Identification and evaluation of obstructive sleep apnea prior to adenotonsillectomy in children: a survey of practice patterns

OBJECTIVES: Some data suggest that the clinical diagnosis of obstructive sleep apnea (OSA) in a child should be confirmed by polysomnography before adenotonsillectomy (AT), but otolaryngology literature generally does not agree and few studies have examined surgical practice patterns. METHODS: We mailed, to 603 members of two North American otolaryngology societies, surveys about children aged 5.0-12.9 years upon whom they performed ATs in the previous year. RESULTS: A total of 183 otolaryngologists estimated that they had performed 24,000 ATs. Reported major surgical indications, not mutually exclusive, included recurrent throat infections (for 42% of procedures), obstructed breathing of any type (59%), OSA (39%), poor school performance (17%), and poor attention (11%). Pre-operative evaluations included an office-based, sleep-related history in 93% of children, any objective testing for OSA in <10%, and laboratory-based polysomnography in <5%. Surgeons with academic affiliations, higher volumes of ATs, and pediatric specialization reported lower percentages of ATs performed for recurrent tonsillitis as opposed to other indications. CONCLUSIONS: As a common indication for AT, OSA now rivals recurrent throat infection. No more than 12% of school-aged children who undergo AT for OSA have polysomnography prior to the procedure. Indications for AT may depend, in part, on practice settings and otolaryngologists' backgrounds.     

Cortical cyto- and chemoarchitecture in three small Australian marsupial carnivores: Sminthopsis macroura, Antechinus stuartii and Phascogale calura

The cyto- and chemoarchitecture of the cerebral cortex has been examined in three small (mouse-sized) polyprotodont marsupial carnivores from Australia (the stripe-faced dunnart, Sminthopsis macroura; the brown antechinus, Antechinus stuartii; and the red-tailed phascogale, Phascogale calura) in order to compare the cortical topography of these marsupials with that of diprotodontids, didelphids and eutherians. All three species studied had similar cortical cytoarchitecture. The isocortical surface was dominated by primary somatosensory (S1) and visual (V1) areas. Putative secondary sensory areas (S2, V2M, V2L) were also identified. The primary somatosensory cortex demonstrated clumps of granule cells in the presumptive mystacial field, whereas the primary visual area showed a distinctive chemical signature of intense calbindin immunoreactivity in layer IV. On the other hand, the primary auditory area was small and indistinct, but flanked by a temporal association area (TeA). A cytoarchitecturally distinct primary motor cortex (M1) with prominent pyramidal neurons in layer V and poor layer IV was identified medially to S1, and at rostral levels a putative secondary motor area was identified medial to M1. Transitional areas between isocortex and allocortical regions showed many cyto- and chemoarchitectural similarities to those reported for eutherian (and in particular rodent) cortex. Medially, two cingulate regions were found at rostral levels, with dysgranular and granular 'retrosplenial' areas identified caudally. Laterally, granular and agranular areas surrounded the rostral rhinal fissure, to be replaced by ectorhinal and perirhinal areas caudally. The findings indicate that the cyto- and chemoarchitectural features which characterize the iso- and allocortex in these small marsupial carnivores are similar to those reported in didelphids and eutherians and our findings suggest the existence of putative dedicated motor areas medial to the S1 field.     

Epilepsy surgery in children: results and predictors of outcome on seizures

PURPOSE: To retrospectively analyze the results on seizures of surgery in children with drug-resistant focal epilepsy. To identify the factors predicting seizure control among several presurgical, surgical, and postsurgical variables. METHODS: One hundred thirteen patients (67 male, 46 female), younger than 16 years, operated on from 1996 to 2004 and followed-up for at least 2 years were identified. Individualized microsurgical resections, aimed at removal of the epileptogenic zone, were performed according to the results of tailored presurgical evaluations, which included stereo-electroencephalographic recording with intracerebral electrodes when needed. Risk of seizure recurrence was assessed for the considered variables by bivariate and multivariate analysis. RESULTS: Mean age at surgery was 8.8 years, mean duration of epilepsy was 5.7 years, and mean age at seizure onset was 3.1 years. One hundred eight patients (96%) had an abnormal magnetic resonance imaging. At postoperative follow-up (mean duration 55.1 month), 77 patients (68%) were in Engel's class I, with 68 patients (60%) being seizure free (Engel's classes Ia and Ic). At multivariate analysis, variables associated with a significantly lower risk of seizure recurrence were unifocal lesion at MRI and older age at seizure onset (presurgical variables), temporal unilobar resection and complete lesionectomy (surgical variables), diagnosis of glial-neuronal tumors (postsurgical variables). CONCLUSIONS: Surgery is a valuable option for children with drug-resistant focal epilepsies which may provide excellent results in a considerable amount of cases. Since results of surgery for epilepsy strongly depend on the presurgical identification of the Epileptogenic Zone, future work should be focused on refinement and implementation of diagnostic strategies.     

Coupling of minor motor events and epileptiform discharges with arousal fluctuations in NFLE

Purpose: We recently demonstrated that in nocturnal frontal lobe epilepsy (NFLE) highly stereotyped minor motor events (MMEs, in the form of short‐lasting stereotyped movements involving the limbs, the axial musculature, and/or the head), could occur in either the presence or absence of an epileptiform discharge (ED). In lack of a systematic analysis, both MMEs and EDs were frequently observed to occur in association with arousal fluctuations. Hereby, in the same group of refractory NFLE subjects, we report a methodical neurophysiolgical investigation set out to investigate whether, and how, the arousal mechanism, monitored through visual scoring of the cyclic alternating pattern, modulates the expression of MMEs and EDs. Methods: The relationship of MMEs, EDs and arousal fluctuation was assessed in subjects explored using implanted electrodes. Results: The occurrence of both EDs and MMEs was associated with higher level of arousal (p < 0.0001). Multivariate logistic regression analysis shows a significant effect of interaction of EDs and MMEs during CAP sleep (p < 0.001). Conclusions: Both MMEs and EDs are associated with arousal. We suggest that recurrence of EDs in itself can induce an increase in arousal level, which in turn, through a gate effect, facilitate the occurrence of MMEs. Thus, MMEs wouldn't be a direct effect of EDs, but rather originate from an indirect effect related to loss of cortical inhibition, which is secondary to arousal. In this perspective MMEs may be regarded as the result of aspecific dishinibition, triggered by internal epileptiform stimuli, of innate motor patterns generated by central pattern generators (CPGs). The CPG system might represent, through arousal facilitation, the substrate of the heterogeneous expression of MMEs in NFLE.     

From bacterial genomes to novel antibacterial agents: discovery, characterization, and antibacterial activity of compounds that bind to HI0065 (YjeE) from Haemophilus influenzae

As part of a fully integrated and comprehensive strategy to discover novel antibacterial agents, NMR- and mass spectrometry-based affinity selection screens were performed to identify compounds that bind to protein targets uniquely found in bacteria and encoded by genes essential for microbial viability. A biphenyl acid lead series emerged from an NMR-based screen with the Haemophilus influenzae protein HI0065, a member of a family of probable ATP-binding proteins found exclusively in eubacteria. The structure-activity relationships developed around the NMR-derived biphenyl acid lead were consistent with on-target antibacterial activity as the Staphylococcus aureus antibacterial activity of the series correlated extremely well with binding affinity to HI0065, while the correlation of binding affinity with B-cell cytotoxicity was relatively poor. Although further studies are needed to conclusively establish the mode of action of the biphenyl series, these compounds represent novel leads that can serve as the basis for the development of novel antibacterial agents that appear to work via an unprecedented mechanism of action. Overall, these results support the genomics-driven hypothesis that targeting bacterial essential gene products that are not present in eukaryotic cells can identify novel antibacterial agents.     

Novel propeptin analog, propeptin-2, missing two amino acid residues from the propeptin C-terminus loses antibiotic potency

A novel inhibitor of prolyl endopeptidase, the propeptin analog propeptin-2 (C105H130N24O(24)), missing two amino acid residues from the propeptin C-terminus was isolated from the fermentation broth of propeptin-producing Microbispora sp. SNA-115 grown using a large inoculum. It shows the same enzyme inhibition activity as propeptin against prolyl endopeptidase (Ki=1.5 microM), but its antimicrobial activity against Mycobacterium phlei is more than 100-fold lower.     

Sequence and expression of NAPlr is conserved among group A streptococci isolated from patients with acute poststreptococcal glomerulonephritis (APSGN) and non-APSGN

BACKGROUND: The relation of nephritis-associated plasmin receptor (NAPlr) as a nephritogenic antigen in group A streptococci (GAS), to acute poststreptococcal glomerulonephritis (APSGN) and the potential of specific strains to cause APSGN are not fully understood. It would be helpful to determine whether certain GAS strains from APSGN patients specifically express NAPlr and whether strains from non-APSGN patients express lower levels or an altered form of NAPlr. METHODS: The sequence and levels of expression of NAPlr were assayed for strains of GAS isolated from patients with APSGN, pharyngitis, scarlet fever or toxic shock-like syndrome. Findings were evaluated with respect to naplr gene sequence, expression level of NAPlr, serotype and disease type. RESULTS: In GAS strains from both APSGN and non-APSGN patients, the naplr gene showed few or no nucleotide alterations, and both types of GAS strains expressed NAPlr in vitro. There were no obvious differences in naplr gene sequence, expression of NAPlr, serotype or disease type between the GAS strains. In addition, groups C and G streptococci also carried a conserved naplr gene and expressed NAPlr in vitro. CONCLUSIONS: These groups of streptococci that express NAPlr should be associated with APSGN, and this association may be independent of serotype or disease type.