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Biomedical subjects

Joseph E Dohar

Publications and source records attributed to Joseph E Dohar.

18 recordsLinked to original sources
PubMed2006

Management of group A beta-hemolytic streptococcal pharyngotonsillitis in children.

Acute pharyngotonsillitis is one of the most common infections encountered by pediatricians and family physicians. According to the US Vital Health Statistics report, acute pharyngotonsillitis is responsible for more than 6 million office visits each year by children younger than 15 years of age and an additional 1.8 million visits by adolescents and young adults aged 15 to 24 years. Most children with acute pharyngotonsillitis have symptoms that can be attributed to infection with a respiratory virus, such as adenovirus, influenza virus, parainfluenza virus, rhinovirus, and respiratory syncytial virus. However, in approximately 30% to 40% of cases, acute pharyngotonsillitis is of bacterial etiology. Group A beta-hemolytic streptococci (GABHS) are responsible for most bacterial cases of acute pharyngotonsillitis, although other pathogens, such as Neisseria gonorrhoeae, Arcanobacterium haemolyticum, Mycoplasma pneumoniae, and Chlamydia pneumoniae, may be the causative agents in sporadic cases. Pharyngotonsillitis caused by these latter pathogens can sometimes be distinguished from that caused by GABHS by considering the patient's medical history in concert with the clinical presentation. In some cases, acute pharyngotonsillitis may have an idiopathic etiology. An accurate diagnosis of GABHS infection is important because it is the only common form of acute pharyngotonsillitis for which antibiotic therapy is definitely indicated. Antibiotic therapy can shorten the clinical course of GABHS pharyngotonsillitis, reduce the rate of transmission, and prevent suppurative and nonsuppurative complications, such as peritonsillar abscess and acute rheumatic fever. Although the threat of rheumatic fever is much lower for children in the United States than in developing nations, preventing rheumatic fever and the spread of disease is the primary goal of antibiotic therapy in GABHS pharyngotonsillitis treatment and a cornerstone of practice guidelines.

Acute Disease↗
PubMed2005

Identification of a pre-mRNA splicing factor, arginine/serine-rich 3 (Sfrs3), and its co-expression with fibronectin in fetal and postnatal rabbit airway mucosal and skin wounds.

Fibronectin (FN) is a multi-functional, adhesion protein and involved in multi-steps of the wound healing process. Strong evidence suggests that FN protein diversity is controlled by alternative RNA splicing; a coordinated transcription and RNA processing that is development-, age-, and tissue/cell type-regulated. We previously demonstrated that fetal rabbit airway mucosal healing is regenerative and scarless. Expression, regulation, and biological function of the FN gene and various spliced forms in this model are unknown. Airway and skin incisional wounds were made in fetal (gestation days 21-23), weanling (4-6 weeks) and adult (>6 months) rabbits. Non-wounded and wounded tissues were collected at 12 h (all age groups), 24 h and 48 h (weanling only) post-wounding. Expression profiles were obtained using mRNA differential display and cDNAs of interest were cloned, sequenced and validated by real-time PCR. Here, we report two rabbit cDNAs that showed similar expression patterns after wounding. One encodes a rabbit fibronectin gene, Fn1, and another shares a high sequence homology to a human pre-mRNA splicing factor, arginine/serine-rich 3 (Sfrs3), coding for a RNA binding protein, SRp20. Both Fn1 and Sfrs3 mRNAs were suppressed in fetal wounds but induced in postnatal wounds 12 h post-wounding. The increased levels of both Fn1 and Sfrs3 transcripts were sustained up to 48 h in weanling airway mucosal wounds. The augmentations of the two genes in postnatal airway mucosal wounds were more prominent than that in skin wounds, indicating that the involvement of Sfrs3 and Fn1 genes in postnatal airway mucosal wounds is tissue-specific. Literature provides evidence that SRp20 is indeed involved in the alternative splicing of FN and that the embryonic FN variants reappear during adult wound healing. A connection between the enhanced molecular activity of Sfrs3 and the regulation of the FN gene expression through alternative splicing during the early events of postnatal airway mucosal wound repair was proposed.

Animals↗
PubMed2005

Methicillin-resistant Staphylococcus aureus otorrhea after tympanostomy tube placement.

OBJECTIVE: To compare a retrospective cohort of nonhospitalized children with methicillin-resistant Staphylococcus aureus (MRSA) otorrhea with those with methicillin-sensitive S aureus (MSSA) otorrhea to determine the risk factors predisposing to MRSA otorrhea and the treatments used. DESIGN: Retrospective case-controlled series. SETTING: Tertiary pediatric care facility. PATIENTS: Seventeen children with MRSA otorrhea after bilateral myringotomy with tympanostomy tube insertion (BM&T) and 19 age- and sex-matched control subjects who demonstrated MSSA otorrhea. The average age at culture in MRSA patients was 52 months; in MSSA patients, 54 months. There were 8 boys and 3 girls in the MRSA group and 8 boys and 4 girls in the MSSA group. INTERVENTIONS: Oral, topical, and intravenous antimicrobial agents. MAIN OUTCOME MEASURES: Antibiotic exposure and history of otitis media and routine antibiotic administration (topical, oral, or intravenous). RESULTS: The following findings were statistically significant (P < or = .06, Mann-Whitney test): (1) longer duration of antibiotic treatment after BM&T for patients with MRSA vs those with MSSA; (2) increased number of episodes of acute otitis media before BM&T in patients with MRSA vs those with MSSA; and (3) increased number of courses of antibiotics after BM&T in patients with MRSA vs those with MSSA. CONCLUSIONS: Methicillin-resistant S aureus otorrhea is commonly seen as a community-acquired infection in otherwise healthy pediatric outpatients. Risk factors for development of MRSA otorrhea include the number of episodes of acute otitis media before BM&T and number of treatment courses and duration of antibiotic therapy after BM&T.

Acute Disease↗
PubMed2005

Fibroblast transplantation in the airway: implications for subglottic stenosis.

OBJECTIVE: Because subglottic stenosis (SGS) represents one of the most challenging pathologies confronting the pediatric otolaryngologist, our laboratory is investigating the role fibroblasts play in mucosal scar formation in the course of SGS development. Our objective is to establish cell transplantation into the subglottic mucosal wound bed as a viable tool for examining the cellular processes that underlie the development of SGS. DESIGN: A series of 2 animal experiments, with animals assigned to a control, vehicle-only, or cell-treated group. SETTING: John G. Rangos Sr Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pa. SUBJECTS: Twenty-six New Zealand white rabbits. This animal model has been well established in the study of SGS formation. INTERVENTIONS: Fluorescently labeled exogenous fibroblasts were transplanted into the injured subglottis of the rabbits. RESULTS: Exogenous fibroblasts derived from fetal and adult dermis and subglottic mucosa were successfully transplanted into the injured subglottic mucosa of adult rabbits. Transplanted fibroblasts survived into the latter stages of wound healing (at 14 and 21 days) and appeared to be associated with a mild inflammatory cell influx and active remodeling of the mucosal wound bed. CONCLUSION: Cell transplantation is a viable tool for the study of fibroblast activity in the mucosal wound bed.

Animals↗
PubMed2005

Mucosal wound healing in a rabbit model of subglottic stenosis: biochemical analysis of secretions.

OBJECTIVES: To build on work in laryngology and oral biology that suggests utility in the assay of secretions collected from wound sites as a predictive instrument to determine which infants will likely develop subglottic stenosis following endotracheal intubation and to document and describe the wound-healing process. DESIGN: Prospective, randomized design. INTERVENTION: Laser-induced subglottic injury was established in 3 rabbits. Secretions were collected from the subglottic region at 6 time points from days 4 to 21 following injury and from 4 uninjured control airways. The secretions were then subjected to enzyme-linked immunoassays for interleukin 1 beta and prostaglandin E2. SUBJECTS: Three adult New Zealand white rabbits. MAIN OUTCOME MEASURES: Interleukin 1 beta and prostaglandin E2 levels. RESULTS: Measurable amounts of both mediators were obtained. Furthermore, different temporal patterns of expression were observed with interleukin 1 beta, showing increased levels on days 4 to 18, and with prostaglandin E2, showing increased levels on days 7 to 18. These results concur with emerging data regarding the role of each mediator in the wound-healing process. CONCLUSION: Although in its infancy, the analysis of secretions collected from the site of injury in the subglottis may have utility in the management of patients following intubation-related trauma.

Animals↗
PubMed2005

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). OBJECTIVE: The aim of this study was to determine whether P. aeruginosa forms a biofilm in the middle ear in the setting of CSOM in a nonhuman primate model. METHODS: Cynomolgus monkeys underwent perforation of the tympanic membrane and inoculation of the middle ear with a known biofilm-forming strain of P. aeruginosa. The contralateral ear was used as an internal control and was neither perforated nor infected. At the end of the study period, both ears were irrigated to remove planktonic bacteria, and the middle ear mucosa was removed and examined ultrastructurally using scanning electron microscopy (SEM) for determination of the presence or absence of biofilm formation. MAIN OUTCOME MEASURE: The identification of middle ear biofilm containing rod-shaped bacteria. RESULTS: SEM revealed that P. aeruginosa formed bacterial biofilm in vivo on the middle ear mucosal surface, seen only in the infected ear. Interestingly, biofilm formation caused by cocci was also seen in both the experimental as well as the control ear. CONCLUSION: P. aeruginosa forms biofilms in the middle ear in CSOM in primates. To our knowledge, this is the first report of disease-associated bacterial biofilm in a nonhuman primate model of CSOM. Such a model lays a foundation for much needed study into the role of biofilms in the pathophysiology of CSOM. Should CSOM be caused by biofilms, which is uncertain at this time, development of novel strategies for treatment and prevention may be possible. The finding of both rods and cocci forming biofilms also warrants further investigation.

Animals↗
PubMed2005

Adult-fetal fibroblast interactions: effects on cell migration and implications for cell transplantation.

Wound healing is a complex process involving close cooperation between multiple cell types. During wound healing, fibroblasts are primarily responsible for synthesis of the replacement extracellular matrix. Fibroblast therapy is under investigation in this and other laboratories for its potential use to modulate the final outcome of the wound-healing process. This study addresses the potential interactions between transplanted and host fibroblasts, using a two-dimensional mixed culture model. Our results show that fibroblasts of two different phenotypes, fetal and adult, exhibit different speeds of in vitro migration. These migration speeds are conserved in mixed cocultures, suggesting that the migratory response is an intrinsic property of the fibroblast rather than a response to juxtacrine or paracrine signals. These results have relevance for cell-based therapies in that they demonstrate that donor fibroblasts of a different phenotype may at least partially retain that phenotype in the host environment and in the presence of endogenous fibroblasts.

Animals↗
PubMed2004

Lack of association between esophageal biopsy, bronchoalveolar lavage, and endoscopy findings in hoarse children.

OBJECTIVE: To determine the prevalence of esophagitis (based on esophageal biopsy results) and aspiration (based on bronchoalveolar lavage [BAL]) in children with hoarseness. DESIGN: Retrospective medical chart review spanning 24 months of 127 consecutive children (mean age, 6.9 years; range, 1.8-17 years) who presented with hoarseness to 2 attending otolaryngologists. SETTING: Tertiary care children's hospital.Intervention All subjects underwent direct laryngoscopy, rigid bronchoscopy with BAL, and rigid or flexible esophagoscopy with biopsy. MAIN OUTCOME MEASURES: The BAL result was considered positive if the number of lipid-laden macrophages was "moderate" or "large," and the esophageal biopsy result was considered positive if any 2 of the following 3 histologic criteria were present: basal cell hyperplasia, increased papillary height, and intraepithelial inflammatory infiltrate. Comparisons between subjective endoscopic findings and objective test results were made using the t test and contingency table analysis, where appropriate. RESULTS: Of the 127 children, 104 (82%) had vocal nodules; 53 (43%) had endoscopically visualized laryngitis; 36 (28%) had tracheobronchial inflammatory changes; 60 (47%) had abnormal esophagoscopy findings; 47 (37%) had a positive BAL result; and 38 (30%) had a positive esophageal biopsy result. There was no significant correlation between BAL and esophageal biopsy results (P = .11). The odds of having positive BAL or esophageal biopsy results were unaffected by the presence of vocal nodules; endoscopically visualized inflammation of the larynx, trachea, or esophagus; or symptoms or previous clinical history of gastroesophageal reflux disease. CONCLUSION: Positive esophageal biopsy and BAL results are prevalent among children with hoarseness, regardless of subjective upper aerodigestive tract endoscopic findings.

Adolescent↗
PubMed2004

Aural irrigation using the OtoClear Safe Irrigation System in children.

OBJECTIVE: To evaluate the safety and efficacy of the OtoClear Safe Irrigation System for removing cerumen from the external auditory canal in children. METHODS: Eligible subjects were 6 months-17 years of age with cerumen obstructing > or = 50% of the tympanic membrane (TM) from view (by otoscopy). Pneumatic otoscopy, tympanometry, and audiometry were performed followed by cleansing of the affected ear canal(s) with the OtoClear Safe Irrigation System and warm tap water. Otoscopy was performed after each wash of the canal. A curette or small alligator forceps was used to remove remaining cerumen if necessary. Tympanometry and audiometry were repeated after all procedures were completed. Telephone contact was made 1 week later regarding symptoms of acute otitis externa or any other problems. RESULTS: Eighteen children (28 ears) ages 1-10/12 to 11-2/12 years were entered. Four had previously had tympanostomy tubes. At entry, there was no visible TM in 19 ears, 5-10% visible TM in 5 ears, 20% in 1 ear, and 30-40% of the TM in 3 ears. The number of washes needed per ear was: 1 wash--16 ears, 2 washes--8 ears, 3 washes--1 ear, 4 washes--2 ears; washing was stopped in 1 ear because of pain. After irrigation, a curette or forceps was used in 6 ears. Following the procedures, > or = 95% of the TM was visible in 24 ears, and > or = 80% was visible in all ears. Six ears (4 children) with flat tympanograms at entry became normal after irrigation. On audiometry, a conductive loss in 2 ears at entry resolved after irrigation. The mean change in pure tone average (PTA) was -2.9 dB. Three subjects were noted to have hearing losses >5 dB at some frequencies which on review by audiologists were deemed non-significant. No perforations of the TM occurred. There were no reports of otitis externa or any other adverse events occurring after leaving the clinic. CONCLUSION: We found the OtoClear Safe Irrigation System to be safe and effective in our small sample of children. It was well tolerated in most and provided a non-traumatic method for the removal of obstructing cerumen.

Acoustic Impedance Tests↗
PubMed2004

Topical ciprofloxacin/dexamethasone otic suspension is superior to ofloxacin otic solution in the treatment of granulation tissue in children with acute otitis media with otorrhea through tympanostomy tubes.

OBJECTIVE: Comparison of topical ciprofloxacin/dexamethasone otic suspension (CIP/DEX) to ofloxacin otic solution (OFL) for treatment of granulation tissue in children with AOMT. STUDY DESIGN: 599 children aged >/=6 months to 12 years with AOMT of up to 3 weeks' duration were enrolled. Patients received either CIP/DEX 4 drops twice daily for 7 days or OFL 5 drops twice daily for 10 days. Granulation tissue severity was graded at clinic visits on days 1, 3, 11, and 18. RESULTS: Granulation tissue was present in 90 of 599 AOMT patients (15.0%) at baseline. CIP/DEX treatment was superior to OFL for reduction of granulation tissue at the day 11 visit (81.3% compared with 56.1%, P = 0.0067) and the day 18 visit (91.7% compared with 73.2%, P = 0.0223). Both topical otic preparations are safe and well tolerated in pediatric patients. CONCLUSION: CIP/DEX was superior to OFL in the treatment of granulation tissue in children with AOMT.

Administration, Topical↗
PubMed2003

Management of nontuberculous mycobacterial cervical lymphadenitis.

OBJECTIVE: To review the treatment and outcome of patients with nontuberculous mycobacterial (NTM) cervical lymphadenitis. DESIGN: Retrospective chart review. SETTING: Tertiary care children's hospital. PATIENTS: Thirty consecutive immunocompetent patients (median age, 32 months; age range, 11-147 months) diagnosed as having NTM cervical lymphadenitis over a 77-month period. INTERVENTIONS: Primary therapy for 34 foci of NTM cervical lymphadenitis in 30 children consisted of excisional biopsy (n = 8), incision and drainage procedures (n = 14), fine-needle aspiration biopsy (n = 7), observation only (n = 4), and antimycobacterial chemotherapy only (n = 1). MAIN OUTCOME MEASURES: (1) Time to cure, (2) recurrent adenitis, and (3) complications associated with therapy were determined for each therapeutic option. The average duration of follow-up was 32 months (range, 6-78 months). RESULTS: Nearly all patients (97%) were cured of their disease regardless of which therapeutic option was used. Excisional biopsy, while associated with transient marginal mandibular nerve injury in 1 patient, typically resulted in the most rapid resolution of disease. Observation alone did result in eventual cure, although the disease course was protracted. Simple incision and drainage without curettage was associated with prolonged postoperative wound discharge and hypertrophic scarring. CONCLUSIONS: A variety of therapeutic options were used in children with NTM cervical lymphadenitis. Resolution of infection was an eventual outcome regardless of treatment option, although duration of disease, potential for facial nerve injury, and incidence of hypertrophic scarring varied among the different treatments. An individualized management approach is recommended, with excisional biopsy as the preferred option when feasible.

Anti-Bacterial Agents↗
PubMed2003

Impact of transplanted fibroblasts on rabbit skin wounds.

OBJECTIVES: To determine the effect of injected fibroblasts on full-thickness cutaneous wounds and to distinguish between the properties of fetal vs adult fibroblasts. DESIGN: Full-thickness cutaneous wounds were created by incision in the skin of adult New Zealand white rabbits and treated with fluorescently labeled autogenic, allogenic, and xenogenic fetal and adult fibroblasts. Wound healing was evaluated by histologic analysis and tensiometry over time. SUBJECTS: A total of 9 New Zealand white rabbits with 24 wounds per animal were examined in this study. Groups of 3 animals were treated with different fibroblasts and euthanized at 7, 14, and 28 days after manipulation. INTERVENTION: Fibroblasts were labeled with a fluorescent dye (CM-DiI) and suspended in a hyaluronic acid gel. The cell-gel mix was used to treat full-thickness incisional wounds in rabbit skin. Imaging of CM-DiI determined the quantity and the migratory patterns of the transplanted fibroblasts present in the wounds. Tensiometry characterized the mechanical properties of the healed connective tissue. RESULTS: Transplanted fibroblasts exhibited good survival and migration patterns. Cell therapy increased the tensile strength of the wounds. Allogenic fetal and autogenic adult fibroblasts achieved similar effects. CONCLUSIONS: Cell therapy is a viable approach to significantly affect the course of normal cutaneous wound healing, and cell lines from genetically unrelated donors do not appear to be disadvantaged by a host immune response compared with autogenic cell lines.

Animals↗
PubMed2003

All that drains is not infectious otorrhea.

It has been said that, 'All that wheezes is not asthma.' Thus, is also so of otorrhea. Bacterial infection most often causes otorrhea which, in turn, generally responds to treatment with ototopical antimicrobial therapy. When it persists, non-infectious etiologies must be considered. Although allergic causes of otorrhea have been described in the literature, inhalant environmental allergens (Type I Allergy) causing eustachian tube dysfunction or ototopical drops, most notoriously neomycin containing formulations, causing contact dermatitis are those usually mentioned. Further, most reports of contact allergic reactions of the ear have involved the external auditory canal skin or pinna and have been attributed to non-medicinal triggers like shampoos and metals used in ear rings. A search of the literature failed to reveal a reported case of recurrent or chronic otorrhea without cholesteatoma due to an allergic reaction to the components of a tympanotomy tube (TT). Such a case is presented here.

Child, Preschool↗
PubMedDate not supplied

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.

Adult↗