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.

Labyrinthine fistula detection: the predictive value of vestibular symptoms and computerized tomography.

A retrospective case record study of 20 patients in Oslo operated on for chronic otitis media with labyrinthine fistula between 1986 and 1999 was performed in order to estimate the incidence of, and identify predictors for, labyrinthine fistulas. The incidence of fistula was 0.3 per 100 000, with a median age at diagnosis of 37 years. The median duration of chronic otitis media prior to labyrinthine fistula detection was significantly correlated with age at surgery. Subjective hearing loss (90%), otorrhoea (65%) and dizziness (50%) were presenting symptoms. Modified canal-wall-down mastoidectomy was performed in all patients. Preoperative hearing levels could not predict postoperative hearing outcome. Positive signs of fistula were found in only 4 patients (20%). Correspondingly, computerized tomography (CT) diagnosed the fistula in 11 patients (55%). The seven patients presenting without dizziness and with a negative CT scan and fistula test were characterized by lower age, absence of previous middle ear surgery, lower preoperative pure-tone thresholds for bone conduction and better hearing outcome after surgery. In conclusion, the identification of a younger group of patients presenting with fewer symptoms indicates that fistulas should be suspected in all patients undergoing surgery for chronic middle ear and mastoid disease.

Paediatric otolaryngology--disease profile and characteristics of children in outpatient surgery.

Data were collected from 178 consecutively operated children during a 6-week period at an Oslo hospital in order to study disease profile and routines for referral and treatment in outpatient otorhinolaryngologic surgery. Median time from referral to surgery was less than 4 months. The majority of the children subjected to operation for recurrent acute otitis media, tonsillitis or upper respiratory infections had suffered from the disease for 12 months or less. Obstructive symptoms were registered in 18% of the children. Hospital referrals and controls came mainly from ENT (ear, nose and throat) specialists or paediatricians. Significantly more boys were subjected to surgery. Median age at the time of surgery was 4.2 years, and there was an equal distribution of pharyngeal and middle ear surgery. The numerous combinations of middle ear surgery reflect the non-specific treatment guidelines for otitis media.

Paediatric otolaryngology--a parental satisfaction study in outpatient surgery.

A parental satisfaction survey was administered to obtain information as to exactly how patients and their parents experience essential aspects of their treatment. The parents of 178 children who underwent ear, nose and throat (ENT) surgery completed a questionnaire on various aspects of treatment satisfaction during a 6-week period. Most of the respondents expressed overall satisfaction with the treatment. The factor analysis revealed three parental satisfaction factors. Accordingly, we interpreted the subscales as i) surgical staff and general treatment satisfaction, ii) nursing staff and general information satisfaction and iii) anaesthetic staff satisfaction. The internal consistency values of the subscales, as measured by Cronbach's alpha coefficient, were 0.86, 0.84 and 0.71, respectively. The three scores were mutually correlated; this correlation was significant (0.46-0.67). The duration of general anaesthesia and demographic factors had a small, but significant impact on the satisfaction subscores. In conclusion, the satisfaction study encourages improvement in the evaluation and administration of treatment.

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.

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.

Molecular determinants of (+)-tubocurarine binding at recombinant 5-hydroxytryptamine3A receptor subunits.

The 5-hydroxytryptamine type 3 (5-HT3) receptor is a transmitter-gated ion channel mediating neuronal excitation. The receptor native to neurons, or as a homopentameric assembly of 5-HT3A receptor subunits, displays a species-dependent pharmacology exemplified by a 1800-fold difference in the potency of (+)-tubocurarine [(+)-Tc] as an antagonist of the current response mediated by mouse and human receptor orthologs. Here, we attempt to identify amino acid residues involved in binding (+)-Tc by use of chimeric and mutant 5-HT3A subunits of mouse and human expressed in Xenopus laevis oocytes. Replacement of the entire extracellular N-terminal domain of the mouse 5-HT3A (m5-HT3A) subunit by that of the human ortholog and vice versa exchanged the differential potency of (+)-Tc, demonstrating the ligand binding site to be contained wholly within this region. Mutagenesis of multiple amino acid residues within a putative binding domain that exchanged nonconserved residues between mouse and human receptors shifted the apparent affinity of (+)-Tc in a reciprocal manner. The magnitude of the shift increased with the number of residues (3, 5, or 7) exchanged, with septuple mutations of m5-HT3A and human 5-HT3A subunits producing a 161-fold decrease and 53-fold increase in the apparent affinity of (+)-Tc, respectively. The effect of point mutations was generally modest, the exception being m5-HT3A D206E, which produced a 9-fold decrease in apparent affinity. We conclude that multiple amino acids within a binding loop of human and mouse 5-HT3A subunits influence the potency of (+)-Tc.

[Pediatric day surgery of the respiratory tract--indications and prioritization]. / Dagkirurgi i øvre luftveier hos barn--indikasjoner og prioritering.

Ear, Nose and Throat (ENT) procedures are the most common types of surgery in children and include adenoidectomy, tonsillectomy, myringotomy, ventilation tube insertion or combinations of these. In order to study disease profile and routines for referral and treatment in outpatient otolaryngologic surgery, data were collected from 178 children operated consecutively during a six-week period in 1998. Median time from referral to surgery was less than four months. The majority of children operated for recurrent acute otitis media, tonsillitis or upper respiratory infections had suffered from the disease for 12 months or less. Obstructive symptoms were registered in 18% of these children. Most patients were referred to the hospital by specialists in otolaryngology or paediatric medicine. Surgery was more common in male than female-children, and median age at the time of surgery was 4.2 years. There was an equal distribution of middle ear and pharyngeal surgery.

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.

Recurrent acute otitis media: the significance of age at onset.

In order to assess the relationship between recurrent acute otitis media (rAOM) and age at first acute otitis media (AOM) episode, a prospective cohort of 3754 Norwegian children born in 1992-1993 was followed from birth to 2 years. Recurrent acute otitis media was defined by the criterion of four or more episodes of AOM during a 12-month period. Approximately 5.4% of the children experienced rAOM before the age of 2. Furthermore, children whose first AOM episode occurred before the age of 9 months were at a significantly higher risk for developing rAOM compared to children whose first AOM episode was 10-12 months. In children who had the first ear infection during the first 9 months of life, one-quarter developed rAOM before the age of 2. Multiple logistic regression analysis adjusted for confounding showed that gender and a familial history of atopy were significantly associated with rAOM. In conclusion, the present study found an association between age at first AOM episode and the later subsequent AOM proneness. Additionally, both gender and a family history of atopy seemed to predispose towards otitis-proneness.

Early acute otitis media: determined by exposure to respiratory pathogens.

The purpose of the present study is to assess the relationship between early acute otitis media (AOM) and exposure to respiratory pathogens mediated by siblings and day-care. A prospective cohort of 3,754 Norwegian children born in 1992-93 was followed from birth through 12 months. One or more episodes of AOM had been experienced by 25% of the children before age one. Logistic regression analysis showed that siblings attending day-care is the most important risk factor for early AOM (ORadj = 1.9 (1.4-2.3)). The total number of children in the day-care setting is another determinant for early AOM (ORadj = 2.0 (1.4-2.6) in groups of 4 or more other children and ORadj = 1.3 (1.0-1.7) in groups of 1-3 other children as compared with those who are cared for alone). Siblings who attend day-care and the number of children in the child's own day-care setting are the most important determinants for AOM the first year of life.

[Serious streptococcal infections of the head and neck region]. / Alvorlige streptokokkinfeksjoner i øre-nese-halsområdet.

This article describes the four cases of serious infections caused by Streptococcus pyogenes in the head and neck. Three patients presented with invasive infections of the soft tissues in the neck and one with epiglottitis. Two patients fulfilled the criteria for toxic streptococcal shock syndrome. The incidence of severe streptococcal disease is increasing in Norway, which emphasizes the importance of an aggressive attitude when diagnosing and treating atypical throat infections.

[Secretory otitis. Treatment in the light of current knowledge]. / Sekretorisk otitt. Behandling i lys av nyere kunnskap.

Secretory otitis media refers to the presence of middle ear effusion behind an intact tympanic membrane without acute signs or symptoms. 10-20% of all children with acute otitis media subsequently develop secretory otitis media of at least eight weeks duration, but the disease can also be seen without previous existence of acute otitis media. Although spontaneous recovery is common, long-lasting secretory otitis may cause delayed language development. In the light of current knowledge about risk factors and treatment strategies for secretory otitis media, this paper discusses guidelines for the treatment of this condition.

[Acute and recurrent otitis media. Prevention and treatment in the light of current knowledge]. / Akutt og residiverende akutt otitis media. Profylakse og behandling i lys av nyere kunnskap.

Acute otitis media refers to a clinically identifiable infection of the middle ear with sudden onset and of short duration. By two years of age, approximately 40% of children have had at least one attack of acute otitis media. Of these, 5-10% subsequently experience recurrent infections. Evidence suggests that frequent attacks of acute otitis media may adversely affect neurocognitive and language development and necessitate repeated medical and surgical treatment. Efforts have been made to identify early risk factors associated with this proneness to otitis in order to give the affected children optimal medical care and prophylactic treatment. Based on existing literature, guidelines for prophylaxis and treatment of acute and recurrent acute otitis media are discussed in this paper.

Early acute otitis media and siblings' attendance at nursery.

To assess the relation between early acute otitis media and exposure to respiratory pathogens mediated by siblings and other children, a prospective cohort of 3754 Norwegian children born in 1992-3 was followed up from birth to 12 months. Of these, 25% had one or more episodes of acute otitis media during the first year. Results from multiple logistic regression analysis adjusted for confounding showed that siblings' attendance at daycare is the most important risk factor for early acute otitis media (adjusted odds ratio, ORadj = 1.9). The total number of children in the daycare setting is another determinant for early acute otitis media (ORadj = 2.0 in groups of four or more other children and ORadj = 1.3 in groups of one to three other children, as compared to those who are cared for alone). Having siblings in daycare outside the home and the number of children in the daycare setting are the most important determinants for early acute otitis media.

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.

Transient-evoked otoacoustic emissions. Helpful tool in the detection of pseudohypacusis.

The object of the present study was to demonstrate the use of TEOAEs for diagnosing pseudohypacusis. Thirty-four patients were investigated for suspected pseudohypacusis based on the case history and clinical and audiological findings. TEOAEs confirmed the diagnosis in all cases except four patients with a pre-existing organic hearing loss exceeding 25-30 dB HL. All the remaining 30 patients showed normal TEOAE responses except four of the ears in which final assessment revealed hearing threshold lower than 30 dB in the middle frequency region. The method can be time-saving when performed at the first consultation. With its element of surprise, the patient can be confronted with the existence of a functional hearing loss. This frequently results in marked threshold improvement on repeat pure-tone audiometry.