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Biomedical subjects

J Jero

Publications and source records attributed to J Jero.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy of gene transfer through the round window membrane: an in vitro model.

The viral vector-transgene soaked gelatin-sponge method has been shown to be successful in mediating transgene expression across an intact round window membrane (RWM) in mouse in vivo. However, there are many confounding factors which make it difficult to evaluate the role of the RWM in gene transfer. We have created an in vitro model to test the feasibility of gene delivery through an intact RWM. The round window including the bony niche of a CD1 mouse was removed under an operating microscope and fixed with adhesive on the base of a petri dish through which a hole had been drilled. Toluidine blue was injected into the niche containing a hyaluronic acid ester sponge against the round window membrane. The niche was closed with a fascia. A plastic tube containing PBS was fixed on the opposite side, from where the samples were collected at different time points. The concentration of toluidine blue was evaluated spectrophotometrically. An adenoviral vector containing green fluorescent protein (GFP) marker gene was injected into the niche. Samples were collected from the opposite side at different time points. The presence of the vector was studied with GFP PCR. We also modulated the permeability of the RWM by treating it with clinically applicable detergents, histamine or silver nitrate. Silver nitrate and trichloracetic acid caused destruction of the surface epithelium of the RWM as shown by light microscopy. Both toluidine blue and adenoviral vectors passed through the RWM in a time-dependent fashion. RWM cells expressed GFP after Ad-GFP treatment. The permeability of the RWM was decreased after treatment with different detergents, histamine or silver nitrate. RWM offers an atraumatic route to the inner ear. Compared with more invasive gene delivery methods, this technique represents a safer and clinically more viable route of cochlear gene delivery.

Animals↗
PubMed2005

Acute complications of otitis media in adults.

OBJECTIVES: To establish the incidence, current treatment and outcome of adult patients with acute intratemporal and intracranial complications of otitis media (OM). DESIGN: A retrospective chart review with a sent questionnaire. SETTING: Tertiary referral centre, University hospital. PARTICIPANTS: Adult patients treated for acute intratemporal and intracranial complications of OM over the past 15 years (1990-2004) in the study hospital. MAIN OUTCOME MEASURES: Incidence, treatment and outcome of patients with intratemporal and intracranial complications of OM. RESULTS: Fifty patients aged 16-75 years were treated. The annual age-adjusted incidence of acute intratemporal and intracranial complications was 0.32/100 000. Forty-one (82%) of the complications were intratemporal and nine (18%) were intracranial. The ear disease behind the acute complication was acute otitis media (AOM) in 80% (40/50), chronic otitis media (COM) in 12% (6/50) and COM with cholesteatoma in 8% (4/50). Mastoiditis was complicated by subperiosteal abscess, labyrinthitis and facial paresis in 7% (3/41), 15% (6/41) and 32% (13/41) respectively. Mastoidectomy was performed on 56% (28/50) of the patients. Four (44%) of the intracranial complications were intracranial abscesses, four (44%) were meningitis and one (11%) was sinus thrombosis. Permanent hearing loss occurred in 13 (26%) patients and one patient died due to otogenic meningitis. CONCLUSIONS: Severe complications of the OM in adults are rare in Finland. The commonest cause is AOM rather than COM. Operative treatment is predominantly needed for intracranial complications and intratemporal abscesses. Complications of OM are still associated with considerable morbidity, and early recognition is most likely to form the basis for effective treatment.

Abscess↗
PubMed2001

New method for coating tympanostomy tubes to prevent tube occlusions.

OBJECTIVE: tympanostomy tube insertion is currently the most common surgical procedure requiring general anesthesia performed on children. Occlusion of the tube and prolonged otorrhea through the tube are typical problems associated with the use of middle-ear ventilation tubes. In this study, a new method for coating ventilation tubes is introduced that prevents occlusion of the tube lumen by granulation tissue, blood clot or pus. METHODS: human serum albumin (HSA) was used to coat standard tympanostomy tubes of different materials. Fibronectin, a typical protein in serum and exudates and one of the most adhesive glycoproteins, was used as a model representative of exudates of the ear. RESULTS: when compared with the binding on uncoated tubes, the binding of fibronectin on HSA-coated tubes was inhibited from 59 to 85%, depending on the tube material used. CONCLUSIONS: HSA-coating markedly reduced the binding of fibronectin on tube surfaces in vitro. The study shows the potential role of HSA-coating in preventing the adherence of foreign material to tympanostomy tubes and reducing tube occlusions.

Coated Materials, Biocompatible↗
PubMed2001

Cochlear gene delivery through an intact round window membrane in mouse.

Cochlear gene transfer studies in animal models have utilized mainly two delivery methods: direct injection through the round window membrane (RWM) or intracochlear infusion through a cochleostomy. However, the surgical trauma, inflammation, and hearing loss associated with these methods lead us to investigate a less invasive delivery method. Herein, we studied the feasibility of a vector transgene-soaked gelatin sponge, Gelfoam, for transgene delivery into the mouse cochlea through an intact RWM. The Gelfoam absorbed with liposomes and adenovirus, but not with adeno-associated virus (AAV), was successful in mediating transgene expression across an intact RWM in a variety of cochlear tissues. The Gelfoam technique proved to be an easy, atraumatic, and effective, but vector-dependent, method of delivering transgenes through an intact RWM. Compared with the more invasive gene delivery methods, this technique represents a safer and a more clinically viable route of cochlear gene delivery in humans.

Adenoviridae↗
PubMed2001

A surgical approach appropriate for targeted cochlear gene therapy in the mouse.

Therapeutic manipulations of the mammalian cochlea, including cochlear gene transfer, have been predominantly studied using the guinea pig as the experimental model. With the significant developments in mouse genomics and the availability of mutant strains of mice with well-characterized hearing loss, the mouse justifiably will be the preferred animal model for therapeutic manipulations. However, the potential advantages of the mouse model have not been fully realized due to the surgical difficulty of accessing its small cochlea. This study describes a ventral approach, instead of the routinely used postauricular approach in other rodents, for accessing the mouse middle and inner ear, and its application in cochlear gene transfer. This ventral approach enabled rapid and direct delivery of liposome-transgene complex to the mouse inner ear while avoiding blood loss, facial nerve morbidity, and mortality. Transgene expression at 3 days was detected in Reissner's membrane, spiral limbus, spiral ligament, and spiral ganglion cells, in a pattern similar to that previously described in the guinea pig. The successful access and delivery of material to the mouse cochlea and the replication of gene expression seen in the guinea pig demonstrated in this study should promote the use of the mouse in future studies investigating targeted cochlear therapy.

Animals↗
PubMed2001

The use of Preyer's reflex in evaluation of hearing in mice.

Preyer's reflex, the elicitation of startle response to auditory stimuli, has been widely used for the evaluation of hearing in rodents and other animals. Surprisingly, however, the sensitivity and specificity of Preyer's reflex in the assessment of hearing has not been adequately studied. The aim of this study was to investigate the utility of Preyer's reflex in the evaluation of auditory function in mice. Forty-six adult albino mice on an FVB background with variable hearing loss were used for this study. Two different methods for eliciting a Preyer's reflex were tested: a handclap and a sharp metallic sound. The reflex was considered positive when a rapid movement of the whole body of the animal was clearly noticed. Thereafter, the mice underwent auditory brain stem response (ABR) testing with broadband clicks. The presence or absence of Preyer's reflex was compared with the corresponding ABR thresholds. Five of the 46 animals studied (11%) showed a negative Preyer's reflex, while the remaining 41 animals demonstrated a positive Preyer's reflex. There was no difference between the abilities of the two different stimuli to elicit a Preyer's reflex. The click-evoked ABR thresholds in the test animals varied between 8 and 136 (mean 50) dB sound pressure level (SPL). Preyer's reflex was positive in all animals with an ABR threshold of < or = 76 dB SPL, but was absent in animals with an ABR threshold of > or = 81 dB SPL. Preyer's reflex is effective for identifying profound sensorineural hearing loss in experimental mice, but is insensitive for detecting less severe auditory dysfunction. For definitive hearing assessment, and for defining the hearing thresholds. objective electroacoustical methods such as ABR should be used.

Animals↗
PubMed2000

Otitis media as a sign of Wegener's granulomatosis in childhood.

Wegener's granulomatosis (WG) is a rare disease among paediatric patients. Chronic otitis media with or without facial nerve dysfunction is a known manifestation of the disease among adults. A case of a 15-year-old boy with WG, whose initial symptoms were acute otitis media and facial nerve paralysis, is presented. The otorhinolaryngological manifestations, as well as diagnostic and current treatment modalities in paediatric patients with WG, are discussed.

Administration, Oral↗
PubMed2000

Palatal myoclonus and clicking tinnitus in a 12-year-old girl--case report.

Palatal myoclonus is a rare neurological disorder of the soft palate and other oropharyngeal muscles, which causes clicking tinnitus. The latter is audible both to the patient and to an observer. The aetiology may be a brain stem lesion, and it is only rarely that a cause cannot be identified. The condition has been described in adults, but seldom in children. We present here a case of palatal myoclonus with distressing tinnitus in a 12-year-old girl and its successful treatment with electromyography (EMG)-guided injections of Clostridium botulinum toxin.

Anti-Dyskinesia Agents↗
PubMed2000

Clinical outcome of acute pneumococcal otitis media and serum antibody responses to pneumococcal pneumolysin and polysaccharides in children.

Serum antibody responses to pneumococcal antigens and their relationship to the clinical outcome were determined in a prospective study of 121 children with acute otitis media (AOM). Pneumococcus positive children with a pneumolysin response more often had a recurrence and middle ear effusion (MEE) after 1 month than did the non-responders (p = 0.005 and p = 0.04, respectively). All the children who responded to pneumolysin also had clinically strong symptoms and signs of AOM. Children who responded to pneumococcal polysaccharides developed otitis media with effusion within a 6-month follow-up period more often than did the non-responders (p = 0.005). The results of this study suggest that children with pneumococcal AOM and an antibody response to the intracellular pneumococcal protein pneumolysin behave clinically differently from children with an antibody response to polysaccharides.

Acute Disease↗
PubMed2000

Factors associated with the development of recurrent acute otitis media--the significance of choosing the right and accurate dependent and independent variables in the multivariate analysis.

The results of univariate and multivariate statistical analysis were compared in identifying predictive factors of the development of recurrent acuta otitis media (RAOM) after an initial episode of acute otitis media (AOM) in 121 children. Univariate correlations between the development of RAOM and potential risk factors were analysed, and variables at p < 0.10 were incorporated into the stepwise multiple logistic regression analysis. The comparisons between the univariate and multivariate analysis in identifying the predictive factors were made and the importance of changing the dependent variables in the multivariate analysis was analysed. It seems that univariate analysis is over-sensitive, but multivariate analysis is over-conservative in finding possible predictors of RAOM. Choosing the right and accurate dependent and independent variables in the multivariate analysis is extremely important, when this method is used.

Acute Disease↗
PubMed1999

Oral prednisolone is an effective adjuvant therapy for acute otitis media with discharge through tympanostomy tubes.

OBJECTIVE: To determine the efficacy of a short course of oral prednisolone as an adjuvant therapy for acute otitis media draining through tympanostomy tubes. STUDY DESIGN: In a randomized, double-blind, placebo-controlled study, children with acute discharge (<48 hours) through tympanostomy tubes received either prednisolone (2 mg/kg/d; n = 23) or placebo (n = 27) for 3 days. All children received amoxicillin/clavulanate (40/10 mg/kg/d) for 7 days. The children were examined daily at the study clinic until the drainage ceased. RESULTS: The median duration of otorrhea in the prednisolone group was 1.0 days (25% to 75% range, 1.0 to 2.0 days), compared with 3.0 days (25% to 75% range, 2.0 to 4.0 days) in the children receiving placebo (P <.001). The duration of otorrhea was </=2 days in 21 (91%) children in the prednisolone group, compared with 8 (30%) children in the placebo group (P <.001). CONCLUSIONS: Oral prednisolone appears to be modestly effective adjuvant therapy for acute otitis media with discharge through tympanostomy tubes in children. Further studies seem warranted to determine whether short-term use of steroids early during the course of acute otitis media would also reduce the duration of middle ear effusion in children with intact tympanic membranes.

Acute Disease↗
PubMed1999

Complement activation and expression of membrane regulators in the middle ear mucosa in otitis media with effusion.

The aetiopathogenesis of chronic otitis media with effusion (OME) in children is not yet fully understood. OME is characterized by metaplasia of the epithelium and accumulation of sticky, glue-like effusion in the middle ear containing different mediators of inflammation, including activation fragments of the complement system. Here we examined whether the fluid phase complement activation is reflected in the middle ear mucosa and how the mucosa is protected against the cytolytic activity of complement. Mucosal biopsies from 18 middle ears of children with a history of chronic OME were taken. The biopsies were analysed by immunofluorescence microscopy after staining for complement fragments iC3b/C3c, C3d and C9, and regulators membrane cofactor protein (MCP; CD46), decay-accelerating factor (DAF; CD55) and protectin (CD59). There was a strong staining for iC3b/C3c, and a weaker one for C3d and C9 on the surface of the middle ear epithelial cells of OME patients but not in controls without OME. MCP was expressed on the hyperplastic three to four outer cell layers of the epithelium, while CD59 was expressed throughout the middle ear mucosa. The results suggest a strong ongoing complement activation and consequent inflammation in the middle ear cavity. Unrestricted complement damage of the epithelial lining is prevented by the strong expression of MCP and CD59.

Antigens, CD↗
PubMed1998

Polymerase chain reaction-based detection of rhinovirus, respiratory syncytial virus, and coronavirus in otitis media with effusion.

OBJECTIVES: To study the association of human rhinovirus (HRV), respiratory syncytial virus (RSV), and human coronavirus infections in children aged 6 months to 12 years with otitis media with effusion (OME). To determine how long HRV RNA can be detected after HRV infection. METHODS: Middle ear effusion (MEE) samples collected at the time of tympanostomy tube placement from 100 children with OME were examined. Viral RNA was detected by reverse-transcriptase polymerase chain reaction. For HRV the results were compared with virus isolation in cell culture. In vitro studies of the persistence of HRV infectivity and RNA were conducted by combining approximately 10(5) median cell culture infectious doses of HRV with pooled MEE at 37 degrees C and assaying serial samples for 12 weeks. RESULTS: Virus RNA was detected in 30 children. HRV was detected by reverse-transcriptase polymerase chain reaction in 19 children with OME and by virus isolation in 5 children. RSV RNA was found in 8 and HCV in 3 children with OME. No dual viral infection was found. Bacterial pathogens were isolated from 35 MEE samples and were associated with viral RNA in 11 cases, most often with HRV (9 cases). Under in vitro conditions, HRV culture positivity declined rapidly (<2 days), but RNA was detectable for up to 8 weeks. CONCLUSIONS: These results suggest that virus infection, particularly HRV infection, either alone or concurrent with bacteria, is present in a larger percentage of children with OME than previously suspected. It remains to be determined how often the presence of viral RNA in MEE represents persistent RNA, ongoing viral replication, or recurrent infection.

Bacterial Infections↗
PubMed1998

Detection of rhinovirus, respiratory syncytial virus, and coronavirus infections in acute otitis media by reverse transcriptase polymerase chain reaction.

OBJECTIVE: To determine the frequencies of human rhinovirus (HRV), respiratory syncytial virus (RSV), and coronavirus (HCV) infection in children with acute otitis media (AOM). METHODS: Middle ear fluids (MEF) collected by tympanocentesis and nasopharyngeal aspirates (NPA) at the time of the AOM diagnosis were examined by reverse transcriptase polymerase chain reaction for HRV, RSV, and HCV RNA. PATIENTS: Ninety-two children aged 3 months to 7 years during a 1-year period. RESULTS: Virus RNA was detected in a total of 69 children (75%) and in 44 MEF samples (48%) and 57 NPA samples (62%) at the time of AOM diagnosis. HRV RNA was detected in both MEF and NPA in 18 (20%), in MEF alone in 4 (4%), and in NPA alone in 10 (11%). RSV was detected in both MEF and NPA in 12 (13%), in MEF alone in 5 (5%), and in NPA alone in 9 (10%). HCV RNA was detected in both MEF and NPA in 5 (5%), in MEF alone in 2 (2%), and in NPA alone in 9 (10%). Dual viral infections were detected in 5% of children. HRV and RSV were detected simultaneously in 2 MEF samples and in 2 NPA samples; RSV and HCV were detected in 1 NPA sample. Bacterial pathogens were detected in 56 (62%) MEF from 91 children. Viral RNA was detected in 20 (57%) MEF of 35 bacteria-negative and in 25 (45%) of 56 bacteria-positive MEF samples. No important differences in the risk of treatment failure, relapse, or occurrence of late secretory otitis media were noted between children with virus-positive and virus-negative MEF aspirates. CONCLUSION: These findings highlight the importance of common respiratory viruses, particularly HRV and RSV, in predisposing to and causing AOM in young children.

Acute Disease↗
PubMed1997

Prognosis of acute otitis media: factors associated with poor outcome.

Factors associated with poor outcome of acute otitis media (AOM) were analysed in 131 children aged 1/4 to 7 1/2 (median 2 1/2) years. After AOM, altogether 37 (28%) of the children had poor outcome: 15 children (12%) clinical failure (unimprovement or worsening of pre-treatment signs and symptoms within 2 weeks of onset of therapy) and 31 (24%) persistent middle ear effusion (MEE) > or = 1 month post-treatment. Of the different variables studied in multivariate analysis, age < 2 years (p < 0.01), history of allergic skin or respiratory symptoms (p = 0.02), > or = 6 h duration of pre-treatment earache (p = 0.01) and B. catarrhalis in MEE (p = 0.05) were associated with clinical failure. Children with previous adenotomy or unilateral AOM had no failures. Persistence of MEE at 1 month was associated with age < 2 years (p = 0.05), otitis proneness (p = 0.03), bilaterality of AOM (p < 0.01) and S. pneumoniae in MEE (p = 0.01) in univariate but not in multivariate analysis.

Acute Disease↗