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1.
Childs Nerv Syst ; 29(7): 1207-10, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23503614

ABSTRACT

INTRODUCTION: With the increasing use of neuroimaging studies, the discovery of incidental neoplastic lesions is becoming more frequent. However, standard procedures are lacking, and little is known about their optimal management. CASE REPORT: We here present the case of a boy with a cerebellar mass incidentally discovered on a CT scan performed after head trauma. In another scan performed after another incident of head trauma 14 months earlier, the lesion could be seen after retrospective examination. In view of the asymptomatic clinical and stable radiological status and the presumed diagnosis of a low-grade glioma, a watch-and-wait strategy was elected. After clinical and radiological progression was observed, the tumour was resected, 2½ years after the initial imaging study. Histological evaluation revealed a WNT pathway-activated classical medulloblastoma. DISCUSSION: To our knowledge, this is the first description of such a long natural history and pre-symptomatic period of a medulloblastoma. The long period of stability followed by a period of accelerated tumour growth is compatible with increasing biological aggressiveness, possibly related to the stepwise accumulation of genetic changes.


Subject(s)
Cerebellar Neoplasms/diagnostic imaging , Incidental Findings , Medulloblastoma/diagnostic imaging , Watchful Waiting , Cerebellar Neoplasms/pathology , Cerebellar Neoplasms/surgery , Child , Disease Progression , Humans , Magnetic Resonance Imaging , Male , Medulloblastoma/pathology , Medulloblastoma/surgery , Tomography, X-Ray Computed
2.
Eur J Pediatr ; 168(10): 1277-9, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19148678

ABSTRACT

Feeding a mother's expressed breast milk to the wrong infant is a well-known misidentification error in neonatal intermediate care units (NICU) with potential harmful consequences for the neonate. In this study, we aimed to analyze the role of critical incident monitoring on detection and prevention of human breast milk confusions. The critical incident monitoring made us aware of this misidentification error on our NICU. Despite the implementation of system changes to make breast milk application clearer and safer, we failed to reduce the incidence of breast milk confusions.


Subject(s)
Medical Errors/prevention & control , Milk, Human , Quality Assurance, Health Care , Task Performance and Analysis , Chi-Square Distribution , Female , Humans , Infant, Newborn , Intensive Care Units, Neonatal
3.
Pain ; 141(3): 233-238, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19091469

ABSTRACT

Ionotropic gamma-aminobutyric acid (GABA(A)) receptors control the relay of nociceptive signals at several levels of the neuraxis. Experiments with systemically applied benzodiazepines, which enhance the action of GABA at these receptors, have suggested both anti- and pronociceptive effects. The interpretation of such experiments has been notoriously difficult because of confounding sedation. Here, we have used genetically engineered mice, which carry specific benzodiazepine-insensitive GABA(A) receptor subunits, to test whether diazepam, a frequently used classical benzodiazepine, exerts antihyperalgesia after systemic administration in the formalin test, a model of tonic nociception. In wild-type mice, systemic diazepam (3-30 mg/kg, p.o.) dose-dependently reduced the number of formalin-induced flinches during both phases of the test by about 40-70%. This antinociception was reversed by the benzodiazepine site antagonist flumazenil (10mg/kg, i.p.), but fully retained in GABA(A) receptor alpha1 point-mutated mice, which were resistant against the sedative action of diazepam. Experiments carried out in mice with two diazepam-insensitive subunits (alpha1/alpha2, alpha1/alpha3 and alpha1/alpha5 double point-mutated mice) allowed addressing the contribution of alpha2, alpha3 and alpha5 subunits to systemic diazepam-induced antihyperalgesia in the absence of sedation. The relative contributions of these subunits were alpha2 approximately alpha3>alpha5, and thus very similar to those found for intrathecal diazepam (0.09 mg/kg). Accordingly, SL-651498 (10mg/kg, p.o.), an "anxioselective" benzodiazepine site agonist with preferential activity at alpha2/alpha3 subunits, significantly reduced formalin-induced flinching in wild-type mice. We conclude that systemic diazepam exerts a genuine antihyperalgesic effect, which depends on spinal GABA(A) receptors containing alpha2 and/or alpha3 subunits.


Subject(s)
Anesthetics/therapeutic use , Diazepam/therapeutic use , Hyperalgesia/drug therapy , Point Mutation/genetics , Receptors, GABA-A/genetics , Analysis of Variance , Animals , Arginine/genetics , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Formaldehyde/adverse effects , Histidine/genetics , Hyperalgesia/chemically induced , Hyperalgesia/genetics , Indoles/therapeutic use , Male , Mice , Mice, Mutant Strains , Motor Activity/drug effects , Motor Activity/genetics , Physical Stimulation , Protein Subunits/genetics , Pyrroles/therapeutic use
4.
Neurosci Lett ; 437(3): 170-4, 2008 Jun 06.
Article in English | MEDLINE | ID: mdl-18406524

ABSTRACT

Inflammatory diseases and neuropathic insults trigger signaling cascades, which frequently lead to intense and long-lasting pain syndromes in affected patients. Such pain syndromes are characterized not only by an increased sensitivity to painful stimuli (hyperalgesia), but also by a qualitative change in the sensory perception of other, tactile stimuli (allodynia) and the occurrence of spontaneous pain in the absence of any sensory input. Long-term potentiation (LTP)-like changes in synaptic transmission between nociceptive C-fibers and spino-periaqueductal grey projection neurons as well as a loss of inhibitory control by GABAergic and glycinergic spinal dorsal horn neurons have repeatedly been proposed as underlying principles. While considerable evidence supports a significant contribution of C-fiber LTP to hyperalgesia, such monosynaptic plasticity cannot explain the occurrence of allodynia and spontaneous pain. In this review, we focus on mechanisms of synaptic dis-inhibition in inflammatory pain and propose that pathologically heightened pain sensitivity can be reversed by restoring synaptic inhibition with drugs that target specific spinal GABAA receptor subtypes.


Subject(s)
Neural Inhibition , Pain/pathology , Spinal Cord/physiopathology , Animals , Humans , Inflammation/complications , Models, Biological , Pain/etiology , Spinal Cord/pathology , Synapses/physiology
5.
Nature ; 451(7176): 330-4, 2008 Jan 17.
Article in English | MEDLINE | ID: mdl-18202657

ABSTRACT

Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobutyric acid (GABA)ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss. With the use of GABA(A)-receptor point-mutated knock-in mice in which specific GABA(A) receptor subtypes have been selectively rendered insensitive to benzodiazepine-site ligands, we show here that pronounced analgesia can be achieved by specifically targeting spinal GABA(A) receptors containing the alpha2 and/or alpha3 subunits. We show that their selective activation by the non-sedative ('alpha1-sparing') benzodiazepine-site ligand L-838,417 (ref. 13) is highly effective against inflammatory and neuropathic pain yet devoid of unwanted sedation, motor impairment and tolerance development. L-838,417 not only diminished the nociceptive input to the brain but also reduced the activity of brain areas related to the associative-emotional components of pain, as shown by functional magnetic resonance imaging in rats. These results provide a rational basis for the development of subtype-selective GABAergic drugs for the treatment of chronic pain, which is often refractory to classical analgesics.


Subject(s)
Pain/drug therapy , Pain/metabolism , Receptors, GABA-A/metabolism , Spinal Cord/metabolism , Analgesics/administration & dosage , Analgesics/metabolism , Analgesics/pharmacology , Analgesics/therapeutic use , Animals , Brain/drug effects , Brain/physiology , Capsaicin/pharmacology , Chronic Disease/drug therapy , Diazepam/administration & dosage , Diazepam/metabolism , Diazepam/pharmacology , Disease Models, Animal , Fluorobenzenes/metabolism , Fluorobenzenes/pharmacology , Formaldehyde , Ganglia, Spinal/cytology , Ganglia, Spinal/metabolism , Hot Temperature , Inflammation/chemically induced , Inflammation/drug therapy , Male , Mice , Neurons/drug effects , Neurons/metabolism , Organ Specificity , Pain/chemically induced , Pain/prevention & control , Protein Isoforms/chemistry , Protein Isoforms/metabolism , Protein Subunits/chemistry , Protein Subunits/metabolism , Rats , Rats, Wistar , Receptors, GABA-A/chemistry , Receptors, GABA-A/genetics , Spinal Cord/cytology , Spinal Cord/drug effects , Spinal Cord/physiopathology , Triazoles/metabolism , Triazoles/pharmacology
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