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Biomedical subjects

F L Rimell

Publications and source records attributed to F L Rimell.

At least 19 recordsLinked to original sources

Evidence of dysregulated cytokine production by sinus lavage and peripheral blood mononuclear cells in patients with treatment-resistant chronic rhinosinusitis.

BACKGROUND: Treatment-resistant chronic rhinosinusitis (CRS) imposes a clinical challenge. Its pathogenesis may be associated with dysregulated immune/inflammatory responses in the sinus. OBJECTIVE: To evaluate production of types 1 and 2 T cytokines (interferon gamma [IFN-gamma] and interleukin [IL] 5/IL-4, respectively) and regulatory/inflammatory cytokines (IL-10, IL-12, and IL-18) by sinus lavage (SL) cells and peripheral blood mononuclear cells (PBMCs) in patients with treatment-resistant CRS. METHODS: Sample SL cells and PBMCs obtained from 19 patients with treatment-resistant CRS were cultured with or without stimuli, and cytokine levels in the supernatant were measured using enzyme-linked immunosorbent assay. Control PBMC samples were obtained from 26 children. RESULTS: Chronic otitis media was found in 15 patients. Neutrophils and/or epithelial cells were dominant in SL cells. IFN-gamma, IL-12p40, and IL-10 (>100 pg/mL) were detected in SL cell cultures from 12, 9, and 8 patients, respectively. Production of IL-12p40 and IL-18 by SL cells correlated positively with phytohemagglutinin and IL-12p70 stimuli. In 12 patients, we detected IL-18 (>100 pg/mL) in SL cell cultures without stimuli, whereas PBMCs produced little IL-18, irrespective of stimuli. There was no correlation between cytokine levels produced by SL cells and PBMCs, except for IL-12p40 produced using IL-18. Decreased IFN-gamma production by PBMCs was observed in 6 patients with CRS compared with controls, but 4 of them had elevated IFN-gamma production by SL cells. Production of IL-12p40 by PBMCs was higher in 10 patients with CRS than in controls, and 7 of these patients had lower IL-10 production, resulting in an increased IL-12p40/IL-10 ratio. CONCLUSIONS: There is a role for locally produced regulatory cytokines in IFN-gamma production in the sinus in patients with treatment-resistant CRS. However, aberrant cytokine production patterns by PBMCs can be detected at high frequency in these patients, indicating that this can be used as a prognostic marker for patients with CRS.

Adolescent↗

Effects of the Clarion Electrode Positioning System on auditory thresholds and comfortable loudness levels in pediatric patients with cochlear implants.

OBJECTIVE: To evaluate the effects of using the Electrode Positioning System on psychophysical auditory thresholds, most comfortable loudness levels, and electric auditory brainstem response (EABR) thresholds in children with the Clarion version 1.2 cochlear implant. DESIGN: Retrospective analysis. SETTING: Academic tertiary care center. PATIENTS AND METHODS: Clinical records of a series of 25 children who received the Clarion version 1.2 cochlear implant at the University of Minnesota, Minneapolis, between January 1997 and August 1999 were examined. Measures evaluated were psychophysical thresholds (T-levels) and most comfortable loudness levels (M-levels) obtained at the 3-month posthookup audiologic evaluation and EABR thresholds obtained during implant surgery. Relevant threshold measures were available for 24 patients, 11 of whom had received the Clarion spiral electrode and electrode positioner (EP group) and 13 of whom had received the spiral electrode without positioner (non-EP group). The 3 measures (T-levels, M-levels, and EABR thresholds) were compared across groups. In addition, EABR thresholds were compared with T-levels and M-levels within groups. RESULTS: Mean T-levels and M-levels were significantly lower for the EP group than for the non-EP group, and interpatient variability for these measures was considerably smaller in the EP group. Electric auditory brainstem response thresholds were not significantly different for EP vs non-EP patients; however, EABR data were available for only a few non-EP patients. CONCLUSIONS: Use of the electrode positioner results in lower T-levels and M-levels in children with the Clarion version 1.2 cochlear implant, consistent with results of previous studies in adults, and reduces across-patient variability for these measures. It is unclear from the present data whether use of the electrode positioner systematically reduces intraoperative EABR thresholds.

Auditory Threshold↗

Real-time, cine magnetic resonance imaging for evaluation of the pediatric airway.

BACKGROUND: Standard magnetic resonance imaging (MRI) and computed tomographic (CT) modalities are limited in their ability to image dynamic organs. New real-time, dynamic, cine magnetic resonance imaging (CMRI) techniques have the potential to image moving structures. OBJECTIVE: We therefore investigated the feasibility of using CMRI techniques to dynamically image the human airway, to assess laryngeal and tracheal patency and function. METHODS: A cohort of 10 pediatric patients, 10 adult patients, and 10 normal volunteers underwent routine static MRI, as well as CMRI using a Siemens 1.5 T Vision system (Siemens, Erlangen, Germany). Patients also underwent endoscopic evaluation. Cine axial, coronal, and sagittal sequences of the larynx and trachea were obtained during quiet respiration, as well as during a variety of provocative maneuvers. RESULTS: CMRI readily demonstrated normal vocal cord mobility and tracheal stability in normal volunteers. Abnormal vocal mobility was easily appreciated using the CMRI imaging system. Similarly, dynamic effects of tracheomalacia were clearly demonstrated using CMRI. Dynamic extrinsic tracheal compression resulting from mass lesions or anomalous vasculature was also visualized using CMRI. CONCLUSIONS: Cine MRI of the airway has the potential to provide novel data regarding laryngeal and tracheal patency and function. This evolving modality may serve as a valuable adjunct to static MR and CT imaging, as well as endoscopy, in the assessment of the airway.

Adolescent↗

Cytokine production by sinus lavage, bronchial lavage, and blood mononuclear cells in chronic rhinosinusitis with or without atopy.

BACKGROUND: Chronic sinus inflammation may be determined partly by a balance of proinflammatory and counterregulatory cytokines and other mediators in the sinus. However, their mechanistic roles in chronic rhinosinusitis (CRS) are not well understood. OBJECTIVE: To evaluate production of proinflammatory (interferon gamma [IFN-gamma] and interleukin [IL] 12) and counterregulatory cytokines (IL-10 and IL-4) by sinus lavage (SL), bronchial lavage (BL), and peripheral blood mononuclear (PBMN) cells in patients with CRS. METHODS: We analyzed SL, BL, and PB samples obtained at surgery from 26 patients with CRS. Cytokine production was determined by culturing cells with or without stimuli. The results were evaluated in comparison with other inflammatory variables (cytologic findings, total protein, IgG, and lactose dehydrogenase), bacterial cultures, and clinical features. RESULTS: Production of IFN-gamma by SL cells was variable and did not correlate with other inflammatory variables, microbes grown, IL-10/IL-12p40 production by SL cells, or IFN-gamma production by BL or PBMN cells. Production of IL-4 by lavage cells was undetectable. None of 10 patients with elevated IFN-gamma production (>800 pg/10(6) SL cells with mitogen stimuli) had allergic rhinitis, whereas 12 of 16 patients with low IFN-gamma production (<500 pg/10(6) SL cells) had allergic rhinitis with positive reactivity to common aeoroallergens. There was no significant difference in other variables measured between low and high IFN-gamma production groups. CONCLUSIONS: Elevated IFN-gamma production by SL cells may indicate much less possibility of allergic rhinitis in patients with CRS, but other variables measured did not differ in patients with high or low IFN-gamma production by SL cells.

Adult↗

Interferon gamma levels in the sinus, ear, and airway in a rabbit sinusitis model induced by Bacteroides inoculation.

BACKGROUND: Previously, we found minimal bacterial dissemination and no evidence of systemic inflammation in a rabbit sinusitis model in which the left maxillary sinus was inflamed by Bacteroides inoculation with the ostium closed. However, we observed an increase in anti-Bacteroides IgG antibodies in the contralateral sinus, lower airway, and middle ear, with an apparent increase in interferon gamma (IFN-gamma) messenger RNA expression in the ear and sinus mucosa. OBJECTIVE: To evaluate how IFN-gamma production in the upper and lower airway is associated with localized bacterial sinusitis. DESIGN: Interferon gamma levels were measured in lavage solutions from the sinus, airway, and middle ear and in serum at 1, 2, 3, and 4 weeks following bacterial inoculation. SUBJECTS: The subjects were 6 rabbits at each time point. The controls were untreated (n = 5) and sham-operated (n = 4-5) rabbits at 2 and 4 weeks. INTERVENTION: Bacteroides fragilis (10(8) plaque-forming units) was inoculated into the left maxillary sinus. RESULTS: Interferon gamma levels in the ear and sinus were less than 0.2 microg/g protein in controls. Following bacterial inoculation into the left sinus, IFN-gamma levels increased up to 10-fold in both sinuses and even more in the middle ear at 3 weeks, independent of bacterial dissemination. Mean +/- SD IFN-gamma levels in the airway (0.3+/-0.28 microg/g protein in controls) were not altered by bacterial inoculation into the sinus. Serum IFN-gamma levels were very low (<0.05 microg/g protein) in most rabbits and were unchanged by bacterial inoculation. CONCLUSIONS: Interferon gamma levels increase in the ear and contralateral sinus in response to localized sinus inflammation, indicating concerted mucosal proinflammatory immune responses in the upper airway. Such responses may lead to the aseptic middle ear inflammation often observed in patients with chronic sinusitis.

Animals↗

Diagnosis and determination of the clinical significance of type 1A laryngeal clefts by gelfoam injection.

Laryngeal clefts are rare congenital disorders, classified by multiple different schemes. Type IA (Armitage) and type I (Benjamin and Inglis) laryngeal clefts exhibit absence or hypoplasia of the interarytenoid muscles with an intact cricoid ring. Submucous or "occult" clefts occur with intact mucosa but absent underlying cartilage and/or muscle. Children with a diagnosis of posterior laryngeal cleft often have other congenital anomalies or medical disorders, including gastroesophageal reflux, tracheomalacia, syndrome complexes, and developmental delay. These associated disorders often confuse the diagnostic picture, as they may contribute to or account for the presenting symptoms of a laryngeal cleft. We propose a method to help clarify the clinical significance of the laryngeal clefts in these patients, and determine which patients would benefit from cleft repair. Eight patients with type IA laryngeal clefts are presented who were treated with a "test dose" Gelfoam injection into the interarytenoid area at the time of endoscopic diagnosis. All patients exhibited clinical improvement, and 4 patients showed improvement on the postinjection videofluoroscopic swallow study as compared to preoperative studies. One patient has gone on to surgical repair of the cleft after multiple injections. Endoscopic Gelfoam injection at the time of diagnosis can both alleviate symptoms and provide clarification of the posterior laryngeal cleft's contribution to the clinical status of the patient in these often complex cases.

Adult↗

Bifid epiglottis.

Bifid epiglottis is a rare congenital defect that is often associated with other congenital annomalies. The most common defect associated with a bifid epiglottis are anomalies of the hands and/or feet (90%) while the most dangerous and potentially lethal anomaly if not recognized and treated are hypothalamic hamartomas and hypopituitarism (50%). A bifid epiglottis will often result in severe respiratory distress secondary to laxity of the cartilage and chronic aspirations, which may require surgical intervention. We present the case of a 10-week-old child who was sent for evaluation of stridor and aspiration. Office laryngoscopy demonstrated a true bifid epiglottis and further evaluation demonstrated a hypothalamic hamartoma consistent with Pallister-Hall syndrome. Management of our case as well as those previously presented in the literature are reviewed.

Child, Preschool↗

Cystic hygroma of the skull base.

Cystic hygroma is a benign developmental tumor formed by lymph vessels that occurs in 1 of 12000 individuals and presents most frequently in the head and neck. It is often difficult to manage because the tumor frequently envelopes nearby vital structures. Lesions that extend significantly above the hyoid are especially difficult to excise because of the complexity of achieving a complete excision. This article describes a series of 3 cases of cystic hygroma that presented in the head and neck and, on further investigation, were found to also involve the skull base. This anatomic location is exceedingly rare, and these 3 cases represent new and difficult challenges not previously discussed in the literature, to our knowledge.

Child, Preschool↗

Mandibular distraction osteogenesis in a neonate.

Children with craniofacial anomalies are predisposed to airway obstruction and frequently require airway intervention. Tracheotomy is performed when the airway obstruction is severe and refractory to other less invasive interventions. Tracheotomy is associated with significant morbidity, and there is a trend noted in the literature toward achieving earlier decannulation by the institution of definitive structural changes to the mandible. Mandibular distraction osteogenesis has been shown to alleviate airway obstruction in the pediatric population. We report a case in which mandibular distraction osteogenesis was successfully carried out in a neonate with acute airway obstruction at birth as a result of combined Pierre Robin sequence and Klippel-Feil syndrome. After 1 year, the patient still had an adequate airway with tolerable scarring and no neurologic sequelae.

Airway Obstruction↗

Fate of rigid fixation in pediatric craniofacial surgery.

The advantages of rigid fixation in adult craniofacial surgery are well documented, and implanted hardware is not routinely removed unless specifically indicated. There is a tendency, however, to remove hardware in children because of concerns with growth restriction, plate migration, and the lack of information on the fate of miniplates when used in pediatric craniofacial surgery. It has been our practice during the past decade not to remove hardware in children unless specifically indicated. Our study included a total of 121 procedures in 96 children, with an average age of 3.9 years and an average follow-up of 5 years. We placed 375 titanium plates and 1944 screws from 3 manufacturers. Complications encountered in children with titanium plates were as follows: 5 cases of delayed growth and 1 instance of restricted growth, 4 screw migrations (none intracranial), 9 palpable plates causing pain, 3 fluid accumulations over plates, 2 cases of meningitis, and 8 instances of plate and screw removal from the above complications. Twenty-two of 96 patients (23%) had a total of 27 complications from 121 procedures (22%). There were 6 cases in which pain precipitated removal of hardware, 1 case of an excessively mobile plate, and 1 case of documented growth restriction requiring removal; therefore our overall reoperation rate for plate removal was 8%, with no intracranial plate or screw migration.

Adolescent↗

Localized sinus inflammation in a rabbit sinusitis model induced by Bacteroides fragilis is accompanied by rigorous immune responses.

We evaluated inflammatory and immune responses against Bacteroides fragilis in a rabbit sinusitis model. Bacteroides was inoculated into the left maxillary sinus, and inflammatory (histology, cell number/cytology, lactose dehydrogenase, and apoptosis) and immune responses in the sinus, airway, and peripheral blood (PB) were determined for up to 4 weeks. In the inflamed sinus, the lactose dehydrogenase level was markedly elevated, with neutrophilic infiltration, severe tissue inflammation, and increased apoptosis. Low-grade tissue inflammation was present in the contralateral and sham-operated sinuses, but other parameters remained unchanged, and so did those in the airway and PB in the inoculated rabbits. Serum IgG antibody levels increased rapidly, were highest at 3 weeks, and began to decline at 4 weeks. Cellular immune responses (proliferation and interferon-gamma mRNA expression) against Bacteroides were detected in the PB of all inoculated rabbits. Vigorous immune responses against Bacteroides may have localized but failed to terminate inflammation in the sinus, indicating importance of microenvironmental factors.

Animals↗

Middle ear pathologic changes associated with chronic anaerobic sinusitis in rabbits.

OBJECTIVE/HYPOTHESIS: To study the histopathologic changes in association with the inflammatory/immune response present in the middle ears of a rabbit model of unilateral chronic anaerobic sinusitis. STUDY DESIGN: New Zealand white rabbits, two at each experimental time point. Normal rabbits and sham-operated animals served as controls. METHODS: Left maxillary sinusitis was induced by inoculating Bacteroides fragilis surgically after closure of the ostium. Cultures, lavages, and mucosa were harvested from bilateral middle ear and sinus cavities at 1, 2, 3, and 4 weeks following inoculation. Parameters analyzed include tissue for histopathologic study, immunoglobulin G antibody (IgG Ab) against B fragilis, and lactate dehydrogenase (LDH) levels in lavage samples, interferon gamma (IFN gamma) messenger RNA (mRNA) expression in mucosal tissue, and bacterial culture. RESULTS: Despite closure of the ostium of the left sinus, mild to moderate dissemination of B fragilis into the right sinus and left and right ears were observed in some but not all rabbits (2/8, 5/7, and 2/8, respectively). Histopathologic changes in the right sinus and middle ears were much less severe in contrast to the severe inflammatory changes in the left sinus. An immune response against B fragilis appeared to occur in the sinuses and ears bilaterally independent of bacterial dissemination, as evidenced by a rise of IgG Ab in lavage fluid and detection of IFNg mRNA. Neither control nor sham-operated animals had detectable levels of IFNg mRNA or IgG Ab. In B fragilis-inoculated rabbits, the magnitude of IgG Ab responses was equivalent in the right and left ear, independent of B fragilis dissemination; IgG Ab levels in the middle ear positively correlated to each other (P < .01) and to the levels in the sinuses (P < .01 and P < .01). LDH levels were closely associated with bacterial growth and degree of tissue inflammation. CONCLUSION: This reproducible model of chronic sinusitis provides an opportunity to study the middle ear infection and inflammatory/immune responses occurring with sinusitis. Our results indicate bilateral middle ear mucosal immune responses to an elicited sinus infection, independent of B fragilis dissemination.

Animals↗

Results of esophageal biopsies performed during triple endoscopy in the pediatric patient.

BACKGROUND: Endoscopic examination (direct laryngoscopy and bronchoscopy) is the method of choice for diagnosis of respiratory symptoms of unknown cause in children. However, gastroesophageal reflux is being recognized increasingly often as a cause of pediatric respiratory symptoms and is difficult to diagnose on the basis of findings from direct laryngoscopy and bronchoscopy. In cases in which gastroesophageal reflux was included in the differential diagnosis, we additionally performed esophagoscopy with esophageal mucosal biopsies. OBJECTIVES: To determine the feasibility, safety, and efficacy of routinely performing esophageal biopsies during triple endoscopy in children. METHODS: Twenty-four children ranging in age from 2 weeks to 10 years were referred for airway evaluation. Under general anesthesia, children underwent direct laryngoscopy and bronchoscopy and esophagoscopy with mucosal biopsy. RESULTS: Esophageal mucosa biopsy specimens were quickly and safely obtained during endoscopic evaluation. There were no complications. Reflux esophagitis was present in 54% of biopsy specimens, as suggested by basal cell hyperplasia, papillary elongation, and/or inflammatory cell infiltrates. CONCLUSION: Gastroesophageal reflux is often difficult to diagnose in the pediatric population. When direct laryngoscopy and bronchoscopy is performed during examination of the child with airway symptoms, the addition of esophagoscopy with mucosal biopsies will safely and quickly provide data regarding the potential contribution of gastroesophageal reflux.

Biopsy↗

IgG antibody levels in the sinus, ear, and airway in a rabbit model of sinusitis with Bacteroides.

OBJECTIVE: To evaluate distribution of IgG antibodies (Ab) in the airway, ear, and sinuses in association with inflammatory changes in a rabbit sinusitis model. DESIGN: We measured IgG Ab and lactate dehydrogenase levels in solutions from sinus, airway, and middle ear lavage and in serum, and determined interferon y messenger RNA expression in sinus and ear mucosa at 1, 2, 3, and 4 weeks after inoculation with Bacteroides fragilis. SUBJECTS: Six rabbits at each time point; controls were untreated (n=5) and sham-operated rabbits at 2 and 4 weeks (n=4-5). INTERVENTION: Bacteroides fragilis was inoculated into the left maxillary sinus with ostium closed. RESULTS: IgG Ab was undetectable in all controls. IgG Ab (>50 microg/g protein) was present at 2, 3, and 4 weeks in most bilateral sinus lavage samples and in 2 of 6, 5 of 6, and 6 of 10 ear lavage samples at 2, 3, and 4 weeks, respectively, following inoculation. Inflammatory changes (histological and lactate dehydrogenase) were much greater in the inflamed sinus. IgG Ab (>50 microg/g protein) was also detected in most bronchoalveolar lavage samples after 2 weeks. Interferon gamma mRNA was undetectable in all untreated and most sham-operated controls but was detected in the bilateral sinus mucosa at 1 to 2 weeks, and remained detectable up to 4 weeks in most rabbits. Serum IgG Ab levels positively correlated with those in lavage samples, with highest correlation with right sinus lavage IgG Ab levels (r=0.56, P<.001). CONCLUSION: IgG Ab levels in the upper airway mucosa likely increase within 2 weeks following bacterial inoculation as a part of mucosal immune responses independent of tissue necrosis.

Animals↗

Full polysomnographic evaluation of the infant airway.

BACKGROUND: There is little information regarding full polysomnographic examination of infants for the evaluation of stridor or stertor. OBJECTIVE: To determine the usefulness of polysomnographic examination in the evaluation of airway disorders in infants. DESIGN: Case review series. SETTING: Tertiary pediatric care center and sleep disorders center. PATIENTS: Younger than 10 months. INTERVENTION: Full polysomnography and treatment with a positive-pressure assistive device or surgery if indicated. MAIN OUTCOME MEASURES: Electroencephalographic findings, amount and length of apnea, percentage of desaturation and carbon dioxide retention, sleep architecture, amount of hypopnea as well as sleep arousals, episodes of gastroesophageal reflux, and clinical follow-up. RESULTS: Of 60 full pediatric polysomnograms performed at our institution each year, only 17 were obtained in children younger than 10 months for determination of symptoms of stridor or stertor over the past 8 years. In several cases, interpretation of 4-channel studies led to the wrong conclusions and inadequate treatment. Diagnoses made using full polysomnography included 3 children with seizure disorders, 1 with disorganized brain activity, 2 with gastroesophageal reflux, and 7 with anatomical obstructions, 3 of whom were successfully treated with a positive-pressure assistive device and 4 of whom were treated surgically. CONCLUSIONS: Full polysomnography provides physiological data that complement anatomical data obtained via endoscopy and is a useful tool for evaluating the significance of airway disorders in infants.

Bronchoscopy↗

Endoscopic management of pediatric posterior glottic stenosis.

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.

Arytenoid Cartilage↗

Magnetic resonance imaging of the pediatric airway.

OBJECTIVE: To determine the role of magnetic resonance imaging (MRI) and how it relates to endoscopy as well as to other imaging modalities in the evaluation of pediatric airway disorders. DESIGN: A review study of children with various distal airway disorders over a 3-year period. Surgical procedures as well as all diagnostic imaging modalities were reviewed and analyzed with respect to clinical outcome. SETTING: Academic tertiary care children's hospitals. PATIENTS: Forty-nine children between the ages of 1 week and 14 years with the signs and symptoms of distal airway disorders. INTERVENTIONS: Forty-five of 49 children underwent airway endoscopy. Fourteen children also underwent fluoroscopy and 4 underwent echocardiography. When indicated, open surgical repair was performed and used to verify findings in 32 cases. RESULTS: Magnetic resonance imaging was the most accurate modality in defining extrinsic airway abnormalities. The findings of echocardiography were incorrect in 2 of 4 cases, and fluoroscopy, although accurate for tracheal narrowing and tracheomalacia, often could not elucidate that exact cause or missed left mainstem bronchial compression. Furthermore, tracheal narrowing to 50% or greater on MRI correlated 100% with the need for surgical intervention. CONCLUSIONS: Magnetic resonance imaging is a useful modality that has allowed us to accurately diagnose extrinsic pediatric tracheal abnormalities. In certain cases, MRI scans can be obtained prior to endoscopy. In those cases, definitive endoscopy and open repair are performed at the same procedure instead of at 2 separate procedures (ie, one for diagnostic endoscopy and the other for definitive repair).

Adolescent↗