Objectives: Biofilms, intracellular infection and NET production all play a role in chronic and r... more Objectives: Biofilms, intracellular infection and NET production all play a role in chronic and recurrent OM and need to be targeted if treatments are to be effective.
Petrous apicitis (PA) is a rare complication of otitis media. Gradenigo syndrome, with the classi... more Petrous apicitis (PA) is a rare complication of otitis media. Gradenigo syndrome, with the classic triad of otitis, deep pain, and abducens paralysis, is rarer still. The objective of this study was to determine if clinical presentation and management has changed over time. Retrospective chart review. Forty-four patients with PA over a 40-year period were studied. Symptoms, signs, and management outcomes were studied. Historical review, surgical anatomy and approaches, pathology, and microbiology, and an illustrative case are included as appendices. The classical Gradenigo triad of retro-orbital pain, otitis, and abducens palsy occurred in only six of 44 patients (13.6%). Over the 40-year observation period, those needing surgery has decreased. Antibiotics remain the primary treatment modality. Surgery is reserved for cases failing to respond to antibiotics. One of the 44 patients in this series died of his disease. Diagnosis and management algorithms based on these observations are...
Pseudomonas aeruginosa, a known biofilm-forming organism, is an opportunistic pathogen that plays... more Pseudomonas aeruginosa, a known biofilm-forming organism, is an opportunistic pathogen that plays an important role in chronic otitis media, tracheitis, cholesteatoma, chronic wounds, and implant infections. Eradication of biofilm infections has been a challenge because the biofilm phenotype provides bacteria with a protective environment from the immune system and antibiotics; thus, there has been great interest in adjunctive molecules that may inhibit biofilm formation or cause biofilm dispersal. There are reports that D-amino acids may inhibit biofilms. In this study, we test the ability of various D-amino acids to inhibit P. aeruginosa biofilm formation in vitro. We evaluated the effect of D-alanine (10 mM), D-leucine (10 mM), D-methionine (10 mM), D-tryptophan (10 mM), and D-tyrosine (10 uM and 1 mM) on biofilm formation in two commonly studied laboratory strains of P. aeruginosa: PAO1 and PA14. Biofilms were grown in 24-well and 96-well tissue culture plates, documented photog...
Chronic, persistent infections complicate otologic procedures utilizing implantable devices such ... more Chronic, persistent infections complicate otologic procedures utilizing implantable devices such as cochlear implants or tympanostomy tubes. These infections are thought to be due to the establishment of microbial biofilms on implant surfaces. To address this issue, we hypothesized that surface charge modification may inhibit the formation of Pseudomonas aeruginosa biofilms on implant surfaces in vitro and in vivo. We evaluated the effect of surface charge modification on bacterial biofilm formation by assessing the effect of the surface charge on bacterial adhesion in vitro and bacterial persistence in vivo. To study the effect of surface charge in vitro, the surface wells in culture plates were modified using a layer-by-layer polyelectrolyte assembly method. Bacterial adherence was measured at 30-, 60-, and 120-minute intervals. To study the effect of surface charge modification in vivo, the surface of titanium microscrews was similarly modified and then surgically implanted into ...
Learning Objectives: 1. Understand the indications for use of HA cement for ossicular reconstruct... more Learning Objectives: 1. Understand the indications for use of HA cement for ossicular reconstruction. 2. Appreciate the surgical tips for successful application of HA cement to the ossicular chain.
the antero-lateral wall. Conservative management is usually successful, but surgical correction i... more the antero-lateral wall. Conservative management is usually successful, but surgical correction is sometimes indicated. This presentation will show some practical aspects of ET physiology that are relevant to surgeons, methods for evaluating ET function and a systematic approach for diagnosing pathology. Accurate diagnosis of ET disorders will lead to successful management and when appropriate, surgical indications will be clear.
Otology Neurotology Official Publication of the American Otological Society American Neurotology Society and European Academy of Otology and Neurotology, Sep 1, 2011
Some anatomists have reported more than 3 ossicles within the middle ear. The most widely discuss... more Some anatomists have reported more than 3 ossicles within the middle ear. The most widely discussed of these is the lenticular ossicle, which we now understand to be the lenticular process forming the distal tip of the long process of the incus. Another supernumerary ossicle, within the stapes tendon, has also been described by a number of anatomists. Here, we examine the history of this ossicle's discovery, the sources of confusion concerning its existence in humans, and its presence in some mammalian species. We also discuss the variability in the nomenclature of supernumerary ossicles for historical accounts.
The Mongolian gerbil is an easily maintained rodent which has been useful for investigations of t... more The Mongolian gerbil is an easily maintained rodent which has been useful for investigations of the middle and inner ear. The gerbil may be used as an animal model for otitis media and cholesteatoma. The purpose of this study was to describe the ultrastructure of the epithelial and subepithelial lining of the gerbilline middle ear. The middle ear of the gerbil is lined by an epithelial membrane which is similar in cell type to human and guinea pig middle ear mucosa. The major part of the middle ear is lined with simple, non-keratinizing squamous cells with or without microvilli. Ciliated and secretory cells were concentrated around the Eustachian tube orifice; additionally, ciliated cells were seen in two distinct bands extending posteriorly below the cochlea in the hypotympanum and above the cochlea toward the tensor tympani muscle. The subepithelial region consists of fusiform cells (fibroblasts or 'surface osteocytes') and collagen adjacent to bone. These cell types and their distribution further supports the use of the gerbil as a model for human disease.
Similarities were noted between the nature of inner ear damage produced by loud sounds and by ami... more Similarities were noted between the nature of inner ear damage produced by loud sounds and by aminoglycoside antibiotics. Since body temperature affects cochlear function and influences the effects of noise on the ear, a similar effect was predicted for the aminoglycoside, kanamycin. By environmentally elevating the body temperatures of preweanling mice to approximately 1 degree C above that of the normal adult, kanamycin ototoxicity was increased (an average 20.4 dB threshold elevation, vs. 9.3 dB for kanamycin injected mice reared at room temperature). Hyperthermia per se had no influence on auditory thresholds. This may be of relevance to humans with fever who are treated with aminoglycoside antibiotics.
Localized bone modeling in the middle ear is substance-P dependent. Processes of local bone model... more Localized bone modeling in the middle ear is substance-P dependent. Processes of local bone modeling and remodeling in the middle and inner ear lead to destructive processes such as otosclerosis and chronic otitis media. The cellular events associated with these processes are known, but the mechanisms of the control and activation of the involved cells are not. The authors hypothesized that one of the control mechanisms of local bone modeling is related to the action of a neuropeptide, substance-P and that capsaicin, which depletes substance-P, would block modeling in the gerbil model of adaptive bone modeling. One middle ear of each of 24 Mongolian gerbils was pressurized to 10 mmHg to induce adaptive bone modeling. Half of the animals were pretreated with capsaicin and half received vehicle alone. At the end of the 5-day experimental period, the bulla was studied histomorphometrically for osteoclastic and osteoblastic activity. Capsaicin pretreatment inhibited the percent of bone occupied by osteoclasts on the inner surface of the bulla and the rate of mineralization of bone on the outer surface of the bulla. It is likely that substance-P is a mediator of localized adaptive bone modeling in vivo. Processes of bone modeling and remodeling in the middle and inner ear may be under neural control.
The auditory systems of aging LP/J and A/J inbred mice were studied using electrocochleography (A... more The auditory systems of aging LP/J and A/J inbred mice were studied using electrocochleography (AP thresholds) and surface preparation cytocochleography. Both strains showed marked age-related auditory threshold elevation, the LP/J demonstrating more pronounced elevation with age than the A/J. Surprisingly, the cytocochleograms showed the opposite relationship: the A/J strain had more loss of hair cells than the LP/J. The elevation of AP thresholds of the LP/J mouse was far out of proportion to the expected auditory deficit on the basis of the cytocochleogram alone. Auditory deficits in the aging LP/J mouse must be due to factors other than anatomical loss of sensory cells.
Archives of Otolaryngology Head and Neck Surgery, Jun 1, 1986
The pressure produced by expanding aural cholesteatomas has been implicated as a causal factor in... more The pressure produced by expanding aural cholesteatomas has been implicated as a causal factor in the induction of osteoclastic resorption of adjoining bone. This concept is supported by observations of osteoclastic bone resorption produced by expansive tympanic implants. We induced osteoclastic bone resorption in gerbils with tympanic implants of autologous and homologous cartilage, silicone rubber, and Teflon, which exerted pressure only by forces of gravity and surface tension. We estimated that the pressure exerted by these implants ranged from 2.1 X 10(-3) to 8.0 X 10(-3) dynes/sq cm (1.6 to 6.0 mm Hg). These pressures are within the range of pressures known to be exerted by cholesteatomas.
Objectives/Hypothesis: The study sought to evaluate the effects of MeroGel (Medtronic Xomed Surgi... more Objectives/Hypothesis: The study sought to evaluate the effects of MeroGel (Medtronic Xomed Surgical Products, Jacksonville, FL) hyaluronic acid sinonasal implants by using a mouse model. We expected that this material would dissolve, elicit minimal inflammation, and leave intact mucosa. However, pilot data showed that MeroGel may be osteogenic. The present work focuses on the description and quantification of these bony changes. Study Design: Animal experiment. Methods: The effects of MeroGel were evaluated using sinonasal and calvarial implants in C57BL/6 mice. The calvarial experiments employed both light microscopy (bone histomorphometry) and fluorochrome labeling (mineral apposition). Each implant study was subdivided into normal control animals, sham-operated control animals, a foreign body control, and MeroGel implants. MeroGel was also placed within subcutaneous pockets remote from bone. All mice were killed 1 month after surgery. Both percentage of bone area within the sinonasal cavity and total calvarial bone area were quantified and compared. Fluorochrome images and the subcutaneous implants were examined qualitatively. Results: MeroGel placement engendered new bone formation within the nasal lumen of mice. Compared with normal control animals, sham-operated control animals, and a foreign body control, this increase was statistically significant. The calvaria from MeroGel-implanted mice were thickened as compared with normal animals, sham-operated control animals, and a foreign body control. Tetracycline labeling demonstrated mineral apposition along the dorsal and ventral surfaces of the calvaria and within enlarged marrow spaces. MeroGel placed subcutaneously did not engender bone formation. Conclusions: MeroGel, a unique esterified form of hyaluronic acid, induced bone formation within the sinonasal cavity and on the calvaria of mice implanted with it. Our experiments suggest that, when placed adjacent to traumatized, remodeling bone, MeroGel may have osteogenic potential.
... Courtney CJ Voelker 1 , Richard A. Chole 1 , 2 , 3. ... Arch Intern Med 2008; 168(14): 1522-1... more ... Courtney CJ Voelker 1 , Richard A. Chole 1 , 2 , 3. ... Arch Intern Med 2008; 168(14): 1522-1530 2 Popelka G R, Derebery J, Blevins N H. et al Preliminary evaluation of a novel bone-conduction device for single-sided deafness. ...
Objectives: Biofilms, intracellular infection and NET production all play a role in chronic and r... more Objectives: Biofilms, intracellular infection and NET production all play a role in chronic and recurrent OM and need to be targeted if treatments are to be effective.
Petrous apicitis (PA) is a rare complication of otitis media. Gradenigo syndrome, with the classi... more Petrous apicitis (PA) is a rare complication of otitis media. Gradenigo syndrome, with the classic triad of otitis, deep pain, and abducens paralysis, is rarer still. The objective of this study was to determine if clinical presentation and management has changed over time. Retrospective chart review. Forty-four patients with PA over a 40-year period were studied. Symptoms, signs, and management outcomes were studied. Historical review, surgical anatomy and approaches, pathology, and microbiology, and an illustrative case are included as appendices. The classical Gradenigo triad of retro-orbital pain, otitis, and abducens palsy occurred in only six of 44 patients (13.6%). Over the 40-year observation period, those needing surgery has decreased. Antibiotics remain the primary treatment modality. Surgery is reserved for cases failing to respond to antibiotics. One of the 44 patients in this series died of his disease. Diagnosis and management algorithms based on these observations are...
Pseudomonas aeruginosa, a known biofilm-forming organism, is an opportunistic pathogen that plays... more Pseudomonas aeruginosa, a known biofilm-forming organism, is an opportunistic pathogen that plays an important role in chronic otitis media, tracheitis, cholesteatoma, chronic wounds, and implant infections. Eradication of biofilm infections has been a challenge because the biofilm phenotype provides bacteria with a protective environment from the immune system and antibiotics; thus, there has been great interest in adjunctive molecules that may inhibit biofilm formation or cause biofilm dispersal. There are reports that D-amino acids may inhibit biofilms. In this study, we test the ability of various D-amino acids to inhibit P. aeruginosa biofilm formation in vitro. We evaluated the effect of D-alanine (10 mM), D-leucine (10 mM), D-methionine (10 mM), D-tryptophan (10 mM), and D-tyrosine (10 uM and 1 mM) on biofilm formation in two commonly studied laboratory strains of P. aeruginosa: PAO1 and PA14. Biofilms were grown in 24-well and 96-well tissue culture plates, documented photog...
Chronic, persistent infections complicate otologic procedures utilizing implantable devices such ... more Chronic, persistent infections complicate otologic procedures utilizing implantable devices such as cochlear implants or tympanostomy tubes. These infections are thought to be due to the establishment of microbial biofilms on implant surfaces. To address this issue, we hypothesized that surface charge modification may inhibit the formation of Pseudomonas aeruginosa biofilms on implant surfaces in vitro and in vivo. We evaluated the effect of surface charge modification on bacterial biofilm formation by assessing the effect of the surface charge on bacterial adhesion in vitro and bacterial persistence in vivo. To study the effect of surface charge in vitro, the surface wells in culture plates were modified using a layer-by-layer polyelectrolyte assembly method. Bacterial adherence was measured at 30-, 60-, and 120-minute intervals. To study the effect of surface charge modification in vivo, the surface of titanium microscrews was similarly modified and then surgically implanted into ...
Learning Objectives: 1. Understand the indications for use of HA cement for ossicular reconstruct... more Learning Objectives: 1. Understand the indications for use of HA cement for ossicular reconstruction. 2. Appreciate the surgical tips for successful application of HA cement to the ossicular chain.
the antero-lateral wall. Conservative management is usually successful, but surgical correction i... more the antero-lateral wall. Conservative management is usually successful, but surgical correction is sometimes indicated. This presentation will show some practical aspects of ET physiology that are relevant to surgeons, methods for evaluating ET function and a systematic approach for diagnosing pathology. Accurate diagnosis of ET disorders will lead to successful management and when appropriate, surgical indications will be clear.
Otology Neurotology Official Publication of the American Otological Society American Neurotology Society and European Academy of Otology and Neurotology, Sep 1, 2011
Some anatomists have reported more than 3 ossicles within the middle ear. The most widely discuss... more Some anatomists have reported more than 3 ossicles within the middle ear. The most widely discussed of these is the lenticular ossicle, which we now understand to be the lenticular process forming the distal tip of the long process of the incus. Another supernumerary ossicle, within the stapes tendon, has also been described by a number of anatomists. Here, we examine the history of this ossicle's discovery, the sources of confusion concerning its existence in humans, and its presence in some mammalian species. We also discuss the variability in the nomenclature of supernumerary ossicles for historical accounts.
The Mongolian gerbil is an easily maintained rodent which has been useful for investigations of t... more The Mongolian gerbil is an easily maintained rodent which has been useful for investigations of the middle and inner ear. The gerbil may be used as an animal model for otitis media and cholesteatoma. The purpose of this study was to describe the ultrastructure of the epithelial and subepithelial lining of the gerbilline middle ear. The middle ear of the gerbil is lined by an epithelial membrane which is similar in cell type to human and guinea pig middle ear mucosa. The major part of the middle ear is lined with simple, non-keratinizing squamous cells with or without microvilli. Ciliated and secretory cells were concentrated around the Eustachian tube orifice; additionally, ciliated cells were seen in two distinct bands extending posteriorly below the cochlea in the hypotympanum and above the cochlea toward the tensor tympani muscle. The subepithelial region consists of fusiform cells (fibroblasts or 'surface osteocytes') and collagen adjacent to bone. These cell types and their distribution further supports the use of the gerbil as a model for human disease.
Similarities were noted between the nature of inner ear damage produced by loud sounds and by ami... more Similarities were noted between the nature of inner ear damage produced by loud sounds and by aminoglycoside antibiotics. Since body temperature affects cochlear function and influences the effects of noise on the ear, a similar effect was predicted for the aminoglycoside, kanamycin. By environmentally elevating the body temperatures of preweanling mice to approximately 1 degree C above that of the normal adult, kanamycin ototoxicity was increased (an average 20.4 dB threshold elevation, vs. 9.3 dB for kanamycin injected mice reared at room temperature). Hyperthermia per se had no influence on auditory thresholds. This may be of relevance to humans with fever who are treated with aminoglycoside antibiotics.
Localized bone modeling in the middle ear is substance-P dependent. Processes of local bone model... more Localized bone modeling in the middle ear is substance-P dependent. Processes of local bone modeling and remodeling in the middle and inner ear lead to destructive processes such as otosclerosis and chronic otitis media. The cellular events associated with these processes are known, but the mechanisms of the control and activation of the involved cells are not. The authors hypothesized that one of the control mechanisms of local bone modeling is related to the action of a neuropeptide, substance-P and that capsaicin, which depletes substance-P, would block modeling in the gerbil model of adaptive bone modeling. One middle ear of each of 24 Mongolian gerbils was pressurized to 10 mmHg to induce adaptive bone modeling. Half of the animals were pretreated with capsaicin and half received vehicle alone. At the end of the 5-day experimental period, the bulla was studied histomorphometrically for osteoclastic and osteoblastic activity. Capsaicin pretreatment inhibited the percent of bone occupied by osteoclasts on the inner surface of the bulla and the rate of mineralization of bone on the outer surface of the bulla. It is likely that substance-P is a mediator of localized adaptive bone modeling in vivo. Processes of bone modeling and remodeling in the middle and inner ear may be under neural control.
The auditory systems of aging LP/J and A/J inbred mice were studied using electrocochleography (A... more The auditory systems of aging LP/J and A/J inbred mice were studied using electrocochleography (AP thresholds) and surface preparation cytocochleography. Both strains showed marked age-related auditory threshold elevation, the LP/J demonstrating more pronounced elevation with age than the A/J. Surprisingly, the cytocochleograms showed the opposite relationship: the A/J strain had more loss of hair cells than the LP/J. The elevation of AP thresholds of the LP/J mouse was far out of proportion to the expected auditory deficit on the basis of the cytocochleogram alone. Auditory deficits in the aging LP/J mouse must be due to factors other than anatomical loss of sensory cells.
Archives of Otolaryngology Head and Neck Surgery, Jun 1, 1986
The pressure produced by expanding aural cholesteatomas has been implicated as a causal factor in... more The pressure produced by expanding aural cholesteatomas has been implicated as a causal factor in the induction of osteoclastic resorption of adjoining bone. This concept is supported by observations of osteoclastic bone resorption produced by expansive tympanic implants. We induced osteoclastic bone resorption in gerbils with tympanic implants of autologous and homologous cartilage, silicone rubber, and Teflon, which exerted pressure only by forces of gravity and surface tension. We estimated that the pressure exerted by these implants ranged from 2.1 X 10(-3) to 8.0 X 10(-3) dynes/sq cm (1.6 to 6.0 mm Hg). These pressures are within the range of pressures known to be exerted by cholesteatomas.
Objectives/Hypothesis: The study sought to evaluate the effects of MeroGel (Medtronic Xomed Surgi... more Objectives/Hypothesis: The study sought to evaluate the effects of MeroGel (Medtronic Xomed Surgical Products, Jacksonville, FL) hyaluronic acid sinonasal implants by using a mouse model. We expected that this material would dissolve, elicit minimal inflammation, and leave intact mucosa. However, pilot data showed that MeroGel may be osteogenic. The present work focuses on the description and quantification of these bony changes. Study Design: Animal experiment. Methods: The effects of MeroGel were evaluated using sinonasal and calvarial implants in C57BL/6 mice. The calvarial experiments employed both light microscopy (bone histomorphometry) and fluorochrome labeling (mineral apposition). Each implant study was subdivided into normal control animals, sham-operated control animals, a foreign body control, and MeroGel implants. MeroGel was also placed within subcutaneous pockets remote from bone. All mice were killed 1 month after surgery. Both percentage of bone area within the sinonasal cavity and total calvarial bone area were quantified and compared. Fluorochrome images and the subcutaneous implants were examined qualitatively. Results: MeroGel placement engendered new bone formation within the nasal lumen of mice. Compared with normal control animals, sham-operated control animals, and a foreign body control, this increase was statistically significant. The calvaria from MeroGel-implanted mice were thickened as compared with normal animals, sham-operated control animals, and a foreign body control. Tetracycline labeling demonstrated mineral apposition along the dorsal and ventral surfaces of the calvaria and within enlarged marrow spaces. MeroGel placed subcutaneously did not engender bone formation. Conclusions: MeroGel, a unique esterified form of hyaluronic acid, induced bone formation within the sinonasal cavity and on the calvaria of mice implanted with it. Our experiments suggest that, when placed adjacent to traumatized, remodeling bone, MeroGel may have osteogenic potential.
... Courtney CJ Voelker 1 , Richard A. Chole 1 , 2 , 3. ... Arch Intern Med 2008; 168(14): 1522-1... more ... Courtney CJ Voelker 1 , Richard A. Chole 1 , 2 , 3. ... Arch Intern Med 2008; 168(14): 1522-1530 2 Popelka G R, Derebery J, Blevins N H. et al Preliminary evaluation of a novel bone-conduction device for single-sided deafness. ...
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