Increased Myeloid Cell Production and Lung Bacterial Clearance in Mice Exposed to Cigarette Smoke.

Pneumonia is a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD). Although most patients with COPD are smokers, the effects of cigarette smoke exposure on clearance of lung bacterial pathogens and on immune and inflammatory responses are incompletely defined. Here, clearance of Streptococcus pneumoniae and Pseudomonas aeruginosa and associated immune responses were examined in mice exposed to cigarette smoke or after smoking cessation. Mice exposed to cigarette smoke for 6 weeks or 4 months demonstrated decreased lung bacterial burden compared with air-exposed mice when infected 16 to 24 hours after exposure. When infection was performed after smoke cessation, bacterial clearance kinetics of mice previously exposed to smoke reversed to levels comparable to those of control mice, suggesting that the observed defects were not dependent on adaptive immunological memory to bacterial determinants found in smoke. Comparing cytokine levels and myeloid cell production before infection in mice exposed to cigarette smoke with mice never exposed or after smoke cessation revealed that reduced bacterial burden was most strongly associated with higher levels of IL-1ß and granulocyte-macrophage colony-stimulating factor in the lungs and with increased neutrophil reserve and monocyte turnover in the bone marrow. Using Serpinb1a-deficient mice with reduced neutrophil numbers and treatment with granulocyte colony-stimulating factor showed that increased neutrophil numbers contribute only in part to the effect of smoke on infection. Our findings indicate that cigarette smoke induces a temporary and reversible increase in clearance of lung pathogens, which correlates with local inflammation and increased myeloid cell output from the bone marrow.

Bilateral Granulomatous and Fibrinoheterophilic Otitis Interna due to Pseudomonas aeruginosa in a Captive Little Bustard ( Tetrax tetrax ).

A captive juvenile little bustard ( Tetrax tetrax ) was presented for acute onset of right head tilt and right circling. The bird failed to respond to supportive care and systemic antibiotic therapy. A bilateral granulomatous and fibrinoheterophilic otitis interna due to Pseudomonas aeruginosa was diagnosed postmortem by histopathologic examination and bacterial culture. In bustards, Pseudomonas species have been documented in the normal bacterial flora of the oropharynx and are frequently reported in upper respiratory tract infections. This is the first report of a peripheral vestibular syndrome due to P aeruginosa otitis interna in a bustard species. Pseudomonas aeruginosa should be included as a possible cause of otitis and peripheral vestibular syndrome in bustards.

Otitis interna induced by Cryptococcus neoformans var. grubii in a cat.

Cryptococcus neoformans var. grubii was identified at necropsy in a case of bilateral otitis interna in a 7-year-old, female, domestic shorthair cat with a 9-day history of acute onset of vestibular disease. Gross examination, including that of the middle and inner ears, was unremarkable. Histologically, the auricular vestibuli, cochleae, and semicircular canals were bilaterally affected by granulomatous inflammation with extracellular and intrahistiocytic yeasts. The yeasts and associated inflammation obstructed and disrupted perilymphatic and endolymphatic spaces of the inner ears. Disruption of the saccular and utricular maculae, cristae ampularis, and organ of Corti, as well as changes in the endolymphatic and perilymphatic fluids, probably impaired the vestibular and auditory functions of this cat. The route of infection was most likely hematogenous.

Severe cochlear inflammation and vestibular syndrome in an experimental model of Streptococcus suis infection in mice.

Hearing impairment is a common and frequently permanent sequel of Streptococcus suis meningitis in humans. Nevertheless, mechanisms underlying the development of cochlear damage have not been addressed so far. In the present work, we characterized a mouse model of suppurative labyrinthitis and meningitis induced by a systemic infection with S. suis and studied the impact of the injected bacterial dosage on the progression of such inflammatory events. We observed that high infection doses of bacteria lead to sustained bacteremia, with an increase in the permeability of the blood-labyrinth and blood-brain barriers, causing suppurative labyrinthitis and meningitis, respectively. However, in mice infected with a low dose of S. suis, bacteria disappeared quickly from blood, hence, cochlear inflammation and meningitis were not consistent features. This model of S. suis infection seems ideal to evaluate novel drugs that may help alleviate the negative consequences of such important sequelae of S. suis-induced meningitis and labyrinthitis.

Otopathologic Analysis of Patterns of Postmeningitis Labyrinthitis Ossificans.

OBJECTIVE: Labyrinthitis ossificans (LO) may occur following meningitis and, in cases where cochlear implantation is indicated, complicate electrode insertion. LO is critical to identify for successful cochlear implantation, and histopathology is more sensitive than imaging for identification of LO. Herein we utilize otopathologic techniques to study the timing and location of intracochlear tissue formation following meningitic labyrinthitis (ML). STUDY DESIGN: Retrospective review. SETTING: Academic institution. METHODS: Temporal bone specimens with a history of bacterial ML were histologically evaluated. The location and extent of intracochlear tissue formation within the scala tympani (ST) and scala vestibuli (SV) were graded, and spiral ganglion neurons were counted. RESULTS: Fifty-one temporal bones were identified: 32 with no intracochlear tissue formation, 9 with fibrosis alone, and 10 with LO. Fibrosis was identified as early as 1.5 weeks after ML, while ossification was found only in specimens that survived multiple years after ML. All LO cases showed ossification of the ST at the round window membrane (RWM) with continuous extension throughout the basal turn. Extent of SV ossification correlated with that in the ST but showed frequent isolated distal involvement of the cochlea. Spiral ganglion neuron counts were lower than those in age-matched controls. CONCLUSION: In this human temporal bone study, we found that postmeningitic LO results in ossification at the RWM with continuous extension into the ST of the basal turn and variable involvement of the SV. Identification of a patent basal turn beyond RWM ossification of the ST should permit full electrode insertion. LEVEL OF EVIDENCE: Retrospective review.

Spiral ligament fibrocyte-derived MCP-1/CCL2 contributes to inner ear inflammation secondary to nontypeable H. influenzae-induced otitis media.

BACKGROUND: Otitis media (OM), one of the most common pediatric infectious diseases, causes inner ear inflammation resulting in vertigo and sensorineural hearing loss. Previously, we showed that spiral ligament fibrocytes (SLFs) recognize OM pathogens and up-regulate chemokines. Here, we aim to determine a key molecule derived from SLFs, contributing to OM-induced inner ear inflammation. METHODS: Live NTHI was injected into the murine middle ear through the tympanic membrane, and histological analysis was performed after harvesting the temporal bones. Migration assays were conducted using the conditioned medium of NTHI-exposed SLFs with and without inhibition of MCP-1/CCL2 and CCR2. qRT-PCR analysis was performed to demonstrate a compensatory up-regulation of alternative genes induced by the targeting of MCP-1/CCL2 or CCR2. RESULTS: Transtympanic inoculation of live NTHI developed serous and purulent labyrinthitis after clearance of OM. THP-1 cells actively migrated and invaded the extracellular matrix in response to the conditioned medium of NTHI-exposed SLFs. This migratory activity was markedly inhibited by the viral CC chemokine inhibitor and the deficiency of MCP-1/CCL2, indicating that MCP-1/CCL2 is a main attractant of THP-1 cells among the SLF-derived molecules. We further demonstrated that CCR2 deficiency inhibits migration of monocyte-like cells in response to NTHI-induced SLF-derived molecules. Immunolabeling showed an increase in MCP-1/CCL2 expression in the cochlear lateral wall of the NTHI-inoculated group. Contrary to the in vitro data, deficiency of MCP-1/CCL2 or CCR2 did not inhibit OM-induced inner ear inflammation in vivo. We demonstrated that targeting MCP-1/CCL2 enhances NTHI-induced up-regulation of MCP-2/CCL8 in SLFs and up-regulates the basal expression of CCR2 in the splenocytes. We also found that targeting CCR2 enhances NTHI-induced up-regulation of MCP-1/CCL2 in SLFs. CONCLUSIONS: Taken together, we suggest that NTHI-induced SLF-derived MCP-1/CCL2 is a key molecule contributing to inner ear inflammation through CCR2-mediated recruitment of monocytes. However, deficiency of MCP-1/CCL2 or CCR2 alone was limited to inhibit OM-induced inner ear inflammation due to compensation of alternative genes.

Not 'just' a foreign body in the ear canal.

Foreign bodies are commonly seen by the Ear, Nose and Throat emergency team with cotton wool being the most common aural foreign body seen in the adult population. Most complications secondary to aural foreign bodies described in the literature are minor and rarely require any surgical intervention. Here, we present two cases with impacted cotton wool as aural foreign bodies which resulted in suppurative labyrinthitis and osteomyelitis causing profound sensorineural hearing. These cases highlight the importance of considering aural foreign bodies in the differential diagnosis in those presenting with unilateral symptoms as significant complications, although rare, can occur, particularly in those with delayed diagnosis.

Meningitis resulting in hearing loss and labyrinthitis ossificans - does the causative organism matter?

Our aim was to demonstrate whether one causative agent of meningitis is more likely to cause profound hearing loss and labyrinthitis ossificans. We obtained data from the New South Wales health department for cases of meningitis between 1995 and 2005 (1568 cases) and the Sydney Cochlear Implant Centre for cochlear implant patients with hearing loss secondary to meningitis from 1984 to 2005 (70 ears in 59 patients). The aetiological agents were compared with regard to their ability to cause profound hearing loss and cochlear ossification. Neisseria meningitidis resulted in 56.9% of cases of meningitis and 11.4% of the cases of profound hearing loss resulting in cochlear implantation (incidence of profound hearing loss of 0.4%). Streptococcus pneumoniae, however, caused 41.1% of meningitis but 85.7% of cochlear implantation (incidence of 4.6%). Labyrinthitis ossificans was more common after infection with Streptococcus pneumoniae but there was no statistically significant difference between Streptococcus pneumoniae, Haemophilus influenzae or Neisseria meningitidis for labyrinthitis ossificans (p = 0.45, chi-squared test). In conclusion Neisseria meningitidis meningitis carries a very low risk of profound hearing loss but Streptococcus pneumoniae meningitis a significantly higher risk.

Otitis interna (labyrinthitis) associated with Salmonella enterica arizonae in turkey poults.

Otitis interna was diagnosed in five 9-to-21-day-old turkey poults with clinical signs of paralysis, opisthotonus, torticollis, blindness, and increased mortality. Gross and microscopic lesions in the poults included omphalitis, typhlitis, hepatitis, meningoencephalitis, ophthalmitis, neuritis and ganglionitis of the vestibulocochlear nerve, and otitis interna. Salmonella enterica arizonae was isolated from the brains, eyes, intestines, yolk sacs, and livers of poults. Birds with otitis interna also had meningoencephalitis. It is most likely that the S. enterica arizonae infection spread from the brain to the internal ears through the vestibulocochlear nerve. This is the first documentation of otitis interna caused by bacteria in an avian species.

Pseudomonas aeruginosa otitis media and interna in a chinchilla ranch.

Pseudomonas aeruginosa has been associated with conjunctivitis, enteritis, pneumonia, septicemia, sudden death, and abortion in chinchillas. This case report describes an unusual clinical presentation and diagnosis of P. aeruginosa otitis media and interna with neurologic manifestations. To our knowledge, this clinical presentation has not been reported previously in chinchillas.

Round window membrane and labyrinthine pathological changes: an overview.

The round window membrane is considered the most likely pathway from the middle to the inner ear. Various substances placed in the middle ear have been seen to pass through the round window membrane. Once toxic substances or inflammatory mediators such as cytokines and nitric oxide enter the inner ear, various inner ear sequelae such as labyrinthitis, endolymphatic hydrops, sensorineural hearing loss or more insidious diseases can occur.

The Impact of Postmeningitic Labyrinthitis Ossificans on Speech Performance After Pediatric Cochlear Implantation.

OBJECTIVE: 1) To characterize pediatric cochlear implant performance in patients with hearing loss secondary to bacterial meningitis. 2) To evaluate performance differences in patients with and without labyrinthitis ossificans (LO). STUDY DESIGN: Retrospective case review. SETTING: A large university-based multidisciplinary cochlear implant program. PATIENTS: Forty-nine patients with hearing loss from bacterial meningitis who received cochlear implants from 1991 to 2011. Thirty-nine patients had adequate data for analysis. INTERVENTION: Cochlear implantation with postoperative performance evaluation. MAIN OUTCOME MEASURE(S): Speech perception category (SPC). RESULTS: Nineteen (48.7%) patients had intraoperative evidence of LO. Fourteen patients (70.0%) without LO compared with seven (36.8%) with LO developed open-set speech after implantation. There was a trend toward better postimplant SPC outcomes in patients without LO that did not reach statistical significance (p = 0.17). The presence of LO negatively correlated with classroom placement (p < 0.05). Analysis of each group individually demonstrated statistically significant improvement in pre- versus postimplant SPC outcomes (p < 0.001). CONCLUSION: The presence of LO may negatively affect performance in pediatric patients receiving a cochlear implant for hearing loss secondary to bacterial meningitis.

Lyme disease: sudden hearing loss as the sole presentation.

BACKGROUND: Lyme disease is an uncommon tick-borne multisystemic infection caused by Borrelia burgdorferi. The most common clinical manifestation is erythema migrans. In this report, a very unusual presentation of this condition is described, in which sudden onset sensorineural hearing loss was the sole presenting symptom. METHODS: Case report and review of English-language literature. RESULTS: A patient presented with sensorineural hearing loss, with no other symptoms or signs. Acute Lyme infection was detected by laboratory tests. Magnetic resonance imaging showed signs of labyrinthitis of the same inner ear. After hyperbaric oxygen and systemic antibiotic treatment, the patient showed total hearing recovery, and magnetic resonance imaging showed complete resolution of the labyrinthitis. CONCLUSION: To our knowledge, this is the first reported case of Lyme disease presenting only with sensorineural hearing loss. Borreliosis should be considered as an aetiological factor in sensorineural hearing loss. Adequate treatment may provide total recovery and prevent more severe forms of Lyme disease.

Cerebral Ventriculitis Associated with Otogenic Meningoencephalitis in a Dog.

A dog was evaluated for rapidly progressive mentation change, ataxia, and tetraparesis. The dog's neurological status deteriorated drastically. It became comatose with bilateral mydriasis, and the pupillary light reflex was absent. An anti-inflammatory dose of methylprednisolone was administered, and temporary stabilization of neurological status was achieved. MRI findings were suggestive of ventriculitis and meningoencephalitis originating from the left tympanic cavity. A gadolinium leakage phenomenon was noted, likely resulting from severe damage to the blood-cerebrospinal fluid barrier during the inflammatory process. Analysis of the cerebrospinal fluid and materials in the left tympanic cavity further confirmed the diagnosis. Following surgical and antibiotic treatment, the dog recovered well with only a mild residual head tilt. Seven months after surgery, the dog had a recurrent infection of the left tympanic cavity without intracranial involvement. A second surgery led to an uneventful recovery, and the dog was clinically normal except for a mild head tilt 3 yr after the initial presentation. This is the first report describing ventriculitis associated with otogenic meningoencephalitis in dogs and a gadolinium leakage phenomenon displayed on MRI. The long-term outcome of ventriculitis-complicated otogenic meningoencephalitis in dogs could be satisfied with prompt diagnosis and treatment.

Effects of depletion of complement in the development of labyrinthitis ossificans.

HYPOTHESIS: Labyrinthitis ossificans results in part from the intense inflammatory response to Streptococcus pneumoniae cell wall components. Depletion of complement in Mongolian gerbils following induction of meningitis will reduce the degree of inflammation and subsequent cochlear fibrosis. STUDY DESIGN: Random prospective study. Histological evaluations were performed with the researcher blinded to the experimental group METHODS: S. pneumoniae meningitis was induced in 10 control and 18 experimental Mongolian gerbils with an intrathecal injection of the bacteria. Both groups of animals received treatment with penicillin. The experimental group was also treated with cobra venom factor to deplete complement in the animals. Three months after the induction of meningitis, the animals' temporal bones were harvested for histological evaluation. RESULTS: The decomplemented animals developed significantly less intracochlear fibrosis (P < .01). The mortality rate for the experimental group was 11% compared with 40% in the control group (P = .14). CONCLUSIONS: Reduction of the intense inflammatory response to the S. pneumoniae cell wall components in suppurative labyrinthitis secondary to bacterial meningitis reduced the degree of labyrinthitis ossificans.

Chronology of labyrinthitis ossificans induced by Streptococcus pneumoniae meningitis.

OBJECTIVE: Labyrinthitis ossificans consists of novel osteogenesis that fills the normally patent cochlear and vestibular lumen as an end-stage sequelae to various pathologies. This study was designed to establish the sequence of events and chronology of the osteoneogenesis and calcification. STUDY DESIGN: A prospective randomized double-blind study. METHODS: By using serial application of different colored fluorochromes, which deposit in newly forming bone, the timing of bone deposition and bone remodeling can be established. Labyrinthitis ossificans was induced in six groups (n = 5) of gerbils by an intrathecal injection of live Streptococcus pneumoniae. Group 1 received no fluorochrome labels, group 2 received one label, group 3 received three labels, and groups 4, 5, and 6 received four labels. The temporal bones were harvested after 2 weeks (group 1), 1 month (group 2), 3 months (group 3), 4 months (group 4), 6 months (group 5), and 12 months (group 6). RESULTS: Sixteen of the 25 animals that received labels developed ossification, demonstrated with fluorescent microscopy. In the animals that developed labyrinthitis ossificans, newly formed disorganized bone began calcifying as early as 3 weeks (label 1) after S. pneumoniae injection. Osteoneogenesis continued as evidenced by the presence of the other labels when first applied at 6 weeks (label 2), and 10 weeks (label 3). Ossification, calcification, and remodeling proceeded through a 12-month course, wherein a reduction of labels was present at 6 months and total disappearance by 12 months. CONCLUSIONS: The use of fluorescent stains in this animal model provides a means to establish a timeline of the ossification seen in labyrinthitis ossificans.

A clinical pathologic study of hearing loss in congenital cytomegalovirus infection.

Cytomegalovirus (CMV) infection is currently reported as the most common cause of congenital viral induced deafness. However, few systematic studies of the audiovestibular sequelae of this infection are present in the literature. A clinical pathologic study was conducted from 1976 to 1982 to evaluate this. Fifty-two pairs of infant and children's temporal bone studied demonstrated no evidence of CMV endolabyrinthitis even in the single case with evidence of extensive congenital CMV infection. Over 2,000 umbilical cord sera were screened to detect asymptomatic CMV infection with an incidence of 0.38% (and slightly greater than 1% when extrapolated to correct for the sensitivity of the method of detection) in a central Pennsylvania study population. No sensorineural abnormalities were detected in five asymptomatic children and 30 control children. However, three out of six (50%) infants, symptomatic at birth and followed to a mean age of 5.5 years, showed significant and progressive sensorineural loss and vestibular deficits.

Acute Streptococcus pneumoniae meningogenic labyrinthitis. An experimental guinea pig model and literature review.

OBJECTIVE: To create an experimental model of Streptococcus pneumoniae type 3 meningogenic labyrinthitis (a leading cause of deafness) similar to that in human disease. DESIGN: Cohort analytic study of guinea pigs that were inoculated intrathecally with varying dilutions of S pneumoniae type 3; the progress of the disease was compared with that in saline solution-inoculated control animals. SUBJECTS: Healthy adult Hartley guinea pigs without clinical evidence of middle ear disease that were conveniently sampled. INTERVENTIONS: Intrathecal inoculation of 10(4) to 10(6) colony-forming units of S pneumoniae type 3 into 13 guinea pigs; signs and symptoms of meningitis/labyrinthitis were observed for 15 days and compared with those in two saline solution-inoculated control animals. MAIN OUTCOME MEASURES: Morbidity--labyrinthitis, meningitis; end point--death. RESULTS: The 10(4) to 10(6) colony-forming units of S pneumoniae type 3 caused inflammation that extended from the meninges to the inner ear via the cochlear aqueduct within 3 days after inoculation; a dose of 10(7) killed animals within 12 hours after inoculation. Three of five animals that were inoculated with a 10(6) dose died 3 days after inoculation; two of three animals that were inoculated with a 10(5) dose lived to 15 days after inoculation. One of two animals that were inoculated with a 10(4) dose did not become infected. Inflammation extended to the middle ear by round-window destruction. Reactive bone formation simulated labyrinthine osteosclerosis. Observers assessed histologic slides "blindly." CONCLUSION: Guinea pigs can survive 15 days after intrathecal inoculation of a 10(5) dose, with morphologic features similar to those in human disease. This is an effective model for this study of meningogenic labyrinthitis.

Bacterial tympanogenic labyrinthitis, meningitis, and sensorineural damage.

Pathologic changes (sensorineural hearing loss, labyrinthitis, meningitis) can follow otitis media. Various macromolecular substances demonstrably enter the inner ear via the round window membrane, but its permeability to bacteria is less known. We inoculated Streptococcus pneumoniae type 7F bilaterally into the middle ears of two groups of chinchillas, with and without grafted round window membranes. Inner ears of inoculated animals were observed by light and electron microscopy. None with continuous grafts had labyrinthitis. Bacteria penetrated all three layers of nongrafted round window membranes and into all cochlear turns, entering Schuknecht's channels and following neuronal pathways; nerves were often degenerated, hair cells were damaged or missing, and the stria vascularis was edematous and hemorrhagic. The neural damage suggests a mechanism for the hearing loss that can follow otitis media. Absence of labyrinthitis and meningitis in grafted animals suggests a tympanogenic pathway for the bacteria.