Phrenic Nerve Stimulation for Central Ventilatory Failure with Bipolar and Four-Pole Electrode Systems

A multi-channel phrenic nerve stimulator developed in Tampere has been implanted into seven patients with C2-tetraplegia and into three patients with central sleep apneas. Six bipolar cuff electrodes were implanted bilaterally into the neck. Two four-pole cuff and 14 four-pole noncuff electrodes were used in seven patients and to replace one bipolar electrode. Four-pole electrodes were implanted within the thorax. Seven patients achieved total independence from conventional ventilators within 4 months of implantation, and one for 18 hours each day. Two patients died 12 days and 3 months after implantation and two patients after having achieved independence from mechanical ventilators from causes unrelated to the stimulators. Reoperations were necessary because of dislocation of receivers, electrodes, electrode lesions, nerve injuries, and technical failures in seven patients. Most of the problems appeared in two patients with obesity and in three patients with very thin phrenic nerves. Single unit prototypes failed technically more frequently than units of prototype serial fabrication. New electrode design, progress in the manufacture of receivers, and improved implantation technique should help to diminish failures in future.     

体外膈肌起搏在肺心病呼吸衰竭治疗中的应用

本文报告30例肺心病所致呼吸衰竭患者,经体外膈肌起博治疗后,呼吸衰竭症状改善,PaCO_2明显下降,PaO_2上升,提示体外膈肌起博在急慢性呼衰治疗中,具有降低高碳酸血症和提高氧分压疗效。并具有无创性,操作简易等优点,为呼吸乐统疾病提供一个新的治疗手段。     

Predictors of outcome for children requiring respiratory extra-corporeal life support: implications for inclusion and exclusion criteria

Objectives  A range of children receive extra-corporeal life support (ECLS) for respiratory failure, but there is little published data on this group. Our aims were: (1) to analyse predictors of outcome and (2) comment on inclusion and exclusion criteria. Design  Retrospective review. Setting  Tertiary ECLS centre. Patients  A total of 124 children categorised as ‘paediatric respiratory ECLS’ from July 1992 to December 2005. Results  Fifty-three percent of children had one or more co-morbid conditions; the median age was 10.1 (IQR 3–34) months; the median ECLS duration was 9 (IQR 5–17) days; survival to discharge was 62% and at 1 year was 59%. Although survival varied according to primary reason for ECLS (range 36–100%), after adjustment for this, the presence of a co-morbid condition was unrelated to mortality (OR = 1.49, 95% CI 0.65, 3.42, P = 0.34) Predictors of mortality were increased pre-ECLS oxygenation index (OR = 1.09, 95% CI 1.00, 1.18, P = 0.05) and shock (OR 2.53, 95% CI 1.21, 5.28, P = 0.01). The relationship between mortality and end organ dysfunction (OR 2.12, 95% CI 0.89, 5.02, P = 0.09) and greater number of pre-ECLS ventilator days (OR 1.10, 95% CI 0.99, 1.22, P = 0.08) was less conclusive. Conclusions  Pre-existing co-morbid conditions may predispose children to develop severe respiratory failure but with careful case selection, do not appear to reduce the chance of survival. Severity of pulmonary dysfunction determined by OI and shock were key predictors of outcome and should remain important determinants of referral for ECLS.     

Blood Kidney Injury Molecule-1 Is a Biomarker of Acute and Chronic Kidney Injury and Predicts Progression to ESRD in Type I Diabetes

Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5–15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.     

Shiga Toxin Promotes Podocyte Injury in Experimental Hemolytic Uremic Syndrome via Activation of the Alternative Pathway of Complement

Shiga toxin (Stx)–producing Escherichia coli is the offending agent of postdiarrhea-associated hemolytic uremic syndrome (HUS), a disorder of glomerular ischemic damage and widespread microvascular thrombosis. We previously documented that Stx induces glomerular complement activation, generating C3a responsible for microvascular thrombosis in experimental HUS. Here, we show that the presence of C3 deposits on podocytes is associated with podocyte damage and loss in HUS mice generated by the coinjection of Stx2 and LPS. Because podocyte adhesion to the glomerular basement membrane is mediated by integrins, the relevance of integrin-linked kinase (ILK) signals in podocyte dysfunction was evaluated. Podocyte expression of ILK increased after the injection of Stx2/LPS and preceded the upregulation of Snail and downregulation of nephrin and α-actinin-4. Factor B deficiency or pretreatment with an inhibitory antibody to factor B protected mice against Stx2/LPS-induced podocyte dysregulation. Similarly, pretreatment with a C3a receptor antagonist limited podocyte loss and changes in ILK, Snail, and α-actinin-4 expression. In cultured podocytes, treatment with C3a reduced α-actinin-4 expression and promoted ILK-dependent nuclear expression of Snail and cell motility. These results suggest that Stx-induced activation of the alternative pathway of complement and generation of C3a promotes ILK signaling, leading to podocyte dysfunction and loss in Stx-HUS.