Transverse tripolar stimulation for selective FNS

Various anode-cathode configurations in a nerve cuff were modeled in order to optimize its spatial selectivity characteristics for FNS. Apart from the usual configurations (monopole, bipole, longitudinal tripole, ¿steering¿ anode), a transverse tripolar configuration (central cathode) was examined. The model predictions were verified by acute animal experiments. It is concluded that a transverse tripole activates superficial nerve fibers in a more selective way than other configurations d

Transverse tripolar stimulation of peripheral nerve:A modelling study of spatial selectivity

Various anode-cathode configurations in a nerve cuff are modelled to predict their spatial selectivity characteristics for functional nerve stimulation. A 3D volume conductor model of a monofascicular nerve is used for the computation of stimulation-induced field potentials, whereas a cable model of myelinated nerve fibre is used for the calculation of the excitation thresholds of fibres. As well as the usual configurations (monopole, bipole, longitudinal tripole, ‘steering’ anode), a transverse tripolar configuration (central cathode) is examined. It is found that the transverse tripole is the only configuration giving convex recruitment contours and therefore maximises activation selectivity for a small (cylindrical) bundle of fibres in the periphery of a monofascicular nerve trunk. As the electrode configuration is changed to achieve greater selectivity, the threshold current increases. Therefore threshold currents for fibre excitation with a transverse tripole are relatively high. Inverse recruitment is less extreme than for the other configurations. The influences of several geometrical parameters and model conductivities of the transverse tripole on selectivity and threshold current are analysed. In chronic implantation, when electrodes are encapsulated by a layer of fibrous tissue, threshold currents are low, whereas the shape of the recruitment contours in transverse tripolar stimulation does not change

Adults with corrected oesophageal atresia: is oesophageal function associated with complaints and/or quality of life?

The aim of this study was to evaluate oesophageal function after correction of oesophageal atresia in adults, and to investigate the association between complaints, oesophageal function and quality of life (QoL). Twenty-five adults were included who participated in previous follow-up studies, during which complaints of dysphagia and gastro-oesophageal reflux (GOR), results of upper gastrointestinal endoscopy, oesophageal biopsies and QoL had been collected. Manometry was performed in 20 patients, 24 h pH-measurements were performed in 21 patients. pH-values (sample time 5 s) were calculated using criteria of Johnson and DeMeester. Associations were tested with ANOVA and χ2-tests. Ten patients (48%) reported complaints of dysphagia, seven (33%) of GOR. The amplitude of oesophageal contractions was low (<15 mmHg) in four patients (20%). pH-measurements showed pathological reflux in three patients (14%). Patients reporting dysphagia more often had disturbed motility (P = 0.011), and lower scores on the domains “general health perceptions” (SF-36) (P = 0.026), “standardised physical component” (SF-36) (P = 0.013), and “physical well-being” (GIQLI) (0.047). No other associations were found. This study shows a high percentage of oesophageal motility disturbances and a moderate percentage of GOR after correction of oesophageal atresia. Patients reporting dysphagia, whom more often had disturbed motility, seemed to be affected by these symptoms in their QoL

Body mass index affects kidney transplant outcomes: a cohort study over 5 years using a steroid sparing protocol

Background: There is controversy regarding the suitability of high body mass index (BMI) candidates accessing the transplant waitlist. Patients and Methods: Observational study on consecutive kidney transplant recipients undergoing surgery between January 2014 and March 2016 at our centre. Patients were stratified according to BMI. Survival outcomes and graft function were analysed to In review investigate the effect of donor’s and recipient’s demographic characteristics. Results: 396 kidney transplant recipients: 260 males, mean age 51.8 ± 15.9 years, followed up for a mean time of 5.86 ± 2.29 years. Mean BMI 26.2 ± 5.1. BMI class 1 (20 ≤ BMI ≤ 24.9) n=133, class 2 (25 ≤ BMI ≤ 29.9) n= 155, class 3 (30 ≤ BMI ≤34.9) n=53, class 4 (BMI ≥ 35) n=21), class V (BMI ≤ 19.9) n=34. Patient survival was not significantly different according to the recipient’s BMI class (p=0.476); graft survival was affected (p=0.031), as well as graft function up to 2 years post-transplant and at 4 years follow up (p=0.016). At logistic regression the factors independently associated with graft loss were only donor’s age (p=0.05) and BMI class of the recipient (p=0.002). Conclusions: Obesity did not impact on patient’s survival but affected graft function and graft loss

Another face of Lorenz-Mie scattering: monodisperse distributions of spheres produce Lissajous-like patterns

The complete scattering matrix S of spheres was measured with a flow cytometer. The experimental equipment allows simultaneous detection of two scattering-matrix elements for every sphere in the distribution. Two-parameter scatterplots withx andy coordinates determined by the Sll + Sij and S11 - Sij values are measured. Samples of spheres with very narrow size distributions (< 1%) were analyzed with a FlowCytometer, and they produced unexpected two-parameter scatterplots. Instead of compact distributions we observed Lissajous-like loops. Simulation of the scatterplots, using Lorenz-Mie theory, shows that these loops are due not to experimental errors but to true Lorenz-Mie scattering. It is shown that the loops originate from the sensitivity of the scattered field on the radius of the spheres. This paper demonstrates that the interpretation of rare events and hidden features in flow cytometry needs reconsideration

The role of T-cell co-stimulatory molecules in murine models of allergic asthma

Summary The role of T-cell co-stimulatory molecules in murine models of allergic asthma. Allergen-specific T helper type 2 (Th2) cells play a pivotal role in the pathogenesis and progression of allergic asthma by orchestrating the inflammatory response. For optimal activation, T-cells require nonspecific co-stimulatory signals in addition to the antigen-specific signal conferred by the T-cell receptor. In this thesis, the role and therapeutic potential of blockade of T-cell co-stimulation in ovalbumin (OVA)-induced murine models of allergic asthma were investigated. The main co-stimulatory receptor on T-cells is CD28. Two ligands are available for this receptor: B7-1 and B7-2. The second receptor for the B7 ligands, CTLA4, is expressed on activated T-cells and delivers an inhibitory signal to terminate the immune response. The existence of a third B7-1/B7-2 receptor was postulated in a recent study using a novel mouse strain lacking both CD28 and CTLA4 (CD28/CTLA4?/?). However, no manifestations of allergic asthma could be induced by OVA in both CD28/CTLA4?/? and B7-1/B7-2?/? mice. So, whereas T-cell co-stimulation via the putative B7-1/B7-2 receptor appears to play no role in the development of asthma manifestations in this murine model, CD28 signaling is critical. However, asthma patients start therapy after the development of airway symptoms while exposure to environmental allergen mostly continues. Therefore, it was investigated if blockade of CD28 can reverse established manifestations of allergic asthma in mice after the development of these manifestations while OVA exposures are continued (ongoing murine model of allergic asthma) (chapter 3). Blockade of CD28 substantially inhibited the established antigen-induced airway manifestations in mice. In a more severe ongoing model induced by a different OVA sensitization- and challenge protocol, the effects of CD28 blockade on established asthma manifestations were less pronounced. The recently discovered, CD28-family member, inducible T-cell co-stimulator (ICOS) has been suggested to play a more prominent role in the effector phase rather than in the initiation of the Th2-dominated allergic inflammatory response. However, blockade of ICOS appeared to have no effect on any of the established manifestations in the ongoing murine model of allergic asthma whereas blockade during the development of these manifestations was much less effective compared with blockade of CD28 (chapter 4). Blockade of T-cell co-stimulation has been shown not only to result in the immediate suppression of the immune response but to induce in some disease models long-term antigen-specific unresponsiveness (tolerance) as well. Short-lived treatment that induces selective tolerance to the inhalant allergen would be a very attractive therapeutic approach for allergic asthma. Therefore, it was investigated if blockade of T-cell co-stimulation during the development of asthma manifestations also had an effect after serum clearance when mice were re-challenged with OVA (chapter 5). Blockade of the CD28:B7 pathway -but not of the CD40 ligand:CD40 pathway (another well-known pathway of T-cell co-stimulation)- could induce tolerance for some asthma manifestations re-induced by OVA re-challenge. So, these pre-clinical studies indicate that blockade of T-cell co-stimulation, especially the CD28:B7 interaction, may be an alternative therapy for both asthma patients in clinical remission and those with ongoing disease. The latter group possibly requiring additional therapy