Joseph E. Dohar

Microbiology of Normal External Auditory Canal

Objectives To isolate and characterize bacteria and fungi from the healthy ear and to obtain susceptibility profiles on each bacterial isolate.

Topical ofloxacin versus systemic amoxicillin/clavulanate in purulent otorrhea in children with tympanostomy tubes.

Acute otitis media (AOM) in children with tympanostomy tubes in place typically presents with otorrhea (draining ear). Because therapy is not standardized, various topical and systemic antibiotics of unproven efficacy and safety have been used in this indication. This study compared the safety and efficacy of ofloxacin otic solution, 0.3% (OFLX) with that of Augmentin oral suspension (AUG) in pediatric subjects 1-12 years of age with tympanostomy tubes and acute purulent otorrhea. Subjects were randomized to receive 10d of OFLX, 0.25 ml topically bid, or of AUG, 40 mg/kg per day. Audiometry was performed in subjects > or =4 years of age. Overall cure rate for clinically evaluable subjects was 76% with OFLX (n = 140) and 69% with AUG (n = 146; P = 0.169). Overall eradication rates for OFLX and AUG were similar for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis and were superior with OFLX for Staphylococcus aureus and Pseudomonas aeruginosa (P<0.05 for both). OFLX had a greater overall pathogen eradication rate (96% vs. 67%; P<0.001). Treatment-related adverse event rates were 31% for AUG and 6% for OFLX (P<0.001). Neither treatment significantly altered hearing acuity. Topical ofloxacin 0.3% otic solution 0.25 ml bid was as effective and better tolerated than systemic therapy with Augmentin oral suspension 40 mg/kg per day in treating AOM in children with tympanostomy tubes.

Prostaglandin E2 inhibition of keloid fibroblast migration, contraction, and transforming growth factor (TGF)-β1–induced collagen synthesis

Keloid formation has been linked to aberrant fibroblast activity, exacerbated by growth factors and inflammatory mediators. Prostaglandin E2 (PGE2), synthesized from arachidonic acid by cyclooxygenases (COX) and synthases (PGES), acts as both an inflammatory mediator and fibroblast modulator. Although PGE2 has known antifibrotic effects in the lower airway, its role in dermal fibrosis in general, and keloid formation in particular, remains unclear. This study focused on: (1) the effects of PGE2 on keloid fibroblast migration, contraction, and collagen synthesis and (2) endogenous PGE2 synthesis in response interleukin‐1β. PGE2 decreased keloid fibroblast migration and contraction via an EP2/EP4–cAMP mechanism that disrupted actin cytoskeletal dynamics and reversed transforming growth factor‐β1–induced collagen I and III synthesis. Impaired fibroblast PGE2 production has been linked to lower airway fibrosis and recently to keloid formation. Here, we showed that interleukin‐1β stimulation leads to nuclear factor‐κB translocation to the nucleus, resulting in up‐regulation of COX‐2 and microsomal PGE2 synthase 1. Up‐regulation of COX‐2 in, and secretion of PGE2 by keloid fibroblasts are diminished compared with their normal fibroblast counterparts. We suggest that the antifibrotic effects of PGE2 during keloid formation are potentially diminished due to aberrant paracrine fibroblast signaling. Exogenous PGE2 may supplement decreased endogenous levels and inhibit keloid formation or progression.

Mucosal Biofilm Formation on Middle-Ear Mucosa in a Nonhuman Primate Model of Chronic Suppurative Otitis Media†

Background: An increased awareness of bacterial biofilms and their formation has led to a better understanding of bacterial infections that occur in the middle ear. Perhaps the best studied pathogen for its propensity toward biofilm formation is Pseudomonas aeruginosa, also the primary pathogen in chronic suppurative otitis media (CSOM).

Processing of adenoid and tonsil specimens in children: A national survey of standard practices and a five-year review of the experience at the Children's Hospital of Pittsburgh

The best means of pathologically examining routine tonsillectomy and adenoidectomy specimens in children remains controversial. Otolaryngologists fear missing an unsuspected diagnosis. However, the cost-effectiveness of microscopic analysis, given the rare incidence of unsuspected diagnosis, is questionable. If a significant pathologic diagnosis is missed, the medicolegal implications could be significant. A questionnaire was sent to 111 members of the American Society of Pediatric Otolaryngology. Additionally, we reviewed our experience at the Childrens Hospital of Pittsburgh for the 5-year span from 1989 to 1994 to determine our incidence of unsuspected pathologic diagnoses. Sixty-five questionnaires were returned (59% response rate). More than half (56%) of the respondents stated that microscopic analysis was routinely performed on all specimens, and 42% replied that only gross examination was performed, reserving microscopic examination for selected cases. Three respondents said that they discarded their specimens in the operating room. From March 1989 to October 1994, in 1985 children undergoing bilateral tonsillectomy and adenoidectomy at the Childrens Hospital of Pittsburgh, no significant pathologic diagnoses were found. Twenty-seven additional children who underwent only tonsillectomy between January 1991 and October 1994 were also reviewed. One lymphoma, suspected before surgery, and a glycogen storage disorder, not suspected before surgery, were diagnosed. Therefore, in a total of 2012 children, we found only one clinically significant unsuspected diagnosis. In conclusion, we found no national consensus governing the best way to examine routine adenotonsillectomy specimens in children. Given that unsuspected diagnoses are rare, reserving microscopic analysis for specific clinical indications may be both more cost-effective and medically feasible.

Repair of the tympanic membrane with urinary bladder matrix

To test urinary bladder matrix (UBM) as a potential treatment for tympanic membrane (TM) healing and regeneration.

Prostaglandin E2 differentially modulates human fetal and adult dermal fibroblast migration and contraction: implication for wound healing.

Cyclooxygenase‐2 is up‐regulated shortly after dermal injury and it has been shown to have important activity during the repair process. Its main product in the skin, prostaglandin E2 (PGE2), modulates both inflammatory and fibrotic processes during wound healing and partially dictates the overall outcome of wound healing. PGE2 signaling has been shown to be altered during fetal wound healing. This study was designed to examine the mechanism(s) by which PGE2 regulates fibroblast migration and contraction and to determine whether these mechanisms are conserved in fetal‐derived dermal fibroblasts. Fetal and adult dermal fibroblasts express all four PGE2 receptors. PGE2 inhibits fetal and adult fibroblast migration in a dose‐dependent manner through the EP2/EP4–cAMP–protein kinase A pathway. However, fetal fibroblasts appear to be refractory to this effect, requiring a 10‐fold higher concentration of PGE2 to achieve a similar degree of inhibition as adult fibroblasts. Inhibition of adult fibroblast migration correlated with disruption of the actin cytoskeleton. In contrast, PGE2 or a cAMP analog did not disrupt the actin cytoskeleton of fetal dermal fibroblasts. These findings were extended using a modified free‐floating, fibroblast‐populated collagen lattice (FPCL) contraction assay designed to measure fibroblast contraction. PGE2‐inhibited FPCL contraction by adult fibroblasts, but fetal fibroblasts exhibited higher rates of FPCL contraction and a blunted response to exogenous modulation by PGE2 or a cyclase activator (forskolin). These findings indicate that fetal dermal fibroblasts are partially refractory to the effects of PGE2, a major inflammatory mediator associated with dermal wound healing. This effect may have significant and specific relevance to the scarless fetal wound‐healing phenotype.

Treatment of Chronic Suppurative Otitis Media with Topical Ciprofloxacin

To date, only ofloxacin has been approved by the US Food and Drug Administration for treatment of ears with a nonintact tympanic membrane. The purpose of this study was to determine the safety and efficacy of topical ciprofloxacin hydrochloride in the treatment of experimental chronic suppurative otitis media caused by Pseudomonas aeruginosa infection in cynomolgus monkeys. Forty adult cynomolgus monkeys were divided into 4 equal groups, and their ears were challenged with P aeruginosa, drained for 3 weeks, then treated twice daily for 4 weeks with 1 of 4 randomly assigned agents: 1) ciprofloxacin, 2) saline, 3) Cortisporin, or 4) vehicle. The animals were followed up with auditory brain stem response testing, culture, otoscopy, and histopathology. Both ciprofloxacin and Cortisporin treatment resulted in a significantly more rapid rate of clearance of P aeruginosa as compared to treatment with saline (100% versus 20%). Eradication was not associated with resolution of otorrhea after a 4-week period of treatment. There were no significant changes in auditory brain stem response wave latencies for any of the treatment groups. Histopathologic data revealed that there was no statistically significant difference in the amount of outer hair cell loss for the ciprofloxacin group as compared to the control ear and other treatment groups. We conclude, therefore, that topical ciprofloxacin is not ototoxic and is effective in sterilizing the otorrhea, but does not promote resolution of the drainage, in this animal model.

Spontaneous regression of juvenile nasopharyngeal angiofibroma

There is debate concerning the natural history of juvenile nasopharyngeal angiofibromas, especially whether or not they can spontaneously regress. Often claimed, spontaneous regression has not been well documented. To our knowledge, this is the first report in which a biopsy-proven juvenile nasopharyngeal angiofibroma spontaneously resolved. A second, less well-documented case is discussed.

Ciprofloxacin 0.3%/dexamethasone 0.1% sterile otic suspension for the topical treatment of ear infections: a review of the literature.

The objective of this article is to review the literature related to ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension. A systematic literature search utilizing Medline was conducted to identify peer-reviewed articles related to safety and efficacy. A total of 47 publications were identified and reviewed herein. The literature supports the use of antibiotic/antiiflammatory combination ear drops in the treatment of both acute otitis externa and acute otitis media in pediatric patients with tympanostomy tubes. Ciprofloxacin/dexamethasone has been demonstrated as safe and effective with regard to clinical cures and microbiological eradication of pathogens in either disease with low treatment failure rates. Additionally, the literature also provides clear evidence for the contribution of dexamethasone when added to ciprofloxacin for the topical treatment of ear infections.