An unusual solitary endobronchial pulmonary arteriovenous malformation in a 10 year-old child

Pulmonary arteriovenous malformations (PAVMs) are relatively rare in children. They may occur both as single isolated anomalies and, much more commonly, as one of many widely distributed arteriovenous malformations (AVMs) in other organs and anatomic locations such as the liver, brain, nose and spine. The latter phenotypically defines the condition known as Hemorrhagic Hereditary Telengiectasia (HHT). We report a case of a 10 year-old female with an isolated endobronchial right lower lobe PAVM. The patient's chest radiograph and fine-cut contrast-enhanced CT (CECT) of the neck and thorax were both uncharacteristically normal and, hence, non-diagnostic. Surgical lobectomy was the only means by which to both diagnose and treat this life-threatening condition. This unique case points out the dilemma facing the physician in such a case with only two management options neither of which is ideal: to either obtain a diagnosis with biopsy which is minimally invasive yet life-threatening due to the potential for fatal hemorrhage, or to perform a pulmonary lobectomy which entails removal of an entire lobe of the lung without a pre-operatively confirmed indication to justify the procedure. To our knowledge, this is the first reported case of a child with an endobronchial PAVM who did not carry the diagnosis of HHT, had normal chest radiography, and had a normal fine-cut CECT of the neck and thorax where such a management dilemma arose. This case points out that a high index of suspicion for PAVMs must be maintained despite normal chest radiography and CECT of the chest. In such cases, empiric lobectomy becomes the sole therapeutic and definitive diagnostic intervention. We hope that such a case published in the literature serves as a guide to physicians confronting similar circumstances as the rarity of such a constellation of variables precludes higher levels of evidence reporting such as a retrospective case series or prospective randomized controlled clinical trials.     

The effects of kanamycin injection into the fetal lamb cochlea

Mammalian auditory hair cells have minimal capacity for repair or regeneration after a variety of insults, including acoustic trauma and aminoglycoside exposure. Although fetal tissues have a greater potential for repair and regeneration than adult tissues, there have been no reported studies on fetal hair cell response to injury in mammals. The purpose of this research was to investigate the effects of local application of kanamycin on fetal lamb cochlear hair cells. Eleven fetal lambs in the early third trimester underwent kanamycin injection through the left round-window membrane. The right ear served as a control. Click-evoked compound action potentials (CAPs) were serially recorded in 8 fetuses. CAPs were observed in all control ears. None of the 8 kanamycin-injected ears had measurable CAPs on postoperative day 1. One kanamycin-injected ear demonstrated definite CAPs, beginning on postoperative day 6. Hair cells were found to be intact in 6 of 9 kanamycin-treated ears. Hair cells were missing only in animals that went into premature labor. The presence of intact hair cells despite the loss of measurable CAPs in kanamycin-perfused lamb cochleae was striking. This finding may indicate that the fetal auditory epithelium is relatively resistant to aminoglycoside injury or may be capable of prompt repair or regeneration. Further studies on the effects of aminoglycoside injury in the fetal cochleae seem to be warranted.     

Topical ofloxacin treatment of otorrhea in children with tympanostomy tubes.

OBJECTIVE: To determine the safety and efficacy of ofloxacin otic solution in the treatment of acute otorrhea in children with tympanostomy tubes. DESIGN: Multicenter study with an open-label, prospective ofloxacin arm and retrospective historical and current practice arms. SETTING: Ear, nose, and throat pediatric and general practice clinics and office-based practices. SUBJECTS: Children younger than 12 years with acute purulent otorrhea of presumed bacterial origin and tympanostomy tubes. INTERVENTION: Instillation of 0.3% ofloxacin, 0.25 mL, twice daily for 10 days in the prospective arm; review of medical records in the retrospective arms. MAIN OUTCOME MEASURES: The primary index of clinical efficacy was absence (cure) or presence (failure) of otorrhea at 10 to 14 days after therapy. The primary index of microbiologic efficacy (in the ofloxacin arm only) was eradication of pathogens isolated at baseline. Safety was evaluated in the ofloxacin arm only. RESULTS: Significantly more clinically evaluable ofloxacin-treated subjects were cured (84.4%; 119/141) than were historical practice subjects (64.2%; 140/218) (P< or =.001) or current practice subjects (70%; 33/47) (P< or =.03). All baseline pathogens were eradicated in 103 (96.3%) of 107 microbiologically evaluable ofloxacin subjects. Adverse events considered "possibly" or "probably" treatment related occurred in 29 (12.8%) of 226 ofloxacin-treated subjects. CONCLUSION: Ofloxacin is safe and significantly more effective than treatments used in historical or current practice for acute purulent otorrhea in children with tympanostomy tubes.     

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.     

Acquired subglottic stenosis--depth and not extent of the insult is key

In contrast to skin, mucosal wound healing has not been extensively studied. Subglottic stenosis (SGS) is an excellent model for such investigation. The main objective of this pilot study was to develop a chronic model of SGS in a small animal (i.e. rabbit). In so doing, a serendipitous observation was made that the development of SGS is directly related to depth of the injury and is independent of circumferential extent. Animals with deep injury (i.e. deep to the lamina propria, reaching the perichondrium), independent of age and circumferential extent, experienced respiratory obstruction resulting from edema and granulation tissue formation and died or had to be sacrificed in the acute period. This was in contrast to no risk of mortality in the more superficially injured group. Histology was used to characterize this model of SGS. In the mucosal epithelium, or mucosa, changes of inflammation, squamous metaplasia, basal cell hyperplasia, necrosis and ulceration were only seen acutely and total regeneration of the epithelium was achieved by the end of the study period. In contrast, changes within the lamina propria, including chronic inflammatory cellular infiltrates and fibroplasia, were lasting and resulted in fibrotic repair, not regeneration. These findings are quite similar to the healing events in skin and suggest that SGS is the mucosal equivalent of a 'keloid' or, perhaps more appropriately, a 'hypertrophic scar.' Likewise, cartilage degeneration and deformation were persistent markers of the chronic phase of healing. Like the lamina propria, the response to injury was reparative. Therefore, injury to the connective tissue is a critical component of development of SGS.     

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.     

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.     

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.     

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.     

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.