Differential vesicular distribution and trafficking of MMP‐2, MMP‐9, and their inhibitors in astrocytes

Astrocytes play an active role in the central nervous system and are critically involved in astrogliosis, a homotypic response of these cells to disease, injury, and associated neuroinflammation. Among the numerous molecules involved in these processes are the matrix metalloproteinases (MMPs), a family of zinc‐dependent endopeptidases, secreted or membrane‐bound, that regulate by proteolytic cleavage the extracellular matrix, cytokines, chemokines, cell adhesion molecules, and plasma membrane receptors. MMP activity is tightly regulated by the tissue inhibitors of MMPs (TIMPs), a family of secreted multifunctional proteins. Astrogliosis in vivo and astrocyte reactivity induced in vitro by proinflammatory cues are associated with modulation of expression and/or activity of members of the MMP/TIMP system. However, nothing is known concerning the intracellular distribution and secretory pathways of MMPs and TIMPs in astrocytes. Using a combination of cell biology, biochemistry, fluorescence and electron microscopy approaches, we investigated in cultured reactive astrocytes the intracellular distribution, transport, and secretion of MMP‐2, MMP‐9, TIMP‐1, and TIMP‐2. MMP‐2 and MMP‐9 demonstrate nuclear localization, differential intracellular vesicular distribution relative to the myosin V and kinesin molecular motors, and LAMP‐2‐labeled lysosomal compartment, and we show vesicular secretion for MMP‐2, MMP‐9, and their inhibitors. Our results suggest that these proteinases and their inhibitors use different pathways for trafficking and secretion for distinct astrocytic functions. © 2009 Wiley‐Liss, Inc.     

Long‐Term Mechanical Circulatory Support in Pediatric Patients

This retrospective study reviews our results regarding the long‐term support in pediatric patients using two ventricular assist systems between January 2008 and April 2014. We implanted the Berlin Heart EXCOR in 29 patients (median age 3.4 years [interquartile range (IQR) 0.2–16.5], median weight 13 kg [IQR 4.2–67.2]). Twenty‐two patients (75.8%) received a left ventricular assist device. Three patients (10.3%) had single‐ventricle physiology. One patient (3.4%) had mechanical mitral valve prosthesis. The HeartWare System was implanted in nine patients. The median age was 15.6 years (IQR 12.2–17.9), and the median weight was 54.9 kg (IQR 27.7–66). In the Berlin Heart group, the median support time was 65 days (IQR 4–619), with 3647 days of cardiac support. Nineteen patients (65.5%) were transplanted, six patients (20.7%) recovered, one patient (3.4%) is on support, and three patients (10.3%) died on support. Survival rate was 89.7%. Fourteen blood pumps had been exchanged. Four patients (13.8%) had local signs of infection, and three patients (10.3%) had neurological complications. In the HeartWare group, the median support time was 180 days (IQR 1–1124), with 2839 days of cardiac support. Four patients (44.4%) had local signs of infection, and three (33.3%) had neurological complications. Eight patients (88.9%) have been transplanted, and one patient (11.1%) died on support. Survival rate was 88.9%. Excellent survival is possible after long‐term mechanical circulatory support in patients with two‐ and single‐ventricle physiology with a low rate of adverse events.     

Late-onset spinal deformities in children treated by laminectomy and radiation therapy for malignant tumours

This is a retrospective study of 76 children who had had malignant tumours treated with laminectomy or laminoplasty and/or radiation therapy affecting the spine. Spinal tumours in children are extremely rare. However, their treatment can result in progressive spinal deformity. Radiation therapy affecting the growing spine can lead to asymmetric vertebral growth, causing kyphosis and/or scoliosis. These spinal deformities pose one of the most challenging problems for the spine surgeon. The aim of this article is to describe late-onset post-laminectomy/post-radiation spinal deformities and to evaluate the results of their treatment. Seventy-six children, with a mean age of 4 years and 7 months (range, 2 months to 16 years), underwent surgical removal of malignant tumours, between 1961 and 1995. Sixty-seven of them developed post-laminectomy/post-radiation spinal deformity. Conservative treatment consisted of bracing and corrective plaster casts. In 46 cases the deformity was treated surgically. A distraction plaster cast was used as preoperative preparation in the more severe and rigid curves, with or without neurological impairment. Surgery consisted of combined anterior and posterior fusion in 39 cases and posterior fusion in seven cases. Posterior instrumentation was used in 38 cases. The mean follow-up period was 6 years and 7 months (range, 9 months to 20 years and 2 months). Nine children did not develop deformity following the primary tumour treatment. One of them underwent laminectomy with posterolateral fusion and eight had laminoplasty combined with external immobilisation. Forty-six children developed iatrogenic kyphosis and underwent surgical correction from a mean of 75° pre-correction to a mean of 32°. The mean scoliotic angle correction was 66° preoperatively to 34° postoperatively. At follow-up, the mean correction loss was 7° in the sagittal plane and 5° in the coronal plane. Preoperative distraction plaster cast treatment resulted in a correction of 39% in kyphosis and of 58% in scoliosis, and in a partial or complete recovery of neurological deficits in all but one patient. In severe and rigid curves that develop following treatment of paediatric spinal tumours, preoperative application of a distraction plaster cast can reduce deformity and facilitate surgical correction. Furthermore, in the case of pure bony compression of the spinal cord due to the apical vertebra of the deformity, treatment with the distraction plaster can result in recovery from the neurological impairment. The prevention of post-laminectomy/post-radiation spine deformities is emphasised. Rigid external immobilisation for a period of 4 months in the cervical spine and of 6 months in the thoracic spine is recommended after both laminoplasty and laminectomy with posterolateral fusion.The research was carried out at Saint Vincent de Paul Hospital, Department of Pediatric Orthopaedic Surgery, Paris     

Chest re-exploration for complications after lung surgery.

BACKGROUND: Review of the most recent chest re-explorations for lung surgery complications may show methods by which risks can effectively be reduced. METHODS: The data on rethoracotomies following lung surgery over the past 14 years in our department were retrospectively reviewed. The indication, the type of operation, the outcome, and various factors influencing the postoperative mortality were analyzed. From 1983 to 1996, 1960 patients underwent primary thoracotomies for various lung diseases. Among these, 73 (3.7%) patients required re-exploration for various postoperative complications. RESULTS: Mean age was 56.8 years (15-80 years). There were 66 (90.4%) men and 7 (9.6%) women. The most common indication for rethoracotomy was hemorrhage in 38 (52%) patients. The source of bleeding was a mediastinal and/or bronchial blood vessel in 8 patients and an intercostal blood vessel in 6 patients. Six patients had to be reoperated because of hemorrhage from a major artery of the hilus. In 14 cases the postoperative hemothorax occurred without evident surgical origin. Further indications for rethoracotomy were bronchopleural fistula (BPF) in 13 (17.8%) patients, and persistent parenchymal leak in 8 (10.9%) patients. There were 8 additional causes distributed among the remaining 14 (19.3%) patients. The overall mortality rate was 17.8% (13/73), with the highest (38.4%) among BPF patients. CONCLUSIONS: Postoperative complications following lung surgery which require rethoracotomy are rare. The most common complication is postoperative bleeding. This is followed by bronchial stump insufficiency which is associated with the highest mortality and morbidity. Our experience shows that the need for re-exploration can hardly be reduced but the indication for re-exploration should be established as early as possible to avoid late complications.     

Methylene blue administration in severe systemic inflammatory response syndrome (SIRS) after thoracic surgery.

A 66-year-old male patient developed significant pleural effusion on the right side six years after coronary bypass grafting and mitral valve replacement. After pleurocentesis, hemo-pneumothorax developed and finally resulted in complete atelectasis of the right lung. Three weeks later, the patient was transferred to our department, and underwent a right lateral thoracotomy. The hematoma was removed and a complete decortication was performed. Four hours postoperatively the patient developed severe SIRS with beginning multiorgan failure. Even extremely high doses of norepinephrine could not raise the systemic vascular resistance. Single intravenous administration of methylene blue lead to significant and permanent improvement of the hemodynamic status.