Pediatric intracranial pressure monitoring in hypoxic and nonhypoxic brain injury

We reviewed the results of all pediatric patients undergoing intracranial pressure (ICP) monitoring in a 2-year period at our institution. The outcome of patients suffering hypoxia or ischemic injuries (HII) is compared to those suffering non-hypoxic or non-ischemic injuries (NHII). Thirty-four patients had ICP monitors placed during the study period. Inconplete patient information led to the exclusion of 5 patients. An additional 5 patients were excluded because no measures to control ICP were taken after the monitor was placed. Twenty-four patients required treatment for raised ICP (hyperventilation, 24; mannitol, 19; barbiturate coma, 6). Admission Glasgow Coma Score in patients suffering HII (median score 5) and NHII (median score 6) were not significantly different (Mann-Whitney U Test). Only 2 of 8 patients with HII were near-drowning vietims. The remaining 6 had HII from other causes (5 survivors of various forms of asphyxia and 1 of cardiac arrest). All 8 patients had poor outcomes (1 severely disabled; 7 died). The 16 patients with NHII had a variety of diagnoses (6 trauma, 5 encephalitis, 4 bacterial meningitis, 1 diabetic ketoacidosis). Among these, 6 had good outcomes and 10 poor outcomes (2 severely disabled, 2 vegetative, and 6 died). The difference in outcome between patients with NHII and HII is significant at P=0.059 (Fischer Exact test). Patients with NHII may benefit from ICP monitoring. Patients with HII from near-drowning and other causes did not appear to benefit from ICP monitoring and interventions directed at controlling ICP.     

P2X(7) receptors are expressed during mouse nephrogenesis and in collecting duct cysts of the cpk/cpk mouse.

BACKGROUND: Purinergic receptors are cell-surface molecules that bind extracellular nucleotides, notably ATP. The P2X family includes seven nonselective ion channels with one member, P2X(7), implicated in cytolytic pore formation and cell death. MATERIALS AND METHODS: We sought P2X(7) expression in mouse nephrogenesis and cpk/cpk renal cyst growth, conditions in which both proliferation and apoptosis are prominent. RESULTS: P2X(7) immunolocalized to condensed metanephric mesenchyme: both proliferation and apoptosis were detected in this compartment, assessed by proliferating cell nuclear antigen expression and propidium iodide-stained pyknotic nuclei respectively. Later in nephrogenesis, P2X(7) was detected in collecting ducts, a pattern persisting to maturity. A mesenchymal to epithelial shift of P2X(7) expression was also documented in ureter development. In cpk/cpk kidneys, P2X(7)-expressing collecting duct cysts dominated histology from two weeks until four weeks after birth, when animals die from uremia. In polycystic kidneys pyknotic nuclei were rarely identified in P2X(7)-expressing epithelia, but were detected between cysts, consistent with a non-apoptotic role for P2X(7) in cyst enlargement. CONCLUSION: P2X(7) is expressed during normal nephrogenesis and in a model of congenital polycystic kidney disease. Further experiments are necessary to define possible functions of P2X(7) in these settings.     

Klinische Erfahrungen mit der Knorpel-Knochen-Transplantation

The treatment of deep cartilage defects in load-bearing joints is a problem that still has no satisfactory solution. Full-thickness defects of the articular cartilage rarely heal spontaneously, usually leaving damage that can lead to early arthrosis. Techniques currently available for the treatment of chondral defects include abrasion, drilling, micro-fracturing, transplantation of tissue autografts and allografts, and cell transplantation. Osteochondral autograft transplantation is currently the only surgical cartilage repair technique known to lead to the formation of genuine hyaline articular cartilage and its retention at least in the medium term. The Draenert method, in which a water-cooled diamond bone-cutting system is used, is an effective procedure for resurfacing the joints affected by localised cartilaginous defects, even when there is also severe bone loss. Donor-side morbidity can be kept to a minimum by filling the defect caused by harvesting with a press-fit cylinder of cancellous bone covered with periosteum for protection.     

Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

Correction of head movement on PET studies: comparison of methods.

Head movement presents a continuing problem in PET studies. Head restraint minimizes movement but is unreliable, resulting in the need to develop alternative strategies. These include frame-by-frame (FBF) realignment or use of motion tracking (MT) during the scan to realign PET acquisition data. Here we present a comparative analysis of these 2 methods of motion correction. METHODS: Eight volunteers were examined at rest using (11)C-raclopride PET with the radioligand administered as a bolus followed by constant infusion to achieve steady state. Binding potential (BP) was estimated using the ratio method during 2 periods of the scan at steady state. Head movement was compensated by using coregistration between frames (FBF) and 3 methods using MT measurements of head position acquired with a commercially available optical tracking system. RESULTS: All methods of realignment improved test-retest reliability and noise characteristics of the raw data, with important consequences for the power to detect small changes in radiotracer binding, and the potential to reduce false-positive and false-negative results. MT methods were superior to FBF realignment using coregistration on some indices. CONCLUSION: Such methods have considerable potential to improve the reliability of PET data with important implications for the numbers of volunteers required to test hypotheses.