Enhanced monocyte recruitment and delayed alternative macrophage polarization accompanies impaired repair following myocardial infarction in C57BL/6 compared to BALB/c mice.

Activation of the innate immune response following myocardial infarction (MI) is essential for infarct repair. Preclinical models of MI commonly use C57BL/6 mice, which have a type 1-dominant immune response, whereas other mouse strains such as BALB/c mice have a type 2-dominant immune response. We compared C57BL/6 and BALB/c mice to investigate whether predisposition towards a proinflammatory phenotype influences the dynamics of the innate immune response to MI and associated infarct healing and the risk of cardiac rupture. MI was induced by permanent coronary artery ligation in 12-15-week-old male wild-type BALB/c and C57BL/6 mice. Prior to MI, C57BL/6 mice had a lower proportion of CD206+ anti-inflammatory macrophages in the heart and an expanded blood pool of proinflammatory Ly6Chigh monocytes in comparison to BALB/c mice. The systemic inflammatory response in C57BL/6 mice following MI was more pronounced, with greater peripheral blood Ly6Chigh monocytosis, splenic Ly6Chigh monocyte mobilization and myeloid cell infiltration of pericardial adipose tissue. This led to an increased and prolonged macrophage accumulation, as well as delayed transition towards anti-inflammatory macrophage polarization in the infarct zone and surrounding tissues of C57BL/6 mice. These findings accompanied a higher rate of mortality due to cardiac rupture in C57BL/6 mice compared with BALB/c mice. We conclude that lower post-MI survival of C57BL/6 mice over BALB/c mice is mediated in part by a more pronounced and prolonged inflammatory response. Outcomes in BALB/c mice highlight the therapeutic potential of modulating resolution of the innate immune response following MI for the benefit of successful infarct healing.

Partial complementation of Sinorhizobium meliloti bacA mutant phenotypes by the Mycobacterium tuberculosis BacA protein.

The Sinorhizobium meliloti BacA ABC transporter protein plays an important role in its nodulating symbiosis with the legume alfalfa (Medicago sativa). The Mycobacterium tuberculosis BacA homolog was found to be important for the maintenance of chronic murine infections, yet its in vivo function is unknown. In the legume plant as well as in the mammalian host, bacteria encounter host antimicrobial peptides (AMPs). We found that the M. tuberculosis BacA protein was able to partially complement the symbiotic defect of an S. meliloti BacA-deficient mutant on alfalfa plants and to protect this mutant in vitro from the antimicrobial activity of a synthetic legume peptide, NCR247, and a recombinant human ß-defensin 2 (HBD2). This finding was also confirmed using an M. tuberculosis insertion mutant. Furthermore, M. tuberculosis BacA-mediated protection of the legume symbiont S. meliloti against legume defensins as well as HBD2 is dependent on its attached ATPase domain. In addition, we show that M. tuberculosis BacA mediates peptide uptake of the truncated bovine AMP, Bac7(1-16). This process required a functional ATPase domain. We therefore suggest that M. tuberculosis BacA is important for the transport of peptides across the cytoplasmic membrane and is part of a complete ABC transporter. Hence, BacA-mediated protection against host AMPs might be important for the maintenance of latent infections.

Pharmacological characterization of a rat 5-hydroxytryptamine type3 receptor subunit (r5-HT3A(b)) expressed in Xenopus laevis oocytes.

The present study has utilized the two electrode voltage-clamp technique to examine the pharmacological profile of a splice variant of the rat orthologue of the 5-hydroxytryptamine type 3A subunit (5-HT3A(b)) heterologously expressed in Xenopus laevis oocytes. At negative holding potentials, bath applied 5-HT (300 nM - 10 microM) evoked a transient, concentration-dependent (EC50 = 1.1+/-0.1 microM), inward current. The response reversed in sign at a holding potential of -2.1+/-1.6 mV. The response to 5-HT was mimicked by the 5-HT3 receptor selective agonists 2-methyl-5-HT (EC50= 4.1+/-0.2 microM), 1-phenylbiguanide (EC50=3.0+/-0.1 microM), 3-chlorophenylbiguanide (EC50 = 140+/-10 nM), 3,5-dichlorophenylbiguanide (EC50 = 14.5+/-0.4 nM) and 2,5-dichlorophenylbiguanide (EC50 = 10.2+/-0.6 nM). With the exception of 2-methyl-5-HT, all of the agonists tested elicited maximal current responses comparable to those produced by a saturating concentration (10 microM) of 5-HT. Responses evoked by 5-HT at EC50 were blocked by the 5-HT3 receptor selective antagonist ondansetron (IC50=231+/-22 pM) and by the less selective agents (+)-tubocurarine (IC50=31.9+/-0.01 nM) and cocaine (IC50 = 2.1+/-0.2 microM). The data are discussed in the context of results previously obtained with the human and mouse orthologues of the 5-HT3A subunit. Overall, the study reinforces the conclusion that species differences detected for native 5-HT3 receptors extend to, and appear largely explained by, differences in the properties of homo-oligomeric receptors formed from 5-HT3A subunit orthologues.

Frequency-following responses in the cat.

The frequency-following response was studied in five cats aged 1 week to 3 years. Animals studied had either monaural or binaural hearing. Responses were recorded differentially from vertex and circumaural electrodes to tonebursts at octave intervals from 0.5 to 4 kHz. Thresholds and dynamics of the responses with and without white-noise masking were investigated. Evidence was found to support the view that the cochlear microphonic makes a major contribution to the frequency-following response, while the double frequency-following response to the 0.5 kHz stimulus is neural.

Bilateral recording of early auditory evoked responses in the cat.

The brain-stem electric responses of the cat evoked by a short 4 kHz tone burst have been differentially recorded between vertex and both ipsilateral and contralateral ear electrodes. Six vertex-positive waves can be recognised in both recordings. Animals with hereditary unilateral anacusis were studied in order to avoid cross-stimulation of the opposite ear. The cochlear microphonic and summating potential can be readily recorded in young animals, occur simultaneously in both tracings, and show polarity inversion at the contralateral electrode. The later neural potentials have the same polarity and practically identical latencies in the ipsilateral and contralateral recordings, whilst the first three brain-stem waves show approximate polarity inversion and variable latency relationships in the two recording situations. It is concluded that none of the brain-stem waves represents electric activity from a discrete generator.

Air conduction thresholds after myringoplasty and stapes surgery: a conventional and high frequency audiometric comparison.

A comparison has been made of air conduction thresholds after myringoplasty and stapes surgery for otosclerosis in both the conventional (0.25 to 8 kHz) and high frequency (8 to 20 kHz) ranges. Significant threshold losses occurred in the high frequencies following both procedures. Threshold improvement was significantly greater at the lower frequencies following stapes surgery, while high frequency threshold deterioration was significantly less in the myringoplasty group. High frequency audiometry may prove to be a sensitive monitor of middle ear surgical techniques.

Subcutaneous bronchogenic anomalies.

Two cases of congenital anomalies, one cyst and one sinus, presenting in the suprasternal notch are reported. No communication with deeper structures was found at surgery, and histology was compatible with previous descriptions of subcutaneous bronchogenic cysts. The literature is reviewed, and the similarity between these lesions and many cases of branchial fistula is stressed.

Air conduction thresholds and secretory otitis media: a conventional and extra-high frequency audiometric comparison.

A comparison has been made of air conduction threshold changes up to 1 year after myringotomy, aspiration of middle ear fluid, and insertion of ventilation tubes in ten patients with bilateral and 12 with unilateral secretory otitis media (SOM). Pure tone air conduction thresholds have been analyzed in three frequency groups: low frequency (LF; 0.25 0.5, and 1 kHz), high frequency (HF; 2, 4, and 8 kHz), and extra-high frequency (EHF; 10, 12, 14 and 16 kHz). In the LF and HF ranges, significant improvement came during the first 24 hours after intubation, while in the EHF range, threshold lowering occurred gradually over the following 2 months. Possible explanations for these findings are discussed.

Audiometric results of TORP and PORP middle ear reconstruction.

The results of 70 middle ear reconstructions using either total or partial ossicular replacement prostheses are presented, the mean observation period being 45 months. Twenty-seven of the prostheses (39%) were extruded, this occurring as late as 72 months after surgery, and four (6%) were removed at reoperation. The surgical results when assessed by the magnitude of the air-bone gap are comparable to those of other series in the literature. However, postoperative air conduction thresholds remained high, and 23% of the patients are using hearing aids. The average air-bone gap for the frequencies 0.5, 1, and 2 kHz does not provide information on patients' everyday hearing level, and should no longer be employed as an index for assessing the functional results of middle ear surgery.

Tracing air flow and diagnosing hypopnoeas in normal subjects.

Hypopnoea is a type of sleep-related breathing disorder (SRBD), and the apnoea plus hypopnoea index (AHI) is usually computed to diagnose this condition. We introduce a new method to diagnose flow with internal thermistors located on the same sensors as we use to diagnose obstructive segments in patients with sleep-related breathing disorders. The aim of this study is to investigate whether internal thermistors are reliable for diagnosis of hypopnoeas. Fifteen volunteers participated in a prospective comparative study in healthy subjects without SRBD. We simultaneously measured minute ventilation by a pneumotachograph and indirectly air flow by internal thermistors in awake subjects was manually analysed from both the pneumotachograph and the internal thermistors. We found a close agreement between the different methods for percentage reduction in air flow both for the hypopnoea and the apnoea data. The mean difference between the percentage reduction in flow from normal breathing to hypopnoea measured by the pneumotachograph and the internal thermistors lying supine was 3.8% (SD 7.4). In the lateral position the corresponding figures were 1.0% and 4.6. This study in awake, normal subjects indicates that internal thermistors are as reliable as the pneumotachograph in diagnosing hypopnoeas and we believe that the reliability of this monitoring method is adequate for clinical use.

Granular cell tumor of the larynx in a 5-year-old child.

The youngest reported case of laryngeal granular cell tumor is presented together with transmission electron micrographs of the tumor cells. Whereas subglottic involvement is unusual in adults, a review of the literature reveals that three of the seven youngest patients (including the present patient) with laryngeal granular cell lesions had a subglottic tumor immediately below the anterior commissure.

Influence of adenoid hypertrophy on secretory otitis media.

The prognostic influence of adenoidectomy on the clinical course of chronic secretory otitis media (SOM) is reported after an observation period of five years in 166 children. Adenoidectomy was performed in connection with the first tubulation on the basis of concurrent symptoms of nasal obstruction, and resulted in a significant reduction in the need for repeated insertion of tympanostomy tubes in patients younger than eight years of age. The tubulation rate was also significantly reduced when adenoidectomy was performed in association with the first recurrence of SOM. This effect was, however, absent when the operation was performed at later stages, and both the otoscopic and audiological findings after five years revealed no significant differences between the adenoidectomy and nonadenoidectomy groups. Possible pathogenetic mechanisms leading to the development of SOM in the presence of large adenoids are discussed.

Acute mastoiditis: predictors for surgery.

To estimate the incidence of acute mastoiditis and identify predictors for mastoid surgery, a retrospective case record study of 38 children hospitalised for acute mastoiditis in Oslo from 1989 to 1998 was performed. Median age at diagnosis was 18 months and 13 (34%) of the children received mastoidectomy. Compared to the period 1970-1979, the incidence of mastoidectomy was significantly reduced. Only seven children (18%) had experienced acute otitis media prior to the current episode. Symptom duration of 6 days or more prior to hospitalisation and elevated white blood cell counts and C-reactive Protein were predictive for mastoidectomy ((OR = 5.0 (1.0-22.8), (OR = 24.5 (2.5-240) and OR = 10.5 (1-108.8)). Furthermore, total time from symptom onset to hospital discharge was significantly higher in children who received mastoidectomy. We suggest early referral to an otolaryngologic department in children suspected of acute mastoiditis.

Quality of care in pediatric daycare surgery: a cross-sectional study.

To provide information on how patients and their parents experience essential aspects of daycare otorhinolaryngologic surgery, a cross sectional questionnaire-based study on parental treatment satisfaction at the time of hospital discharge was performed. The main outcome measures were various aspects of treatment satisfaction in 178 consecutively children operated in a community hospital in Oslo, Norway. Overall treatment satisfaction was found. The factor analysis revealed three factors of parental satisfaction. Accordingly, we found the subscales interpreted as: (1) surgical staff and general treatment satisfaction; (2) nursing staff and general information satisfaction; and (3) anaesthetic staff satisfaction. The internal consistency of the subscales measured by the Chronbach's alpha coefficient were 0.86, 0.84 and 0.71, respectively. The three scores were significantly intercorrelated (0. 46-0.67). Parental treatment satisfaction was significantly influenced by demographic and anaesthetic factors. In conclusion, although outpatient pediatric otolaryngologic surgery aim at maximising the efficacy, overall treatment satisfaction was found in our study. Furthermore, the surgical, nursing and anaesthetic staff were identified as three separate quality dimensions.

Chronic secretory otitis media.

Of 242 children and teenagers treated surgically for chronic secretory otitis media in 1972, 212 presented for evaluation 5 years later. Although the pure-tone audiometric threshold was 20 dB HL or better in 87.7% of the ears, only 40.6% were judged to be otoscopically normal. The findings at the first myringotomy for insertion of tympanostomy tubes were of no prognostic value for the course of the disease, and the presence of characteristics of middle ear fluid at subsequent myringotomies varied unpredictably. Adenoidectomy performed at an early stage, and in the presence of nasal obstruction, resulted in a significant reduction in the need for re-insertion of tympanostomy tubes.

Otitis media: relationship to tonsillitis, sinusitis and atopic diseases.

In order to estimate the co-morbidity between ear infections and related childhood diseases, data about the occurrence of recurrent ear infections, tonsillitis, sinusitis and atopic diseases from a population based sample of 7992 Norwegian twins were analysed. Correlational results revealed two general clusters, one consisting of upper respiratory tract infections (URI), the other defined by the atopic diseases. Overall, associations between the diseases were greater in males. The sizes of the correlations within each subgroup of infections were moderate, but significant, ranging from 0.191 to 0.363. Similar results were found for the relationship within the subgroup of atopies, with correlations ranging from 0.134 to 0.466. The correlations between the infectious and atopic diseases were weak. Both ear infections and tonsillitis seemed to be predisposing factors for sinusitis. The relative risk of sinusitis among individuals with a history of ear infections was 3.4 (1.9-6.2) and 1.9 (1.2-3.0) for males and females, respectively. Ear infections conferred an increase in tonsillitis, estimated at 2.3 (1.6-3.0) and 2.0 (1.2-3.6) for males and females, respectively. In conclusion, the present study finds evidence for a common predisposition of upper respiratory infections as well as for atopic diseases, but only moderate correlation between the subgroups. Specifically, between ear infections and hay fever there was no covariation.

Benign lipoblastomatosis: a cervical tumor of children.

Two cases are presented by a rarely reported cause of a supraclavicular mass in the neck of young children. Benign lipoblastomatosis has usually been confused clinically with cystic hygroma. The literature is reviewed and the histological differential diagnosis discussed.

Hereditary deafness in the cat. An electron microscopic study of the spiral ganglion.

The spiral ganglion from white cats with hereditary deafness has been studied with the transmission electron microscope, and comparisons made with hearing animals at different ages. Ganglion cell loss occurs secondary to destruction of the organ of Corti, but only after the lapse of several months. Prior to neuronal loss, the type I ganglion cells lose their myelin sheaths and concurrently develop an increased content of neurofilaments. Type I neurons transform into type II through an intermediate type III stage. This process of neurofilamentous degeneration occurs slowly, and phagocytosis is therefore an inconspicuous feature.

Peripheral facial palsy and viral replication.

Significant levels of specific IgM and/or IgG antibodies against the cytomegalovirus (CMV) have been demonstrated in 64 (73%) of a consecutive series of 88 patients with acute peripheral facial palsy. Herpes varicella-zoster infection was serologically confirmed in 3 other cases. There were no detectable clinical differences between patients with and without immunological response to CMV antigens. The facial palsy and the CMV immunological response are contemporaneous, but these two phenomena need not necessarily be pathogenetically related.

Frequency specificity of the auditory brainstem responses in the cat.

The auditory brainstem responses evoked by click, noise-burst and tone-bursts have been recorded in the cat, and octave-wide derived bands obtained at 20 and 50 dB RL intensity levels. At near-threshold intensity both the 2 and 4 kHz tone-bursts are frequency specific, while the click and noise-burst ABR contain no contributions below 2 kHz. The principal contribution to the 1 kHz ABR comes from the 2-4 kHz band, while at 0.5 kHz almost the entire response is generated basally. Higher stimulus intensity produces a spread of activity into other bands. Low frequency cochlear function cannot be assessed by this technique.