Neutrophil infiltration in co-housed littermates plays a key role in nasal transmission of Streptococcus pneumoniae in an infant mouse model.

Transmission plays an important role in establishing pneumococcal colonization. It comprises three key events: shedding to transmit, entering into a susceptible new host, and adhering to the mucosal surface. Shedding of pneumococci from the respiratory tract of a colonized host is a pivotal step in transmission. Using a co-housed littermate mouse model, we evaluated the importance of the susceptibility to colonization of Streptococcus pneumoniae TIGR4 strain shed from index pups to non-colonized naïve contact pups. Despite sufficient pneumococcal shedding from the colonized host, S. pneumoniae was not contagious between littermates. Neutrophils infiltrated the nasal mucosa of contact pups and contributed to susceptibility of pneumococcal colonization during the course of transmission. Rejection of pneumococcal colonization in the contact pups was associated with accumulation of neutrophils in the nasal mucosa. Inflammation, characterized by neutrophil infiltration, prevents newly entering pneumococci from adhering to the respiratory epithelium in contact mice, suggesting that it plays an important role in reducing the rate of transmission in the initial response of naïve susceptible hosts to pneumococcal acquisition. The initial response of contact mice may regulate neutrophil and/or macrophage infiltration and control the acquisition of existing pneumococci.

Detection of paranasal sinus opacification with digital tomosynthesis radiography: a clinical pilot study.

OBJECTIVE: We investigated the diagnostic accuracy of digital tomosynthesis (DT) radiography for detecting sinus opacification. METHODS: For 31 adult patients with signs suggestive of sinusitis who underwent both sinus multi-detector-row computed tomography and DT, 2 readers independently assessed opacification in the maxillary, ethmoid, frontal, and sphenoid sinuses by DT and in consensus determined the presence of opacification in each sinus by multi-detector-row computed tomography as a reference. We assessed the diagnostic accuracy of DT and interreader agreement with DT using Cohen κ statistics. RESULTS: For the maxillary, ethmoid, frontal, and sphenoid sinuses, opacification was identified in 81.7%, 75.9%, 59.3%, and 40.7%; the sensitivity/specificity for detecting opacification by DT were 93.9/72.7%, 79.5/71.4%, 93.8/72.7%, and 90.9/75.0% for reader 1 and 95.9/100.0%, 95.5/92.9%, 100.0/81.8%, and 81.8/75.0% for reader 2; the interreader agreement was 0.79, 0.42, 0.67, and 0.63, respectively. CONCLUSIONS: Digital tomosynthesis allows relatively accurate detection of sinus opacification with substantial interreader agreement for all the sinuses except the ethmoid sinuses.

Auditory evoked magnetic fields in children with functional hearing loss.

OBJECTIVES: Abnormal cortical responses in patients with functional hearing loss were evaluated by magnetoencephalography, which can better separate bihemispherical activity than electroencephalography. METHODS: Auditory evoked fields in response to 1 kHz or 2 kHz tone bursts at 80 dB sound pressure level were measured by a helmet-shaped magnetoencephalography system in 22 patients with functional hearing loss (18 females, mean age 13.2 years) as well as 5 control subjects under 10 years old. Waveform, latency, and equivalent current dipole of N100m responses were used to evaluate activity in the bilateral auditory cortices. RESULTS: Abnormal N100m of the contralateral response to the stimulated ear, either absence or delayed latency in comparison to normal adult subjects, was found in 6 of the 7 patients with functional hearing loss aged 9 years or younger, but in only 3 of the 15 patients aged 10 years or older. However, such abnormalities were also observed in younger control subjects. CONCLUSION: Auditory evoked field may be applied to objectively evaluate cortical auditory function in patients with functional hearing loss, but the normal findings for young children have not yet been established.

I(sK) Channel in Strial Marginal Cells. Voltage-Dependence, Ion-Selectivity, Inhibition by 293B and Sensitivity to Clofilium.

Strial marginal cells (SMC) and vestibular dark cells (VDC) are known to secrete K(+) into endolymph. Slowly-activating, voltage-dependent K(+) channels (KCNQ1/KCNE1; IsK; min K) have been identified in the apical membrane of these cells. Several experimental maneuvers known to increase or decrease transepithelial K(+) secretion have been found in VDC to change the current through these channels in the same ways. In both SMC and VDC the kinetics of activation and deactivation resemble those of the I(sK) channel exogenously expressed in Xenopus oocytes and endogenous to heart myocytes. The present study sought evidence that this current is indeed carried by I(sK) channels and that this current is the basis for transepithelial K(+) secretion. Both on-cell macro-patch recordings of the apical membrane and perforated-patch whole-cell recordings were made on SMC from gerbil in order to measure macroscopic cell currents. The on-cell current was found to 1) be K(+)-selective, 2) have a cation permeability sequence of K(+) ~ Rb(+) > Cs(+) >> Li(+) = Na(+), 3) be activated with a time constant of 1764 ± 413 ms by voltage steps from 0 to +40 mV, 4) be deactivated with a time constant of 324 ± 57 ms by voltage steps from 0 to -40 mV and 5) be reduced 84 ± 5% by bumetanide (10(-5) M), an inhibitor of K(+) secretion. The single-channel conductance of the apical currents in the homologous VDC was estimated by fluctuation analysis to be 1.6 pS. The potent inhibitor of I(sK) channels, chromanol 293B (10(-5) M), reduced the whole-cell current in SMC by 72 ± 10 %. Clofilium (10(-4) M), a putative I(sK) channel inhibitor known to have additional non-specific effects, led to a stimulation of both on-cell (by 598 ± 177%) and whole-cell (by 162 ± 18%) currents in gerbil SMC but to a decrease of whole-cell currents (by 39 ± 12%) in rat SMC. Taken together with other findings reviewed here, these results strongly argue that the slowly-activating, voltage-dependent conductance in the apical membrane of SMC is the I(sK) channel and provide additional evidence for the poor specificity of clofilium.