ABSTRACT
Neonatal lupus erythematosus (NLE) is a passively acquired autoimmune syndrome resulting from transplacental passage of maternal anti-Ro/SSA and/or anti-La/SSB antibodies to the fetus. Characteristic manifestations of NLE include transient dermatitis, hepatic and hematologic abnormalities and congenital heart block. Skin lesions in NLE resemble subacute cutaneous lupus erythematosus and typically consist of annular, erythematous, scaly plaques. Telangiectasias, vascular abnormalities resulting from dilation of superficial dermal vessels, may also affect the skin in a minority of patients. The etiology of telangiectasias in NLE is unknown, but disordered angiogenesis likely plays a role. Hemangiomas are a common disorder of angiogenesis frequently encountered in infancy. There have been no reported cases of neonatal lupus associated with the development of hemangiomas. We present a case of an infant diagnosed with NLE after manifesting classic dermatitis, hepatic and hematologic abnormalities who later developed mucocutaneous and visceral hemangiomas. We further postulate that disordered angiogenesis, possibly dysregulated production of vascular endothelial growth factor, may play a primary role in the development of these cutaneous vascular lesions in NLE.
Subject(s)
Hemangioma, Capillary/etiology , Pregnancy Complications/immunology , Telangiectasis/etiology , Adult , Anti-Inflammatory Agents/therapeutic use , Antibodies, Antinuclear/immunology , Female , Hemangioma, Capillary/drug therapy , Hemangioma, Capillary/pathology , Humans , Infant, Newborn , Infant, Newborn, Diseases , Liver Diseases/immunology , Liver Diseases/pathology , Lupus Erythematosus, Systemic/complications , Prednisolone/therapeutic use , Pregnancy , Ribonucleoproteins/immunologyABSTRACT
A retrospective study of 101 children who underwent tracheotomy at the Children's Hospital of Pittsburgh from 1993 to 1996 was performed. The following criteria were reviewed in each patient: age, gender, race, prematurity, weight during tracheotomy, presence of preoperative airway support, duration of tracheotomy, nature (emergent versus elective), tracheotomy tube size, reason for tracheotomy, accompanying medical diagnoses, chest x-ray (CXR) findings, surgical service, postoperative symptoms (up to 3 days), and operative mortality rate. Of these criteria, our results show that CXR-screenable complications occurred in patients who underwent emergent recannulation, as well as those who exhibited ventilatory distress (oxygen saturation level of <90%) and specific changes in postoperative symptoms. Pneumothorax developed after tracheotomy in 3 of the 101 patients; each had one of these risk factors. We conclude that CXR of all pediatric patients after tracheotomy may be unnecessary with the use of flexible endoscopy and screening restrictions that are both health-conscious and cost-effective.
Subject(s)
Postoperative Complications , Radiography, Thoracic , Tracheostomy/methods , Adolescent , Adult , Child , Child, Preschool , Cost-Benefit Analysis , Female , Humans , Infant, Newborn , Male , Postoperative Complications/economics , Radiography, Thoracic/economics , Retrospective Studies , Tracheostomy/economicsABSTRACT
OBJECTIVES: To isolate and characterize bacteria and fungi from the healthy ear and to obtain susceptibility profiles on each bacterial isolate. STUDY DESIGN: Prospective. METHODS: Specimens were collected from the external canals and cerumen of healthy subjects. Species-level identification was obtained by combining phenotypic and genotypic data. End-point minimal inhibitory concentration testing was performed using National Committee for Clinical Laboratory Standards recommended methods. RESULTS: One hundred sixty-four subjects were cultured. Seventeen canal and 16 cerumen specimens showed no growth. One hundred forty-eight cerumen specimens yielded 314 organisms, including 23 fungi. One hundred forty-seven canal specimens yielded 310 organisms, including 7 fungi. Of 291 bacteria isolated from cerumen, 99% were Gram-positive. Of 302 bacteria isolated from the canal, 96% were Gram-positive. Staphylococci were 63% of both the cerumen bacteria and the canal bacteria. Coryneforms represented 22% of the bacteria in cerumen and 19% in the canal. Turicellaotitidis was the primary coryneform isolated from both the canal and the cerumen. Streptococci-like bacteria were 10% from the cerumen, 7% from the canal. In both cerumen and canal, Alloiococcusotitis was more than 95% of the streptococci-like bacteria. Fifteen gram-negative organisms were isolated from the canal and cerumen, including four Pseudomonas aeruginosa strains. The percentages of Staphylococcus epidermidis isolates that had high-level resistance (> or =8 microg/mL) were as follows: to neomycin, 28% from cerumen and 11% from the canal; to oxacillin, 28% from cerumen and 25% from the canal; and to ofloxacin, 15% from cerumen and 19% from the canal. CONCLUSIONS: Turcellaotitidis and A. otitidis were present with a much higher frequency than previously described, lending evidence that they be considered normal otic flora. Corynebacterium auris, previously reported only in children, was isolated from normal adults.
Subject(s)
Ear Canal/microbiology , Adult , Cerumen/microbiology , Child , Fungi/isolation & purification , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/isolation & purification , Humans , Microbial Sensitivity Tests , Prospective StudiesABSTRACT
BACKGROUND: Scar formation and subglottic stenosis often cause health problems in surgical otolaryngology. However, fetal wounds demonstrate scarless healing. The underlying mechanism remains poorly understood. We isolated differentially expressed genes by comparison between nonwounded with wounded skin of fetal and adult rabbits. METHODS: Skin incisional wounds were made in fetal (21 to 23 days' gestation) and adult rabbits. Nonwounded and wounded skin were harvested 12 hours after surgery. Total RNA was extracted. By means of messenger RNA differential display, differentially expressed complementary DNA fragments were isolated, cloned, and sequenced. The expressed transcripts were verified by reverse RNA dot blot and semiquantitative reverse transcription and polymerase chain reaction. RESULTS: One complementary DNA tag that was induced in fetal skin wounds and repressed in adult skin wounds was isolated. The sequence of this complementary DNA (352 base pairs) encodes the messenger RNA for the E-prostanoid (EP) 4 receptor for prostaglandin E(2) (PGE(2)). The truly differential expression of the transcript was confirmed. In normal skin, the EP4 receptor messenger RNA levels were higher in adults than in fetuses. Twelve hours after wounding, the EP4 receptor transcript was remarkably induced in fetal skin wounds but repressed in adult skin wounds. CONCLUSIONS: Our study demonstrates the differential expression of the EP4 receptor messenger RNA in fetal and adult skin before and 12 hours after wounding. Our results suggest that prostaglandin E(2) is involved in the differential cellular responses and in the regulation of the intracellular signal transduction through its binding to EP4 receptor during fetal wound repair.
Subject(s)
Dinoprostone/physiology , Fetus/physiology , Receptors, Prostaglandin E/physiology , Skin/embryology , Up-Regulation , Wound Healing/physiology , Animals , Female , Gene Expression , Pregnancy , RNA, Messenger/metabolism , Rabbits , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
BACKGROUND/PURPOSE: Scars form as wounds heal in adult organisms. In addition to disrupting cosmetic appearance, scar tissue can cause significant morbidity, and even death if it blocks vital organ function. Previous work has established that fetal wounds, especially in early to midgestation, can heal without scarring. Because such inherent physiological mechanisms ultimately are under genetic control, a study was initiated to elucidate the differences in gene expression that produce scarless wound healing in the mammalian fetus but scarring in postnatal wounds. Reverse transcription polymerase chain reaction (RT-PCR) differential display (DD) was used to detect differentially expressed mRNA transcripts in a rabbit model of wound healing. METHODS: Adult and 21-day fetal full-thickness rabbit skin specimens from wounded and unwounded sites were harvested 12 hours postwounding. RNA extracted from the tissue was used as a template in DD reactions using anchoring and random primers to generate tissue-specific gene expression fingerprints. The over 2,000 resulting amplimers (gene transcripts) were screened for differential expression among the 4 types of specimens: fetal control (unwounded), fetal wound, adult control, and adult wound. Selected bands distinctly upregulated or downregulated in fetal wound lanes on the DD gels were excised, and the cDNA was extracted, reamplified, cloned into vectors, and sequenced. DD results were confirmed by limiting-dilution RT-PCR using sequence-specific primers. RESULTS: Differential display (DD) showed 22 amplimers that were significantly upregulated in all fetal wound samples as compared with little or no expression in fetal control, adult control, or adult wound tissues. Conversely, 5 transcripts were downregulated in the fetal wound specimens but highly expressed in the 3 comparison tissues. Reamplification of selected transcripts by PCR, followed by cloning and DNA sequencing, yielded 7 distinct sequences, each representing a gene expressed differently in fetal wound than in the other 3 tissues. A transcript that was downregulated in fetal wound showed very high sequence homology to part of the human gene for the eta subunit of the hetero-oligomeric particle CCT (the chaperonin containing T-complex polypeptide 1 or TCP-1). An upregulated amplimer showed significant DNA sequence homology to glycophorins A and B. One sequence was identified as 28S rRNA. The remaining 4 candidate sequences showed no significant homology to known genes, but 1 had high homology to expressed sequence tags of unknown function. CONCLUSIONS: With careful experimental design and proper controls and verifications, differential display of RNA expression is a potentially powerful method of finding genes that specifically regulate a particular physiological process such as fetal wound healing. No a priori knowledge of what genes might be involved, or why, is necessary. This study indicates that downregulation of a gene that codes for a chaperonin subunit and upregulation of several other genes may be involved in the striking scarless character of wound healing in the mammalian fetus. Results suggest the hypothesis that downregulation of the CCT chaperonin in fetal wound may inhibit the formation of myofibroblasts, a cell type that correlates highly with scarring in postnatal wound healing, by preventing the folding of sufficient alpha-smooth muscle actin to form the stress fibers characteristic of these cells.
Subject(s)
Chaperonins/genetics , Cicatrix/genetics , Gene Expression Regulation , RNA, Messenger/genetics , Wound Healing/genetics , Amino Acid Sequence , Animals , Base Sequence , Cicatrix/prevention & control , DNA, Complementary/genetics , Disease Models, Animal , Glycophorins/genetics , Humans , Molecular Sequence Data , Rabbits , Reverse Transcriptase Polymerase Chain Reaction/methods , Sequence Homology, Nucleic AcidABSTRACT
OBJECTIVES: To investigate the safety and efficacy of a topical combination of tobramycin and dexamethasone in a primate model of chronic suppurative otitis media (CSOM) and to explore the contribution of the added topical steroid for the treatment of CSOM. DESIGN: Blinded, randomized, placebo-controlled trial. SUBJECTS: Sixty juvenile cynomolgus monkeys randomized into the following 6 treatment groups of 10 monkeys each: 0.3% tobramycin (group 1), combined 0.3% tobramycin-0.1% dexamethasone (group 2), combined 1.0% tobramycin-0.33% dexamethasone (group 3), 0.1% dexamethasone (group 4), vehicle (group 5), and phosphate-buffered saline solution (group 6). INTERVENTIONS: Chronic suppurative otitis media was established by inoculating the right ear with Pseudomonas aeruginosa. After 4 weeks of drainage, animals were treated according to the group assignment with 3 drops twice daily for 7 weeks. Hearing thresholds were monitored with repeated auditory brainstem response testing (ABR), and clinical response was monitored with repeated otoscopic examinations and cultures throughout the study. Cytocochleograms were evaluated for quantification of outer hair cell loss. RESULTS: Rapid resolution of otorrhea and eradication of P aeruginosa occurred in all groups receiving tobramycin. The inclusion of dexamethasone accelerated the resolution of otorrhea and negative yields of cultures compared with tobramycin alone. Otorrhea and positive culture findings persisted in the groups not treated with topical antibiotic. Results of ABRs at 4 and 8 weeks and cytocochleograms for outer cell hair loss were not affected by drug administration. Perilymph samples collected at the end of the study showed no detectable tobramycin. CONCLUSIONS: Combined tobramycin-dexamethasone ear drops were safe and effective in the monkey CSOM model. Dexamethasone enhanced the efficacy of tobramycin.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Dexamethasone/administration & dosage , Otitis Media, Suppurative/drug therapy , Pseudomonas Infections/drug therapy , Tobramycin/administration & dosage , Administration, Topical , Animals , Anti-Bacterial Agents/pharmacokinetics , Anti-Inflammatory Agents/pharmacokinetics , Auditory Threshold , Chronic Disease , Cochlea/pathology , Dexamethasone/pharmacokinetics , Drug Evaluation , Ear, Middle/pathology , Evoked Potentials, Auditory , Glucocorticoids , Macaca fascicularis , Otitis Media, Suppurative/diagnosis , Otitis Media, Suppurative/microbiology , Otitis Media, Suppurative/pathology , Perilymph/chemistry , Pseudomonas Infections/microbiology , Pseudomonas Infections/pathology , Pseudomonas aeruginosa/isolation & purification , Random Allocation , Tobramycin/pharmacokineticsABSTRACT
Although laryngotracheoesophageal clefts are often found in association with other well-described anomalies, we know of no previous reported association with eosinophilic gastroenteritis, a disorder of unknown etiology characterized by eosinophilic infiltration of the gastrointestinal tract. We treated 2 children who had laryngeal clefts and eosinophilic gastroenteritis. Since the esophageal inflammatory changes found in eosinophilic gastroenteritis may persist despite aggressive therapy, management of the laryngotracheoesophageal clefts is more complicated. The diagnosis of eosinophilic gastroenteritis should not be overlooked in patients with laryngotracheoesophageal clefts and warrants prompt referral to a pediatric gastroenterologist.
Subject(s)
Eosinophilia/complications , Gastroenteritis/complications , Larynx/abnormalities , Child, Preschool , Eosinophilia/pathology , Esophagitis/complications , Esophagitis/pathology , Gastroenteritis/pathology , Humans , Infant , MaleABSTRACT
Cell therapy and bioengineering hold great promise as therapeutic approaches using cells and cell-derived factors to treat various pathologic or trauma-induced states. One possible application is the transplantation of cells into wounded tissue to help regulate tissue repair. Cells engineered for optimal wound healing may help to minimize scarring following surgery or to enhance the rate of healing of chronic wounds. The purpose of the current study was to determine the effect of a viral insert, the LacZ-bearing, first generation adenovirus AdRGD, on the survival of dermally transplanted murine skin allogenic fibroblasts. The LacZ insert facilitated quantitation of both cell survival and gene expression and was used here to measure viable cell number. In addition to bearing the LacZ marker, the AdRGD vector is capable of carrying therapeutic gene inserts, so this study tested the feasibility of gene therapy for wound healing. Murine skeletal muscle PP6 (i.e., Pre-Plate 6) myogenic stem cells served as an alternate donor cell type. Cells were labeled with the LacZ-bearing AdRGD adenovirus vector and injected (50,000 cells/site) into the dorsal skin of adult normal, immunocompetent mice as well as in immunodeficient SCID mice. Skin biopsies were taken on days 0, 1, 2, 3, and 7 post-transplant, and assayed for LacZ expression. Soon after transplant (day 1), cell numbers underwent a transient decrease, but by day 2 post-transplant they were present in appreciable numbers. Between days 2-7 post-transplant, both allogenic fibroblasts and PP6 myogenic stem cells maintained survivability in similar numbers. Further, survival of transplanted cell types was similar in both normal, immunocompetent as well as SCID mice during this time period. There were no signs of acute inflammation or rejection in any of the samples. This study shows that AdRGD-transduced cells are not immunogenic in the mouse skin model and the cells show similar survival for the first 7 days post-transplantation independent of the cell type or immunocompetence of the host.
Subject(s)
Fibroblasts/transplantation , Fibroblasts/virology , Gene Expression/immunology , Animals , Cell Survival/immunology , Cells, Cultured , Disease Models, Animal , Feasibility Studies , Immunocompetence , Immunocompromised Host , Immunohistochemistry , Injections, Intradermal , Keratins , Mice , Mice, Inbred C57BL , Mice, SCID , Sensitivity and Specificity , Skin/cytology , VimentinABSTRACT
Cell therapy is a widely applicable therapeutic approach using cells and cell elements, frequently from fetal or young animals, for their beneficial effects. This study evaluated the host response to and tolerance of transplanted fetal skin fibroblasts. Cultured fibroblasts from adult rabbit skin (autogenic and allogenic), 21-day fetal rabbit skin (allogenic), and adult pig skin (xenogenic) were labeled with a fluorescent vital dye CM-DiI, injected intradermally into the dorsal skin of adult rabbits at multiple sites and then biopsied over an 8-week period. Each cell type showed a biphasic distribution curve with an early phase (0 to 28 days) and a late phase (28 to 56 days). In the early phase, cells showed a rise and fall in total cell density (reflecting an increase and then a decrease in total cell number), followed by a slow decrease in cell density with cells still detectable at 56 days. Fetal cells showed the highest survival at the end of the study. None of the groups showed clinical or histologic signs of acute inflammation or rejection. This study demonstrated that (1) transplanted fibroblasts are well tolerated by an immunologically competent host, (2) CM-DiI-labeled cells are detectable in vivo for at least 8 weeks, and (3) fetal fibroblasts have a distribution and survival profile that is distinct from that of adult fibroblasts.
Subject(s)
Fetus/cytology , Fibroblasts/transplantation , Skin/cytology , Age Factors , Animals , Cell Division , Cell Survival , Cells, Cultured , Rabbits , Swine , Transplantation, Autologous , Transplantation, Heterologous , Transplantation, HomologousABSTRACT
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.
Subject(s)
Anti-Infective Agents/therapeutic use , Ofloxacin , Ofloxacin/therapeutic use , Otitis Media with Effusion/drug therapy , Tympanoplasty , Administration, Topical , Adolescent , Anti-Infective Agents/administration & dosage , Child , Child, Preschool , Female , Humans , Infant , Male , Ofloxacin/administration & dosage , Prospective Studies , Retrospective Studies , Treatment OutcomeABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/toxicity , Cochlea/drug effects , Cochlea/embryology , Hearing Loss, Sensorineural/chemically induced , Kanamycin/toxicity , Animals , Anti-Bacterial Agents/administration & dosage , Audiometry , Disease Models, Animal , Female , Hair Cells, Auditory, Inner/drug effects , Hair Cells, Auditory, Inner/pathology , Hearing Loss, Sensorineural/diagnosis , Injections, Intralesional , Kanamycin/administration & dosage , Pregnancy , Reference Values , Sheep , Temporal Bone/drug effects , Temporal Bone/pathologyABSTRACT
In comparison to the extensive study of skin wound healing, there have been few reports investigating mucosal wound healing. Our primary objective was to compare the natural progression of wound healing in airway mucosa to skin in a rabbit model. Split-thickness skin wounds and subglottic mucosal wounds created by drill injury were compared on days 0, 1, 3, 5, 7, 14 and 21 after injury. Histologic examination was performed by a veterinary pathologist blinded to sample identity. Subglottic wounds showed a 'fibrinous clot' overlying the epithelium, analogous to the fibrin crust in skin wounds. Re-epithelialization started on day 5 in the subglottic epithelium and was complete by day 14; fibroplasia and fibrosis in the lamina propria were present on days 7-21. This wound healing profile paralleled the skin epidermis and dermis, respectively. The epithelial changes, however, were temporally extended in the airway. Our secondary objective was to determine the effects of treating airway mucosa with a bioresorbable membrane, modified sodium hyaluronate and carboxymethylcellulose (modified HA/CMC), placed over the subglottic wounds of four rabbits after drill injury. Subglottic wounds treated with modified HA/CMC showed a more mature epithelium and less fibrosis on day 21. In this pilot study, the application of a bioresorbable membrane improved mucosal wound healing at both the epithelial and lamina propria levels. Clearly, a larger study must be performed to confirm this interesting observation.
Subject(s)
Larynx/pathology , Skin/pathology , Wound Healing , Absorption , Animals , Carboxymethylcellulose Sodium , Hyaluronic Acid , Larynx/injuries , Membranes, Artificial , Mucous Membrane/injuries , Mucous Membrane/pathology , Rabbits , Skin/injuriesABSTRACT
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.
Subject(s)
Anti-Infective Agents/administration & dosage , Ciprofloxacin/administration & dosage , Otitis Media, Suppurative/drug therapy , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , Administration, Topical , Animals , Chronic Disease , Disease Models, Animal , Drug Combinations , Humans , Hydrocortisone/administration & dosage , Macaca fascicularis , Neomycin/administration & dosage , Polymyxin B/administration & dosage , Treatment OutcomeABSTRACT
Open laryngofissure with posterior cartilage grafting is advocated by some as the main treatment for posterior glottic stenosis in children. Endoscopic arytenoidectomy has been tried and recommended for bilateral vocal cord paralysis in children, but little published experience exists in its use for the treatment of pediatric posterior glottic stenosis. We describe our experience with this technique in 11 children ages 2 to 12 years, 6 of whom were under the age of 5 years. Nine of 11 patients at the initial surgery were tracheotomy-dependent; 2 others had previous laryngofissure with cartilage grafting, but continued to suffer from severe airway limitations. Modified carbon dioxide laser arytenoidectomies resulted in decannulation in 5 of 9 children and marked improvements in the 2 children without tracheotomies, as documented by flow volume loops and symptoms. Endoscopic arytenoidectomy, in our experience, is not as successful as open techniques described in previously published series of children, and requires multiple procedures due to the regrowth of granulation tissue. However, endoscopic repair is a viable option for low-grade stenosis and does not preclude an open repair in the future. It is also useful as an adjunctive procedure to augment the repair from an open approach.
Subject(s)
Endoscopy/methods , Laryngostenosis/surgery , Arytenoid Cartilage/surgery , Child , Child, Preschool , Female , Glottis , Humans , Male , Tracheotomy , Treatment Outcome , Vocal Cord Paralysis/surgeryABSTRACT
PURPOSE: Fetal dermal repair is regenerative and scarless until middle to late gestation, when there is a transition to fibrotic repair. Fetal skeletal muscle and tendon undergo repair with fibrosis similar to the process in adults. This study addresses whether fetal mucosal healing is regenerative and scarless. METHODS: Anesthetized pregnant rabbits underwent laparotomy and controlled hysterotomy at 21 to 23 days' gestation (term is 31 days). A midline thyrotomy was made, followed by cricoidotomy and circumferential cauterization of the subglottic mucosa. A similar insult was applied to weanlings. The data were collected in 2 groups. One group was followed to term and killed at 4 weeks. A second group was killed after 6 days (30 days' gestation). The weanlings were killed at similar points. The larynges were harvested and processed for histological and morphometric analysis. RESULTS: Three litters were followed to term. Of these, 1 was not recovered; in the other two, 7 of 8 manipulated fetuses were found and 3 of 8 were viable. The fourth litter was harvested after 6 days; all 4 injured fetuses were recovered and viable. All animals in the fetal injury groups healed with complete regeneration of the airway mucosa. In contrast, weanlings injured post partum had mucosal inflammation, necrosis, and ulceration; squamous metaplasia and basal cell hyperplasia were also found. There were fibrosis, granulation tissue, and inflammation in the lamina propria; chondritis, cartilaginous necrosis, chondrolysis, and perichondritis were also found. CONCLUSIONS: Fetal airway mucosal healing is regenerative and, thus, scarless. This study provides further support for the thesis that skin and mucosa respond to injury similarly in both the developmental and postpartum stages, and that subglottic stenosis is reasonably thought of as the "hyperplastic scar" of the airway. These results have potential therapeutic applications for mucosal wound management.
Subject(s)
Fetus/surgery , Larynx/surgery , Wound Healing , Animals , Female , Glottis/embryology , Glottis/ultrastructure , Larynx/embryology , Larynx/injuries , Mucous Membrane/embryology , Mucous Membrane/ultrastructure , Pregnancy , RabbitsABSTRACT
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.
Subject(s)
Laryngostenosis/physiopathology , Wound Healing/physiology , Animals , Connective Tissue/injuries , Connective Tissue/physiology , Glottis/injuries , Laryngostenosis/pathology , Mucous Membrane/injuries , Mucous Membrane/physiology , RabbitsABSTRACT
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.
Subject(s)
Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Anti-Infective Agents/therapeutic use , Bacterial Infections/drug therapy , Drug Therapy, Combination/therapeutic use , Middle Ear Ventilation , Ofloxacin/therapeutic use , Otitis Media, Suppurative/drug therapy , Acute Disease , Administration, Oral , Administration, Topical , Amoxicillin-Potassium Clavulanate Combination/administration & dosage , Amoxicillin-Potassium Clavulanate Combination/adverse effects , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Audiometry , Child, Preschool , Drug Therapy, Combination/administration & dosage , Drug Therapy, Combination/adverse effects , Female , Humans , Male , Ofloxacin/administration & dosage , Ofloxacin/adverse effects , Otitis Media, Suppurative/microbiologyABSTRACT
Doxacurium was administered by titrated infusion to 14 pediatric patients for 4.7-12.3 days after laryngotracheal reconstruction to produce minimum spontaneous movement and less than five posttetanic movements of the first toe after stimulation of the posterior tibial nerve. Recovery was documented by stimulation of the ulnar nerve with 2 Hz for 2 s (train-of-four [TOF]) at intervals of 1 min and measurement of the ratio of the fourth to the first response (TOF ratio) at the adductor pollicis. During spontaneous recovery, the TOF ratio was between 0.4 and 0.7 for 0.6-3.3 h, mean (SEM) 2.2 (0.31) h. The TOF ratio equaled 1 between 4.7 and 23.0 h, mean (SEM) 11.0 (2.1) h after termination of doxacurium infusion. In six of the patients, weakness and decreased coordination were noted for a few days to weeks postoperatively. There were no complications related to impairment of upper airway function or ventilation in those patients who had recovery of neuromuscular transmission to the extent of TOF ratio equal to 1 prior to extubation or in those patients in whom weakness or lack of coordination was noted after tracheal extubation.
Subject(s)
Immobilization , Isoquinolines , Neuromuscular Nondepolarizing Agents , Child , Child, Preschool , Electromyography , Evoked Potentials , Humans , Infant , Intensive Care Units , Intubation, Intratracheal , Isoquinolines/adverse effects , Isoquinolines/pharmacokinetics , Larynx/surgery , Neuromuscular Junction/drug effects , Neuromuscular Junction/physiology , Neuromuscular Nondepolarizing Agents/adverse effects , Neuromuscular Nondepolarizing Agents/pharmacokinetics , Synaptic Transmission/drug effects , Time Factors , Trachea/surgery , Ulnar Nerve/physiologyABSTRACT
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 Children's 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 Children's 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.
Subject(s)
Adenoidectomy , Adenoids/pathology , Palatine Tonsil/pathology , Pathology, Surgical , Practice Patterns, Physicians' , Tonsillectomy , Child , Cost-Benefit Analysis , Diagnosis, Differential , Feasibility Studies , Glycogen Storage Disease/diagnosis , Glycogen Storage Disease/pathology , Hospitals, Pediatric/statistics & numerical data , Humans , Lymphatic Diseases/diagnosis , Lymphatic Diseases/pathology , Lymphoma/diagnosis , Lymphoma/pathology , Microscopy , Otolaryngology , Pathology Department, Hospital/statistics & numerical data , Pathology, Surgical/statistics & numerical data , Pennsylvania/epidemiology , Practice Patterns, Physicians'/statistics & numerical data , Retrospective Studies , Surveys and Questionnaires , United States/epidemiologyABSTRACT
The choice of antimicrobial agents used to treat Pseudomonas aeruginosa infections of the ear is quite empiric. Yet in spite of this, very little has been published examining susceptibility patterns of aural isolates of P. aeruginosa. Recently, increasing concern has emerged over the development of resistance to many of the commonly used ototopical preparations with activity against P. aeruginosa. This concern stems from the fact that these preparations have been in use for a long time, and P. aeruginosa is known to develop resistance fairly readily. We prospectively studied the susceptibilities of aural isolates of P. aeruginosa in 231 consecutive children who were seen in the outpatient Pediatric Otolaryngology Department at Children's Hospital of Pittsburgh during the years 1992 and 1993. The agents tested included neomycin, polymyxin B, colistin, and norfloxacin. We found that only 17.8% of the isolates were sensitive to neomycin, as opposed to > 95% for each of the other agents tested (polymyxin B, 99.6%; colistin, 97.4%; and norfloxacin, 98.3%). This difference proved to be statistically significant (p < 0.05). Given the concern of aminoglycoside-induced ototoxicity and the high rate of neomycin resistance, we believe that further investigation of other alternative ototopic agents with activity against P. aeruginosa is warranted.