Airway hyper-reactivity mediated by B-1 cell immunoglobulin M antibody generating complement C5a at 1 day post-immunization in a murine hapten model of non-atopic asthma

Contact skin immunization of mice with reactive hapten antigen and subsequent airway challenge with the same hapten induces immediate airflow obstruction and subsequent airway hyper‐reactivity (AHR) to methacholine challenge, which is dependent on B cells but not on T cells. This responsiveness to airway challenge with antigen is elicited as early as 1 day postimmunization and can be adoptively transferred to naïve recipients via 1‐day immune cells. Responses are absent in 1‐day immune B‐cell‐deficient JH^?/? mice and B‐1 B‐cell‐deficient xid male mice, as well as in recipients of 1‐day immune cells depleted of cells with the B‐1 cell phenotype (CD19⁺ B220⁺ CD5⁺). As B‐1 cells produce immunoglobulin M (IgM), we sought and found significantly increased numbers of anti‐hapten IgM‐producing cells in the spleen and lymph nodes of 1‐day immune wild‐type mice, but not in xid mice. Then, we passively immunized naive mice with anti‐hapten IgM monoclonal antibody and, following airway hapten challenge of the recipients, we showed both immediate airflow obstruction and AHR. In addition, AHR was absent in complement C5 and C5a receptor‐deficient mice. In summary, this study of the very early elicited phase of a hapten asthma model suggests, for the first time, a role of B‐1 cells in producing IgM to activate complement to rapidly mediate asthma airway reactivity only 1 day after immunization.     

Consumption of solutions containing sodium chloride is enhanced in female oxytocin-deficient mice

Intact and ovariectomized oxytocin (OT)-deficient (OT-/-) and wild-type (OT+/+) mice were tested for consumption of 0.5 M NaCl solution or tap water in a 2-bottle choice test. During 3 days of acclimation, voluntary ingestion of NaCl was equal between genotypes. After overnight fluid deprivation, intact OT-/- mice ingested 2 times more NaCl solution than OT+/+ mice in the 6th hr, but not the 1st hr, after reintroduction of fluid. Ovariectomized mice consumed less than intact mice after overnight fluid deprivation. When a 0.2 M NaCl solution was administered for 6 days in ovariectomized mice, OT-/- mice voluntarily consumed greater amounts than OT+/+ mice. After overnight fluid deprivation, consumption by OT-/- mice was 3 times that of OT+/+ mice at 1 hr and 2-fold greater after 6 hr. Enhanced intake of NaCl-containing solutions in female OT-/- mice suggests that central OT may be an important inhibitor of sodium consumption.     

Gamma Knife Radiosurgery of the Glomus Jugulare Tumour – Early Multicentre Experience

Leksell Gamma Knife was used to treat 66 patients with glomus jugulare tumour at 6 European sites between 1992-1998. The age of the patients ranged between 18-80 years (median 54 years). Gamma Knife radiosurgery was a primary treatment in 30 patients (45. 5%). Open surgery preceded radiosurgery in 24 patients (36.4%), embolisation in 14 patients (21.2%) and fractionated radiotherapy in 5 patients (7.6%). The volume of the tumour ranged 0.5-27 cm(3) (median 5,7 cm(3)). The minimal dose to the tumour margin ranged between 10-30 Gy (median 16.5 Gy). After radiosurgery 52 patients were followed, the follow up period was 3-70 months (median 24 months). Neurological deficit improved in 15 patients (29%) and deteriorated in 3 patients (5,8%), one transient and two persistant. Neuroradiological follow up using MRI or CT was performed in 47 patients 4-70 months (median 24 months) after radiosurgery. Tumour size decreased in 19 patients (40%) while in the remaining 28 patients (60%) no change in the tumour volume was observed. None of the tumours increased in volume during the observation period. Control angiography was performed in 6 patients. Pathological vascularisation completely disappeared in one patient, reduced in two and there was no change in the remaining three. Radiosurgery proves to be a safe treatment for glomus jugulare tumour with no mortality and no acute morbidity. Because of its naturally slow growth rate, up to 10 years of follow up will be necessary to establish a cure rate after radiosurgery for these lesions.     

Even a “pigtail” distal end catheter can enter the epidural space after continuous paravertebral block

A woman with a medical history of breast cancer presented with chronic pain of the right hemithorax. To alleviate pain, a continuous paravertebral block was performed using a pigtail end catheter, introduced using ultrasound visualization (transversal technique at the inferior articular process of T6). Complete pain relief was observed. A few hours later, urinary retention was diagnosed and discharge from the ambulatory setting was canceled. On the following day, a new injection of local anesthetics through the catheter triggered paresthesia in the contralateral leg and a new urinary retention was diagnosed. A CT scan confirmed the epidural misplacement of the catheter. The latter was withdrawn, and the patient was released to home after the complete disappearance of her neurological symptoms. This case report highlights the risk of inadvertently misplacing the catheter into the epidural space during thoracic paravertebral block, even with a “pigtail” distal end type of catheter.     

Chronic Cancer-Related Pain: Continuous Perineural Infusion of Local Anesthetics as Alternative to Systemic Analgesic Drugs

Pain is a major concern for patients suffering from cancer. Although opioid drugs remain the gold standard for treatment of pain, little is known about the interest of continuous analgesia techniques as alternative. The aim of the present article is to detail the feasibility and to present the diversity of continuous perineural infusion of local anesthetic. A series of five patients suffering from different cancer-related pain is presented. A continuous perineural block was proposed to patients presenting with unbearable pain in an area innervated by a plexus or a nerve despite parenteral analgesic pharmacotherapy. All blocks were performed in a surgical theatre under sterile conditions. An initial bolus dose with 3.75 mg/mL ropivacaine was injected followed by a continuous infusion of 2 mg/mL of ropivacaine. Patient-controlled perineural analgesia was started at home by a nursing network. The technique, the efficacy, and the side effects were reported. Complete pain relief was noted 15 minutes after local anesthetic injection in the five cases, and efficacy was maintained during the following days at home, with no other analgesic treatment required. One patient restarted working a few weeks after catheter insertion. The catheter duration lasted for 12 to 110 days. One catheter was removed because of local anesthetic leak at the puncture point. Some paresthesia was noted in one patient. No other side effect was noted. No infection was reported. In selected patients, continuous perineural infusion of local anesthetics appears to be an attractive alternative to parenteral opioids for cancer-related pain. Further investigation is warranted to better define the place of these techniques in the armamentarium of cancer-related pain treatment.     

Prognostic value of aerobic capacity and exercise oxygen pulse in postaortic dissection patients

BackgroundAlthough recommendations encourage daily moderate activities in post aortic dissection, very little data exists regarding cardiopulmonary exercise testing (CPET) to personalize those patient''s physical rehabilitation and assess their cardiovascular prognosis.DesignWe aimed at testing the prognostic insight of CPET regarding aortic and cardiovascular events by exploring a prospective cohort of patients followed‐up after acute aortic dissection.MethodsPatients referred to our department after an acute (type A or B) aortic dissection were prospectively included in a cohort between September 2012 and October 2017. CPET was performed once optimal blood pressure control was obtained. Clinical follow‐up was done after CPET for new aortic event and major cardio‐vascular events (MCE) not directly related to the aorta.ResultsAmong the 165 patients who underwent CPET, no adverse event was observed during exercise testing. Peak oxygen pulse was 1.46(1.22‐1.84) mlO2/beat, that is, 97 (83–113) % of its predicted value, suggesting cardiac exercise limitation in a population under beta blockers (92% of the population). During a follow‐up of 39(20‐51) months from CPET, 42 aortic event recurrences and 22 MCE not related to aorta occurred. Low peak oxygen pulse (<85% of predicted value) was independently predictive of aortic event recurrence, while low peak oxygen uptake (<70% of predicted value) was an independent predictor of MCE occurrence.ConclusionCPET is safe in postaortic dissection patients should be used to not only to personalize exercise rehabilitation, but also to identify those patients with the highest risk for new aortic events and MCE not directly related to aorta.