster, more comfortable, and equally effective compared with LUT. Clinical trial registration: NCT02255591

The suprasacral parallel shift vs lumbar plexus blockade with ultrasound guidance in healthy volunteers--a randomised controlled trial.

Surgical anaesthesia with haemodynamic stability and opioid-free analgesia in fragile patients can theoretically be provided with lumbosacral plexus blockade. We compared a novel ultrasound-guided suprasacral technique for blockade of the lumbar plexus and the lumbosacral trunk with ultrasound-guided blockade of the lumbar plexus. The objective was to investigate whether the suprasacral technique is equally effective for anaesthesia of the terminal lumbar plexus nerves compared with a lumbar plexus block, and more effective for anaesthesia of the lumbosacral trunk. Twenty volunteers were included in a randomised crossover trial comparing the new suprasacral with a lumbar plexus block. The primary outcome was sensory dermatome anaesthesia of L2-S1. Secondary outcomes were peri-neural analgesic spread estimated with magnetic resonance imaging, sensory blockade of dermatomes L2-S3, motor blockade, volunteer discomfort, arterial blood pressure change, block performance time, lidocaine pharmacokinetics and complications. Only one volunteer in the suprasacral group had sensory blockade of all dermatomes L2-S1. Epidural spread was verified by magnetic resonance imaging in seven of the 34 trials (two suprasacral and five lumbar plexus blocks). Success rates of the sensory and motor blockade were 88-100% for the major lumbar plexus nerves with the suprasacral technique, and 59-88% with the lumbar plexus block (p > 0.05). Success rate of motor blockade was 50% for the lumbosacral trunk with the suprasacral technique and zero with the lumbar plexus block (p < 0.05). Both techniques are effective for blockade of the terminal nerves of the lumbar plexus. The suprasacral parallel shift technique is 50% effective for blockade of the lumbosacral trunk.

Measurement of nitric oxide and 8-isoprostane in exhaled breath of children with atopic eczema.

BACKGROUND: Children with atopic eczema (AE) are at risk of developing asthma. Airway inflammation has been shown to be present before the onset of clinical asthma. Increased exhalation (forced expiration; FE) of nitric oxide (FE(NO)) and 8-isoprostane seems to be a feature of bronchial inflammation in people with asthma. AIM: To determine whether the exhalation of these two molecules is increased in children with eczema, even in the absence of overt asthma. METHODS: In total, 21 children with AE were recruited and compared with healthy controls. A questionnaire was completed to identify respiratory symptoms compatible with asthma. The severity of AE was graded clinically. Spirometry, FE(NO) measurements and exhaled breath condensate collection for 8-isoprostane were performed. RESULTS: The mean level of 8-isoprostane was similar for children with AE (2.33 +/- 4.76 pg/mL) and controls (3.37 +/- 3.43). FE(NO) was increased in children with AE (mean 64.97 parts per billion) compared with the normal range, even in the absence of respiratory symptoms and in the presence of normal lung function. CONCLUSIONS: FE(NO) but not 8-isoprostane levels in exhaled breath condensate are higher in children with AE without asthma. Our finding may indicate a predictive role for FE(NO) for the development of asthma.

Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization.

BACKGROUND: Food allergies are an important cause of life-threatening hypersensitivity reactions. Oral tolerance can be considered the default immune response to dietary antigens, with immune deviation resulting in allergic sensitization. However, primary sensitization to food allergens may not solely be through the gastrointestinal mucosa, as strong T-helper type 2 (Th2)-biased immunity can result from exposure to protein allergens on barrier-disrupted skin. OBJECTIVE: The purpose of this study was to examine whether exposure to allergens through the skin may interfere with the normal development of oral tolerance and promote allergic sensitization to food proteins. METHODS: Female BALB/c mice were exposed epicutaneously to peanut protein and induction of systemic oral tolerance through high dose feeds of peanut protein was subsequently assessed. Other mice were rendered tolerant prior to epicutaneous peanut exposure. Sensitivity to peanut was determined by assessing delayed-type hypersensitivity, proliferative, cytokine and antibody responses. RESULTS: Epicutaneous exposure to peanut protein induced potent Th2-type immunity with high levels of IL-4 and serum IgE. Primary skin exposure prevented the subsequent induction of oral tolerance to peanut in an antigen-specific manner. Upon oral challenge, mice became further sensitized and developed strong peanut-specific IL-4 and IgE responses. Furthermore, animals with existing tolerance to peanut were partly sensitized following epicutaneous exposure. CONCLUSION: Epicutaneous exposure to peanut protein can prevent induction of oral tolerance, and may even modify existing tolerance to peanut. Epidermal exposure to protein allergens selectively drives Th2-type responses, and as such may promote sensitization to food proteins upon gastrointestinal exposure.

A defect in bone marrow derived dendritic cell maturation in the nonobesediabetic mouse.

The pathogenesis of diabetes in the nonobese diabetic (NOD) mouse is characterized by a selective destruction of the insulin-producing beta-cells in the islets of Langerhans mediated by autoreactive T cells. The function of T cells is controlled by dendritic cells (DC), which are not only the most potent activators of naïve T cells, but also contribute significantly to the establishment of central and peripheral tolerance. In this study, we demonstrate that the NOD mouse (H2: K(d), Ag(7), E*, D(b)) shows selective phenotypic and functional abnormalities in DC derived from bone marrow progeny cells in response to GM-CSF (DC(NOD)). NOD DC, in contrast to CBA DC, have very low levels of intracellular I-A molecules and cell surface expression of MHC class II, CD80, CD86 and CD40 but normal beta 2-microglobulin expression. Incubation with the strong inflammatory stimulus of LPS and IFN-gamma does not increase class II MHC, CD80 or CD86, but upregulates the level of CD40. The genetic defect observed in the DC(NOD) does not map to the MHC, because the DC from the MHC congenic NOD.H2(h4) mouse (H2: K(k), A(k), E(k), D(k)) shares the cell surface phenotype of the DC(NOD). DC from these NOD.H2(h4) also fail to present HEL or the appropriate HEL-peptide to an antigen-specific T cell hybridoma. However all the DC irrespective of origin were able to produce TNF-alpha, IL-6, low levels of IL-12(p70) and NO in response to LPS plus IFN-gamma. A gene or genes specific to the NOD strain, but outside the MHC region, therefore must regulate the differentiation of DC in response to GM-CSF. This defect may contribute to the complex genetic aetiology of the multifactorial autoimmune phenotype of the NOD strain.

Is lack of peripheral tolerance induction a cause for diabetes in the non-obese diabetic mouse?

The non-obese diabetic (NOD) mouse is a spontaneous animal model for type 1 diabetes characterized by a selective destruction of the insulin producing beta cells in the pancreas. As in humans, the disease is controlled by several susceptibility genes, some of which map to the major histocompatibility complex on chromosome 17. However, environmental factors also contribute to the development of the disease in the NOD mouse, presumably through controlling the balance between the Th1 and Th2 response in the animal. Recent observations have shown that the NOD mouse has abnormalities in the development of bone marrow-derived antigen-presenting cells. These include the most potent activators of naive T cells, the dendritic cells, which exist in at least two different sub-populations; DC1 cells, responsible for activation of Th1 cells, and DC2 cells, which produce Th2 cells. In addition to activating naive T cells, the dendritic cells are also involved in generating central and peripheral tolerance to self molecules. In this process DC2 cells appear to be more important for the development of peripheral tolerance than DC1 cells. Besides abnormalities in the development of bone marrow-derived antigen-presenting cells, the NOD mouse also has a defect in the thymic selection of T cells, leading to a higher concentration of autoreactive T cells. We speculate that the NOD mouse may develop an imbalance in the two subsets of dendritic cells with a skewing towards DC cells, thus having a reduced ability to generate peripheral tolerance to a number of autoantigens.