A Preliminary Feasibility Study of Different Implantable Pulse Generators Technologies for Diaphragm Pacing System

Diaphragm pacing stimulation (DPS) for ventilator‐dependent patients provides several advantages over conventional techniques such as phrenic nerve pacing or mechanical ventilator support. To date, the only existing system for DPS uses lead electrodes, percutaneously attached to an external pulse generator (PG). However, for a widespread use of this technique it would be more appropriate to eliminate the need for percutaneous wire and use a totally implantable system. The aim of this study was to determine if it were feasible to replace the external PG by an implantable system. We present here the results of a preliminary study of two different PG, currently used in other electrical stimulation (ES) clinical applications, which could be used as implantable DPS systems. One radio‐frequency‐powered PG, one rechargeable battery‐powered PG, and the current external PG were tested. Each was attached to the externalized part of the wires, connected to the diaphragm and tidal volume (TV) was measured in one ventilator‐dependent patient who has been using the current percutaneous stimulator for 3 years. Results indicated that both implantable PGs could achieve equivalent ventilatory requirements to the current external stimulator. No significant differences were observed between the three PG systems when stimulating the electrodes as used in the patient's own chronically attached PG system. We found that TV increased with increases in charge and frequency as expected when stimulating the patient's electrodes individually and in combination with each PG system. These results are a significant step toward developing a totally implantable DPS system for the ventilator‐dependant patients. Further clinical tests to demonstrate the safety and efficacy of a fully implanted DPS system are warranted.     

Induction of high levels of IgG autoantibodies in mice infected with Plasmodium chabaudi

This study analyzed the effect of infection of mice with a virulent strain of Plasmodium chabaudi on natural autoantibodies. Mice received appropriate treatments in order to survive and the serum autoantibodies were characterized either by enzyme immunoassays against a panel of self and non-self antigens or by Western immunoblots using fibroblast or red blood cell (RBC) extracts. IgM and mainly IgG antibodies directed against actin, myoglobin, myosin, spectrin, tubulin, and trinitrophenylated-ovalbumin were found a few days after the parasitemia peak, persisted for several weeks after parasite clearance, and returned to almost normal levels after 2 months. Following a challenge with parasitized RBCs, a similar increase in all antibodies was observed, their levels remaining high 20 days post-injection and still remaining at twice the normal level 1 month later. Western blotting detected autoantibodies to many membrane RBC proteins, e.g. spectrin, and band 3 and its related polypeptides, as well as against fibroblast constituents, such as tubulin, actin, and the 70 kd heat shock protein. Autoantibodies seemed to be polyspecific, since those eluted from infected mouse RBCs and the IgG antibodies from infected mouse sera affinity-purified on a mouse tubulin immunoadsorbent reacted with all antigens of the panel, including parasite extracts. Surprisingly, in mice which had recovered from infection, autoantibody levels, particularly anti-spectrin and anti-band 3, rose after the injection of a high dose of normal instead of parasitized RBCs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of ex-vivo PAF-induced platelet aggregation by the PAF-antagonist RP 48740: relationship to plasma concentrations in healthy volunteers

Summary RP 48740, 3-(3-pyridyl)-1H,3H-pyrrolo [1,2-c] thiazole-7-carboxamide, a specific competitive PAF-receptor antagonist in vitro, was given to 29 healthy male volunteers for 7 days. Plasma drug concentrations and exvivo PAF-induced platelet aggregation were assessed on Days 1, 4, and 7.RP 48740 had linear pharmacokinetics after single and repeated doses. It caused stable inhibition of PAF-induced platelet aggregation in a dose-dependent manner. The effect disappeared within 24 h, even after 7 days of repeated doses.The effect of RP 48740 displayed a sigmoidal relation to the plasma drug concentration; I₅₀ 2.3 (0.3) mg·l^–1.There were no clinical or biological adverse reactions to RP 48740 during the study.     

Treatment with the TLR7 agonist R848 induces regulatory T-cell-mediated suppression of established asthma symptoms

The evolution of allergic asthma is tightly controlled by effector and regulatory cells, as well as cytokines such as IL-10 and/or TGF-β, and it is widely acknowledged that environmental exposure to allergens and infectious agents can influence these processes. In this context, the recognition of pathogen-associated motifs, which trigger TLR activation pathways, plays a critical role with important consequences for disease progression and outcome. We addressed the question whether the TLR7 ligand resiquimod (R848), which has been shown to be protective in several experimental allergic asthma protocols, can also suppress typical asthma symptoms once the disease is established. To this end, we used an OVA-induced experimental model of murine allergic asthma in which R848 was injected after a series of challenges with aerosolized OVA. We found that the treatment attenuated allergic symptoms through a mechanism that required Tregs, as assessed by the expansion of this population in the lungs of mice having received R848, and the loss of R848-mediated suppression of allergic responses after in vivo Treg depletion. IL-10 provided only a minor contribution to this suppressive effect that was largely mediated through a TGF-β-dependent pathway, a finding that opens new therapeutic opportunities for the pharmacological targeting of Tregs.     

An investigation of inconsistent projections and artefacts in multi-pinhole SPECT with axially aligned pinholes

Multiple pinholes are advantageous for maximizing the use of the available field of view (FOV) of compact small animal single photon emission computed tomography (SPECT) detectors. However, when the pinholes are aligned axially to optimize imaging of extended objects, such as rodents, multiplexing of the pinhole projections can give rise to inconsistent data which leads to 'ghost point' artefacts in the reconstructed volume. A novel four pinhole collimator with a baffle was designed and implemented to eliminate these inconsistent projections. Simulation and physical phantom studies were performed to investigate artefacts from axially aligned pinholes and the efficacy of the baffle in removing inconsistent data and, thus, reducing reconstruction artefacts. SPECT was performed using a Defrise phantom to investigate the impact of collimator design on FOV utilization and axial blurring effects. Multiple pinhole SPECT acquired with a baffle had fewer artefacts and improved quantitative accuracy when compared to SPECT acquired without a baffle. The use of four pinholes positioned in a square maximized the available FOV, increased acquisition sensitivity and reduced axial blurring effects. These findings support the use of a baffle to eliminate inconsistent projection data arising from axially aligned pinholes and improve small animal SPECT reconstructions.     

Mid-term results of a new cementless hydroxyapatite coated anatomic unicompartmental knee arthroplasty

Introduction

We report the mid term results of a cement less HA coated unicompartmental knee prosthesis.

Material and methods

One hundred and fifty-nine Unicompartmental knee arthroplasties were done between 1995 and 2000 with ALPINA^® UNI, a cementless HA coated anatomic prosthesis. One hundred and twenty knees were available for the mid-term follow-up at a mean of 6.5 years.

Results

The mean IKS improved from 87.1 ± 22.1 points preoperatively to 168.2 ± 26.1 at the latest follow-up (P < 0.001). Ninety-four percent of the knees were rated good and excellent. The mean knee flexion has significantly improved from 120° preoperatively to 126° at the latest follow-up (P < 0.001). Ten knees were revised: three for degeneration of osteoarthritis in the opposite compartment of the knee, four for polyethylene insert fracture, one for severe polyethylene wear and two for tibial component loosening. When revision for any reason was defined as the end point, the 5-year Kaplan–Meier survival rate was 95.7% (95% confidence interval, 90.1–98.2%) and when revision due to implant mechanical failure (excluding degeneration of osteoarthritis in the opposite compartment of the knee) was defined as the end point, the 5-year survival rate was 96.6% (95% confidence interval, 91.2–98.7%).

Conclusion

This study confirms the reliability of HA coated unicompartimental knee replacement. With careful indications it seems to be a good alternative to osteotomy of total arthroplasty.     

Guide des pratiques pour le traitement de l'eau en unités d'autodialyse et à domicile

La dialyse doit être considérée comme une solution d'attente pour accéder a la transplantation. L'eau traitée in situ et utilisée de façon extemporanée pour la fabrication du dialysat, doit faire l'objet d'une vigilence de tous les instants. La grande difficule réside à mettre en place un contrôle identique en centre, en autodialyse et à domicile. La qualité physicochimique et bactériologique, la maintenance curative et préventive font l'objet d'une parfaite traçabilie. Toute la surveillance est documentée et regroupée dans le manuel assurance-qualité . Une unité de production d'eau pour hémodialyse est un dispositif médical ; elle est donc gérée par du personnel formé et compétent.