Impact on hearing of routine ear suctioning at the tympanic membrane.

OBJECTIVE: Patient and equipment safety has become increasingly scrutinized in today's medical care. Routine otolaryngologic evaluation often involves suctioning with Frazier-type suction devices in the ear canal for improved visualization, but data are limited on the potential acoustic trauma from ear canal suction devices. This study intends to document the objective and subjective effects of ear canal suctioning to identify any risk for hearing threshold shifts or other potential negative effects. PATIENTS AND METHODS: Prospective study on 21 healthy volunteers enlisted for evaluation. Presuctioning tympanogram, audiogram, and otoacoustic emissions data were obtained. Spectrum analyses were recorded during ear canal suctioning with a probe microphone placed lateral to the tympanic membrane. Subjective data were recorded, and a follow-up audiogram and otoacoustic emissions were obtained to identify any temporary threshold shifts. RESULTS: Spectrum analyses revealed a high degree of variability between subjects. A peak intensity of 111 dB sound pressure level was recorded. All patients tolerated suctioning, and none reported hearing loss. No threshold shifts were observed. Subjective data failed to correlate with the objective recorded intensities. CONCLUSIONS: Clinicians and patients need to be acutely aware of potential risks and benefits from any medical intervention. Routine ear canal suctioning can be extremely loud and uncomfortable for patients. This study failed to document objective proof of hearing detriment from ear canal suctioning, although the possibility exists during office and surgical intervention. Further study and potential alternative suctioning methods deserve attention.

Interferon regulatory factor-1 down-regulates cytokine-induced IP-10 expression in pancreatic islets.

BACKGROUND: Interferon (IFN)-gamma acts synergistically with interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha to activate isoform of nitric oxide synthetase (iNOS) gene expression, induce apoptosis, and impair glucose-stimulated insulin release (GSIR) in pancreatic islets. This effect is an important mechanism of islet dysfunction in models of pancreatitis, type I diabetes, and islet allograft rejection. We tested the hypothesis that transcription factor interferon regulatory factor (IRF)-1 plays a regulatory role in both this cytokine-induced islet injury and cytokine-induced gene expression for chemotactic chemokines. METHODS: Isolated islets from wild-type (WT) or IRF-1(-/-) C57BL/6 mice were cultured in a mixture of IL-1beta, TNF-alpha, and IFN-gamma +/- the iNOS inhibitor L-NMMA. The following end points were assessed: i) GSIR; ii) rates of apoptosis; and iii) gene expression for iNOS, IRF-1 and inducible protein (IP)-10, monocyte chemoattractive protein (MCP)-1, macrophage inflammatory protein-1alpha, and macrophage inflammatory protein-1beta. RESULTS: Cytokine-treated WT islets demonstrated an increase in IRF-1 and iNOS gene expression, inhibition of GSIR, increased rates of apoptosis, and increased gene transcription and protein release for IP-10 and MCP-1. Cytokine-treated IRF-1(-/-) islets demonstrated relatively less iNOS gene expression, preserved GSIR, reduced rates of apoptosis, and a more marked increase in transcription for IP-10 and MCP-1 and in IP-10 protein release. L-NMMA-cotreated WT islets were completely resistant to cytokine-induced dysfunction and apoptosis but demonstrated the same degree of cytokine-induced chemokine gene expression as cytokine-treated WT without L-NMMA. CONCLUSIONS: IFN-gamma, IL-1beta, and TNF-alpha in combination induce chemokine gene expression in pancreatic islets. Transcription factor IRF-1 mediates cytokine-induced islet dysfunction, apoptosis, and iNOS gene expression but down-regulates IP-10 gene expression.

Genetic deletion of chemokine receptor CXCR3 or antibody blockade of its ligand IP-10 modulates posttransplantation graft-site lymphocytic infiltrates and prolongs functional graft survival in pancreatic islet allograft recipients.

BACKGROUND: Interaction of chemokine receptor CXCR3 with its ligand IP-10 mediates effector cell trafficking to sites of allograft rejection in murine models of whole organ allotransplantation. We hypothesized that blocking the CXCR3/IP-10 interaction would impair posttransplantation leukocyte trafficking to and delay rejection of pancreatic islet allografts. METHODS: A/J strain murine islets were implanted to the kidney capsule of H-2 disparate, streptozotocin-induced diabetic wild type (WT), CXCR3 deficient (CXCR3(-/-)) or IP-10 antibody-treated WT (alphaIP-10) C57BL/6 recipients. Representative grafts from each group were harvested at day 7. Ribonuclease protection assay was used to determine gene expression for cell markers F4/80 (macrophages), CD8 (type I T cells), CD4 (type II T cells), and CD 19 (natural killer cells), and for chemokines IP-10, MIP-1alpha, MIP-1beta, MCP-1, and RANTES. Immunohistochemistry was used to confirm ribonuclease protection assay infiltrate data. Graft-site chemokine gene expression and cellular infiltrate were correlated with time to functional graft rejection. RESULTS: Untreated WT recipients demonstrated heavy graft-site cell infiltrates and increased graft-site gene expression for cell markers F4/80, CD8, CD4, and CD19, and for chemokines RANTES, IP-10, and MIP-1beta at day 7. In comparison with untreated WT, alphaIP-10-treated WT and CXCR3(-/-) recipients demonstrated the same degree of chemokine gene expression but less lymphocytic infiltrate. The mean length of allograft survival was 12.7 +/- 3.1 days in untreated WT versus 20.2 +/- 2.7 days (P <.05) for CXCR3(-/-)- and 19.7 +/- 2.3 days (P <.05) for alphaIP-10-treated WT recipients. CONCLUSIONS: CXCR3 gene deletion or alphaIP-10 antibody therapy modulates posttransplantation lymphocytic graft infiltration and statistically prolongs graft survival in murine islet allograft recipients.

The relationship of tinnitus, hyperacusis, and hearing loss.

The triad of tinnitus, hyperacusis, and hearing loss remains an often-underdiagnosed combination of symptoms that causes physical, mental, and emotional distress for millions of patients. To the best of our knowledge, no review has heretofore been published in the literature regarding the possible relationship among these three entities. We believe that these symptoms may have a common pathophysiology. Specifically, improper function of cochlear hair cells may result in a hearing loss secondary to the failure of these cells to propagate proper signals through the auditory centers. In response to an incongruous neural message, higher auditory cortical centers may adapt and remodel transmitted sound. This neuroplasticity may lead to an increased perception of volume in the auditory cortex (hyperacusis) and to the perception of phantom sounds (tinnitus). Awareness of the potential relationship among tinnitus, hyperacusis, and hearing loss may contribute to improved diagnosis, treatment, and follow-up for patients with these conditions.

Extraorbital pseudotumor of the petrous apex: biopsy via a transnasal endoscopic approach.

Extraorbital idiopathic pseudotumors of the skull base are very uncommon. We report the case of a 50-year-old woman who presented with left ophthalmoplegia and vision loss. Imaging studies revealed an enhancing lesion involving the left petrous apex and cavernous sinus. A transnasal endoscopic approach was used to obtain a biopsy of the left petrous apex. Pathology identified the lesion as an idiopathic pseudotumor. The patient was treated with high-dose steroids and steroid-sparing immunomodulators, and she experienced a significant improvement. To the best of our knowledge, this is the first reported case of a transnasal endoscopic approach to a biopsy of a pseudotumor involving the petrous apex. We discuss the features of this case, and we review the literature on this condition.

Temperature variations of nasal endoscopes.

OBJECTIVES: Advances in light sources and endoscopes have improved illumination during endoscopic sinus surgery. However, these advances have also increased the temperatures the equipment reaches during the course of procedures. Limited data exist on temperature variations of nasal endoscopes and the potential risks of burns to drapes and patients. We attempt to quantify temperature variations of nasal endoscopes and light cords. METHODS: Various endoscopes, light cords, and xenon light sources were used to measure temperature increases over time. Temperatures were measured with noncontact thermometers using different combinations of endoscopes, light cords, and light sources at multiple intervals up to 30 minutes over 30 trials. Variables assessed included endoscope age, light cord age, light source type, and light source age. Also, extended time trials were repeated up to 180 minutes. RESULTS: Endoscope tip temperatures peaked at 62.5°C. Additional studies performed with the cord and light source alone reached a maximum temperature of nearly 200°C. The ages of light cords and scopes do lead to statistically significant changes in heat production. Higher wattage light sources may increase potential temperatures. CONCLUSIONS: Patient safety is a preeminent concern for all procedures. Although the endoscope temperatures appear low risk for patient injury, the light cord itself creates extreme temperatures. It is important to monitor the endoscope and light cords for extreme temperatures to avoid patient injury.

Papillary carcinoma arising in median ectopic thyroid tissue: management of the thyroid gland.

Thyroid tissue in an ectopic location is rare, 1 in 100,000 to 300,000 persons, and usually in the lateral neck. Median ectopic thyroid tissue is even more unusual, with the vast majority of cases being lingual thyroid tissue. We present a case of carcinoma arising in median, nonlingual ectopic thyroid tissue along with an analysis of the literature to determine the most appropriate management of the orthotopic thyroid gland.

CCK-A receptor induction and P38 and NF-kappaB activation in acute pancreatitis.

Bile-pancreatic duct ligation in rats excludes bile-pancreatic juice from the gut and induces acute pancreatitis. Bile-pancreatic juice exclusion from the gut results in increased plasma cholecystokinin (CCK) levels. CCK-A receptor-mediated exocrine pancreatic hyperstimulation is implicated in disease pathogenesis. In the present study, we show for the first time a progressive rise in CCK-A receptor protein expression in ligation-induced acute pancreatitis in rats. As CCK-A receptor induction could amplify CCK-mediated acinar hyperstimulation and exacerbate acinar cell stress with activation of the p38(MAPK) stress kinase pathway, we studied CCK-A receptor protein expression and p38(MAPK) activation in duct ligation-induced acute pancreatitis in rats. Compared to sham-operated controls, acute pancreatitis induced by bile-pancreatic duct ligation associates with a temporal increase in pancreatic CCK-A receptor protein expression, p38(MAPK) expression and activation, and NF-kappaB activation. These findings may have significance in the mechanism of disease pathogenesis in this experimental model.

Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder.

Panic disorder (PD) is a clinical syndrome characterized by recurrent discrete episodes of fear accompanied by a variety of physiological and psychological symptoms, often with prominent respiratory components. A series of clinical observations has led some investigators to hypothesize that subtle alterations in ventilatory regulation are integral to at least a subtype of PD. In order to identify genetic factors that might predispose individuals to these alterations in ventilatory response, we conducted single stranded conformation polymorphism analysis across the exons of the lactate dehydrogenase A and B genes (LDHA and LDHB) using DNA prepared from 86 subjects previously characterized by respiratory response to a CO(2) challenge with a variable genetic loading for PD. Remarkably, a single conserved LDHA exon 5 haplotype conferred increased risk for a paradoxical ventilatory response pattern to CO(2) inhalation which robustly separated well subjects at high risk for PD from low-risk control subjects. But, comparison of LDHA exon 5 genotypes in PD probands (n = 25) to that of random newborn controls (n = 182) did not demonstrate any significant differences. Given the pivotal role of LDH in the metabolism of lactate, a known inducer of panic attacks, and the dependence of LDH activity on cell pH, we suggest that LDHA polymorphisms may contribute to the variability to CO(2) respiratory challenge.

Role of elastin polymorphisms in panic disorder.

Panic disorder (PD) is a complex neuropsychiatric disorder that has been associated with an increased frequency of mitral valve prolapse. Elastin is a prominent component of mitral valves and, in a genome screen of 23 pedigrees with PD, we found evidence of linkage to the region of chromosome 7 that contains the elastin gene (ELN). Therefore, we examined the minimal essential promoter and coding regions of ELN in 23 independent probands from the families in our linkage studies using single strand conformational polymorphism analysis. We found three polymorphisms including one that coded for a non-conservative amino acid change. However, none of these polymorphisms were associated with panic disorder in a case-control analysis or linked to it in multiplex pedigrees. In our pedigrees, exonic polymorphisms in ELN do not play a major role in the genetic vulnerability to PD.