Avoiding airway obstruction after pediatric adenotonsillectomy

International Journal of Pediatric Otorhinolaryngology
Volume 73, Issue 6, June 2009, Pages 803-806
Glenn Isaacsona,  aDepartment of Otolaryngology – Head & Neck Surgery, Temple University School of Medicine, USA  bDepartment of Pediatrics, Temple University School of Medicine, USA

Abstract
Objective

To evaluate the efficacy of a protocol designed to prevent post-adenotonsillectomy airway obstruction in small children with obstructive sleep apnea.
Design

Computerized retrospective review of single surgeon case series.
Setting

Tertiary children's medical center.
Methods

Children with sleep study proven obstructive sleep apnea or children under the age of 3 years with clinically suspected obstructive sleep apnea were treated according to a protocol that included: (1) rapid bloodless tonsillectomy; (2) repeated release of the tonsillar retractor; (3) avoidance of uvular edema; (4) routine intra-operative intranasal oxymetazoline, and placement of nasal airway; (5) extended recovery room observation. Primary outcome measures were (1) avoidance of unexpected intensive care unit admission; (2) post-extubation pulmonary edema; (3) aspiration pneumonia.
Results

During the period March 2004–August 2007, 864 children underwent adenotonsillectomy by a single surgeon—604 for the indication of obstructive sleep apnea or adenotonsillar hypertrophy with obstruction. Two hundred and ten were under the age of 3 years or had sleep study proven obstructive sleep apnea. There were two unexpected admissions to the pediatric intensive care unit for persistent upper airway obstruction—none required intubation. No child developed post-obstructive pulmonary edema. Three children were treated for infiltrates consistent with aspiration pneumonitis.
Conclusion

Most cases of post-extubation pulmonary edema and pneumonia can be avoided in young children and those with mild-to-moderate obstructive sleep apnea following a protocol that anticipates and avoids precipitating causes of upper airway obstruction.

Ciprofloxacin 0.3%/Dexamethasone 0.1% Sterile Otic Suspension for the Topical Treatment of Ear Infections: A Review of the Literature

The Pediatric Infectious Disease Journal:
February 2009 - Volume 28 - Issue 2 - pp 141-144
Wall, G Michael PhD; Stroman, David W. PhD; Roland, Peter S. MD; Dohar, Joseph MD

Wall, G Michael PhD; Stroman, David W. PhD; Roland, Peter S. MD; Dohar, Joseph MD

Abstract

The objective of this article is to review the literature related to ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension. A systematic literature search utilizing Medline was conducted to identify peer-reviewed articles related to safety and efficacy. A total of 47 publications were identified and reviewed herein. The literature supports the use of antibiotic/antiiflammatory combination ear drops in the treatment of both acute otitis externa and acute otitis media in pediatric patients with tympanostomy tubes.

Ciprofloxacin/dexamethasone has been demonstrated as safe and effective with regard to clinical cures and microbiological eradication of pathogens in either disease with low treatment failure rates. Additionally, the literature also provides clear evidence for the contribution of dexamethasone when added to ciprofloxacin for the topical treatment of ear infections.

Analysis of 60 patients after tympanotomy and sealing of the round window membrane after acute unilateral sensorineural hearing loss.

Am J Otolaryngol. 2009 May-Jun;30(3):157-61. Epub 2008 Sep 21.
Gedlicka C, Formanek M, Ehrenberger K.

Department of Otorhinolaryngology, Head and Neck Surgery, University of Vienna, Vienna, Austria. claudia.gedlicka@meduniwien.ac.at

OBJECTIVE: This retrospective study was performed to evaluate the effectiveness of tympanotomy and sealing of the round window membrane after unilateral acute hearing loss.

DESIGN: All patients presenting idiopathic sudden hearing loss, acoustic, or barotrauma were treated with prednisolone and caroverine. Thirty-six patients had a mean pure tone hearing level worse than 70 dB. Recovery was defined as improvement of hearing threshold for 5 frequencies (250, 500, 1000, 2000, and 4000 Hz). If hearing did not improve after conservative treatment, an exploratory tympanotomy and sealing of the round window membrane were suggested. In the last 8 years, 60 patients with idiopathic sudden hearing loss, acoustic, or barotrauma underwent tympanotomy.

RESULTS: In 40 patients, we observed improvement of hearing level up to complete remission. In 20 patients, no change could be detected. In the group of patients with documented barotrauma, 12 patients showed improved hearing levels. Of 37 patients with idiopathic sudden hearing loss, 26 had an improved hearing after surgery. Most patients were operated on within 14 days (range, 1-60 days), but time of surgery had no influence on outcome in patients with idiopathic hearing loss. In contrast, in patients with barotrauma, time of surgery seems to have an influence on outcome.

CONCLUSIONS: Tympanotomy and sealing of the round window membrane can be recommended in cases of acute hearing loss after failure of conservative treatment.

An unusual case of cotton wool use to improve hearing.

J Laryngol Otol. 2009 Dec 23:1-3. [Epub ahead of print]
Bergin M, Murray D, Bird P.

*Department of Otolaryngology Head and Neck Surgery, Christchurch Hospital, New Zealand.

Objectives: To report an unusual observation whereby hearing was improved by insertion of cotton wool onto a retracted tympanic membrane, and to explore potential explanations for this.

Case report:We report the case of a 56-year-old woman with a severe mixed hearing loss who was noted to have a significant improvement in her hearing using a technique shown to her many years ago by a Russian physician. Upon application of a moist piece of cotton wool, gains of up to 40 dB were observed. This was associated with a significant subjective improvement in hearing. We discuss potential mechanisms for this effect, including amplification, a baffle effect and phase differences.

Conclusion:The mechanism of the hearing improvement observed in this case is unknown, but is likely to be related to sound amplification from the relatively large surface area of the cotton wool to the smaller oval window.

Diagnostic Value of Nasal Allergen Challenge Combined With Radiography and Ultrasonography in Chronic Maxillary Sinus Disease

Arch Otolaryngol Head Neck Surg. 2009;135(12):1246-1255.Zdenek Pelikan, MD, PhD

Objective To investigate the possible role of nasal allergy in chronic disease of the maxillary sinuses (CDMS) by means of nasal provocation test (NPT) with allergen combined with radiography and ultrasonography.

Design Prospective clinical controlled study.

Setting Academic referral center.

Patients Seventy-one patients with CDMS and 16 control subjects with allergic rhinitis but no history of sinus disease.

Interventions In the 71 patients, a total of 135 NPTs and 71 control challenges with phosphate-buffered saline were performed by rhinomanometry combined with radiography and ultrasonography. In the control patients, 16 positive NPTs were repeated and combined with radiography and ultrasonography.

Main Outcome Measures Number, type, and timing of nasal responses with accompanying changes on radiographs and ultrasonograms.

Results Of the 71 patients, 67 developed 104 positive nasal responses of various types (P < .001), 89 of which were accompanied by significant changes on radiographs (P = .008), whereas 83 were also associated with significant changes on ultrasonograms (P = .007). No significant changes on the radiographs or the ultrasonograms were recorded during the 71 phosphate-buffered saline control tests in the patients with CDMS (P = .14 and .06, respectively) or during the 16 NPTs in control subjects (P = .15 and .12, respectively). The radiographic and ultrasonographic findings were significantly correlated (r = 0.81; P < .01).

Conclusions Nasal allergy may be involved in some patients with CDMS, resulting in appearance of a maxillary sinus response. Monitoring this response by means of serial ultrasonography and, if necessary, also by conventional radiography or computed tomography simultaneously with the nasal challenge with allergen seems to be a very useful diagnostic supplement allowing additional therapeutic measures focused on the nasal allergy.

The Histologic Relationship of Preauricular Sinuses to Auricular Cartilage

Arch Otolaryngol Head Neck Surg. 2009;135(12):1262-1265.
Brian Dunham, MD; Martha Guttenberg, MD; Wynne Morrison, MD; Lawrence Tom, MD


Objective To determine the histologic relationship and distance between excised preauricular epithelial sinus tract and the adjacent auricular cartilage (sinocartilaginous distance) in a series of patients. The excision of preauricular sinuses is a common surgical procedure. Recurrences are frequent and can be technically challenging. While advocated by several authors, the surgical removal of adjacent auricular cartilage is not universally performed.

Design Retrospective case series.

Setting Children's Hospital of Philadelphia.

Patients Fifty-two pediatric patients who underwent surgical excision of preauricular sinus tracts and adjacent auricular cartilage.

Interventions Between September 1, 2005, and July 31, 2007, the preauricular sinus tracts and adjacent auricular cartilage were excised from 52 pediatric patients. A pathologist reviewed a total of 58 specimens to determine the relationship between epithelial tract and cartilage.

Main Outcome Measure The sinocartilaginous distance in microns.

Results Patient ages ranged from 8 months to 17 years (mean age, 4 years). In all but 1 case, the tracts were in close proximity to the cartilage. The average sinocartilaginous distance was 472 µm (median distance, 400 µm); the 25th percentile was 250 µm. In over 50% of the specimens, the sinocartilaginous distance was less than 0.5 mm, and in nearly all of the these, the epithelial tract was in continuity with stromal tissue histologically indistinguishable from perichondrium.

Conclusions The observed sinocartilaginous distances suggest that it may be difficult to dissect most sinus tracts from the cartilage. The routine removal of a small portion of auricular cartilage along with the sinus tract may yield a more thorough excision and help to prevent recurrence.

Location of Bacterial Biofilm in the Mucus Overlying the Adenoid by Light Microscopy Birgit Winther, MD; Brian C. Gross, MD; J. Owen Hendley, MD; Stephen V. Early, MD Arch Otolaryngol Head Neck Surg. 2009;135(12):1239-1245. Objective To determine the location of bacteria and biofilm in adenoid tissue and in mucus overlying the adenoid. Design Adenoids removed in 1 piece were oriented to the cephalic and caudal ends. Mucus was fixed by the gradual addition of Carnoy fluid. Consecutive histologic sections were stained with periodic acid–Schiff for visualization of the exopolysaccharide matrix, Giemsa for visualization of bacteria and cells, and fluorescent in situ hybridization with a universal probe for visualization of bacteria. Setting Department of Otolaryngology–Head and Neck Surgery, University of Virginia. Participants We obtained adenoids from children 10 years or younger who had chronic adenotonsillitis or obstructive sleep apnea. Twenty-seven adenoids were used to develop the fixation method. We examined histologic sections from 9 of 10 adenoids fixed using the final fixation protocol. One adenoid that was missing the surface epithelium was excluded from further evaluation. Main Outcome Measure Identification of bacteria by light microscopy. Results Bacteria in large numbers were present in the mucus overlying the surface of all 9 adenoids; bacteria were not found in the parenchyma of the adenoids below the epithelial surface. Bacterial biofilms were present on 8 of the 9 adenoids. Sessile (attached) biofilm was present on the caudal end of only 1 adenoid. Multiple planktonic (unattached) biofilms were present on 7 adenoids, always in areas not subject to mucus flow. Biofilms were most common on the caudal portions of adenoids. Conclusions Bacteria of the adenoid reside in secretions on the surface and in crypts. Biofilms, predominantly planktonic, were present on 8 of 9 adenoids excised because of hypertrophy. Whether biofilms have a role in the causation of adenoid hypertrophy is not known.

Arch Otolaryngol Head Neck Surg. 2009;135(12):1239-1245.
Birgit Winther, MD; Brian C. Gross, MD; J. Owen Hendley, MD; Stephen V. Early, MD 

Objective To determine the location of bacteria and biofilm in adenoid tissue and in mucus overlying the adenoid.

Design Adenoids removed in 1 piece were oriented to the cephalic and caudal ends. Mucus was fixed by the gradual addition of Carnoy fluid. Consecutive histologic sections were stained with periodic acid–Schiff for visualization of the exopolysaccharide matrix, Giemsa for visualization of bacteria and cells, and fluorescent in situ hybridization with a universal probe for visualization of bacteria.

Setting Department of Otolaryngology–Head and Neck Surgery, University of Virginia.

Participants We obtained adenoids from children 10 years or younger who had chronic adenotonsillitis or obstructive sleep apnea. Twenty-seven adenoids were used to develop the fixation method. We examined histologic sections from 9 of 10 adenoids fixed using the final fixation protocol. One adenoid that was missing the surface epithelium was excluded from further evaluation.

Main Outcome Measure Identification of bacteria by light microscopy.

Results Bacteria in large numbers were present in the mucus overlying the surface of all 9 adenoids; bacteria were not found in the parenchyma of the adenoids below the epithelial surface. Bacterial biofilms were present on 8 of the 9 adenoids. Sessile (attached) biofilm was present on the caudal end of only 1 adenoid. Multiple planktonic (unattached) biofilms were present on 7 adenoids, always in areas not subject to mucus flow. Biofilms were most common on the caudal portions of adenoids.

Conclusions Bacteria of the adenoid reside in secretions on the surface and in crypts. Biofilms, predominantly planktonic, were present on 8 of 9 adenoids excised because of hypertrophy. Whether biofilms have a role in the causation of adenoid hypertrophy is not known.

The role of neurotrophins in the pathophysiology of allergic rhinitis

Current Opinion in Allergy and Clinical Immunology (Nov 2009) 
 Raap U, Braunstahl GJ

PURPOSE OF REVIEW: Allergic rhinitis is characterized by allergic airway inflammation and a hyperresponsiveness to nonspecific stimuli which is partly neuronally controlled. In this regard, neurotrophins are prime candidates as mediators of neuronal and immunological plasticity and they will be the focus of the current review.
RECENT FINDINGS: Neurotrophins including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are expressed in the nasal mucosa. The majority of NGF expression has been found in eosinophil granulocytes, the glandular apparatus and peripheral nerves. As shown recently, nasal allergen provocation upregulates BDNF expression in nasal mucosa and NGF expression on peripheral nerves and nasal lavage in patients with allergic rhinitis. In this regard, increased BDNF expression positively correlates with the maximum increase in total nasal symptom score. The neurotrophin receptors including pan-neurotrophin receptor p75, tyrosine kinase A (trkA) and trkB are expressed in nasal tissue. TrkA is expressed on endothelial, p75 on peripheral nerves and trkB on nasal mucosa mast cells that decreases after allergen provocation. The expression of these neurotrophin receptors is increased on peripheral blood eosinophils in allergic rhinitis compared with nonatopic controls. Further, BDNF and NGF exert immunomodulatory functions on eosinophils of patients with allergic rhinitis. Finally, eosinophils of patients with allergic rhinitis are capable of BDNF and NGF production.
SUMMARY: Neurotrophins represent prime candidates in upper airway pathophysiology in allergic rhinitis. Research on neurotrophins in allergic rhinitis is thus becoming a progressively more exciting field and may reveal new and promising therapeutic options for the future.

Recent advances in otitis media

 Pediatric Infectious Disease Journal 28 (10 Suppl), S133-7 (Oct 2009)
 Pelton SI, Leibovitz E
Otitis media (OM) is a pervasive illness in infants and children, and many children suffer multiple episodes during the first years of life. High rates of acute otitis media (AOM) are reported in developed and emerging countries. Early onset is common in both settings. Recurrent OM is associated with several factors, including early onset of disease, having a sibling with a history of AOM and absence of breast-feeding. Early onset disease has been hypothesized to result from Eustachian tube dysfunction, immunologic naivete and immaturity, and viral upper respiratory tract infection. Nasopharyngeal colonization with bacterial otopathogens increases the likelihood of AOM and the disease is most frequent in children with viral respiratory tract infection colonized with multiple otopathogens (Streptococcus pneumoniae, nontypeable Haemophilus influenzae [NTHi], Moraxella catarrhalis), potentially as a result of inflammation resulting from competition among the bacterial species within the nasopharynx. Epidemiologic observations and studies of pathogenesis suggest that successful strategies for reducing the burden of disease will be best accomplished by targeting multiple viral and/or bacterial pathogens and preventing early onset disease. Guidelines (2004) for the treatment of AOM in children establish a clear hierarchy among the various antibacterials for the treatment of this disease. Failure to achieve early bacterial eradication during antibiotic therapy for AOM increases the clinical failure rates in AOM in young children. Most recurrent AOM episodes occurring within 1 month after successful completion of antibiotic therapy are due to new otopathogens. Failure to eradicate middle ear and/or nasopharyngeal pathogens is associated with higher rates of clinical recurrent AOM, even when the patients show clinical improvement or cure at the end of therapy for the initial episode. Optimal strategy for the prevention of AOM recurrences requires sterilization of the middle ear and eradication of nasopharyngeal carriage of otopathogens during antimicrobial therapy.

The role of dyslipidemia in sensorineural hearing loss in children

Int J Pediatr Otorhinolaryngol. 2009 Nov 23. [Epub ahead of print]

Anbari S, Isazadeh D, Safavi A, Alaie M, Azizi F.

Department of Otorhinolaryngology, Taleghani Hospital, Shahid Beheshti University, M.C., Parvaneh St., Yaman St., Velenjak, Tehran, Iran.

OBJECTIVE: The relationship between dyslipidemia and hearing is controversial; especially in children, the available evidences are scarce. This study is designed to determine whether dyslipidemia is associated with sensorineural hearing loss in a group of 5-18-year-old children and adolescents.

METHODS: Through an analytic cross-sectional study, records of all 5-18-year-old children who attended the pediatric endocrinology clinic of Loghman Hospital in Tehran, Iran, between April 2007 and April 2009 were reviewed. Records with a lipid profile were determined. Lipid profiles were repeated for eligible cases; they were enrolled if the results were the same as before (normal or dyslipidemic). Hearing loss, speech discrimination scores and lipid profiles were analyzed.

RESULTS: When controlled for age and sex, no association between dyslipidemia and sensorineural hearing loss were found. There was also no statistically significant relationship between dyslipidemia and sensorineural hearing loss in different age groups.

CONCLUSIONS: Dyslipidemia seems to have no association with sensorineural hearing loss in 5-18 years old children according to this study.

PMID: 19939472 [PubMed - as supplied by publisher]

Vestibular autonomic regulation (including motion sickness and the mechanism of vomiting).

Curr Opin Neurol. 1999 Feb;12(1):29-33.

Balaban CD.

Collaborators (1)

University of Pittsburgh, Department of Otolaryngology, PA 15213, USA. cbalaban@vms.cis.pitt.edu

Autonomic manifestations of vestibular dysfunction and motion sickness are well established in the clinical literature. Recent studies of 'vestibular autonomic regulation' have focused predominantly on autonomic responses to stimulation of the vestibular sense organs in the inner ear. These studies have shown that autonomic responses to vestibular stimulation are regionally selective and have defined a 'vestibulosympathetic reflex' in animal experiments.

Outside the realm of experimental preparations, however, the importance of vestibular inputs in autonomic regulation is unclear because controls for secondary factors, such as affective/emotional responses and cardiovascular responses elicited by muscle contraction and regional blood pooling, have been inadequate. Anatomic and physiologic evidence of an extensive convergence of vestibular and autonomic information in the brainstem suggests though that there may be an integrated representation of gravitoinertial acceleration from vestibular, somatic, and visceral receptors for somatic and visceral motor control. In the case of vestibular dysfunction or motion sickness, the unpleasant visceral manifestations (e.g. epigastric discomfort, nausea or vomiting) may contribute to conditioned situational avoidance and the development of agoraphobia.

PMID: 10097881 [PubMed - indexed for MEDLINE]

Neuroanatomic substrates for vestibulo-autonomic interactions.

J Vestib Res. 1998 Jan-Feb;8(1):7-16.

Balaban CD, Porter JD.

Department of Otolaryngology, University of Pittsburgh School of Medicine, USA.

Recent anatomical studies have identified a network of central neural circuits that appear to integrate vestibular and autonomic information. Like vestibulo-ocular and vestibulospinal circuits, these pathways appear to be under inhibitory modulation by distinct regions in the medial aspect of the cerebellar cortex. These central circuits have the potential to explain the known influence of vestibular stimulation on autonomic motor responses through descending effects on brain stem autonomic regions. In a more global context, the extensive convergence of vestibular and autonomic information in both vestibular and autonomic brain regions is consistent with the concept that vestibular and visceral information (for example, blood pooling and visceral proprioception) are used to form a central representation of gravitoinertial parameters during movements. This representation can influence neural circuitry involved in postural control, cardiovascular control, perception of the spatial vertical and emotional or affective responses.

PMID: 9416584 [PubMed - indexed for MEDLINE]

What Are Cluster Headaches? What Causes Cluster Headaches?

What Are Cluster Headaches? What Causes Cluster Headaches?

How to improve the accuracy of diagnosing otitis media with effusion in a pediatric population

International Journal of Pediatric Otorhinolaryngology

Dong-Hee Lee

Department of Otolaryngology-Head and Neck Surgery, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, College of Medicine, #65-1 Geumo-Dong, Uijeongbu City, Gyeonggi-Do, Seoul 480-717, Republic of Korea

Received 11 September 2009;  

revised 16 October 2009;  

accepted 23 October 2009.  

Available online 25 November 2009

Abstract

Objective

To determine the accuracy of pneumatic otoscopy, a tympanogram and otomicroscopy for diagnosing otitis media with effusion (OME) in a pediatric population.

Study design

Prospective blinded clinical and IRB-approved study at a secondary referral hospital.

Subjective and methods

Eighty-one children (155 ears) were recruited for this study, who were referred to my secondary referral hospital after OME was diagnosed at other primary clinics. The examiner was blinded for the findings of the diagnostic tools. Myringotomy under local anesthesia was used as the diagnostic reference standard. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the three diagnostic tools were calculated.

Results

Otomicroscopy was the most sensitive and specific tool among the three diagnostic tools. Otomicroscopy showed the best agreement with myringotomy (kappa = 0.784).

Conclusion

Otomicroscopy can make a more accurate diagnosis even for children who are seen at an outpatient clinic. The much higher specificity of otomicroscopy makes it the best confirmative test and its much higher positive predictive value can prevent a late diagnosis of OME, which can result in severe sequelae.

Mouse study sheds light on hearing loss in older adults

Mouse study sheds light on hearing loss in older adults

Infratemporal hydatid cyst: a case presenting with blindness

The Journal of Laryngology & Otology 

Cambridge University Press

Copyright © JLO (1984) Limited 2009

doi:10.1017/S0022215109991927

N Yazdania1 c1, A Basama1, M Heidaralia1, S Sharif Kashania1a2, M Hasibia3 and Z Mokhtaria1 a1 Otorhinolaryngology Research Centre, Amir-Alam Hospital, Tehran University of Medical Sciences, Iran a2 Department of Radiology, Amir-Alam Hospital, Tehran University of Medical Sciences, Iran a3 Department of Infectious Diseases, Amir-Alam Hospital, Tehran University of Medical Sciences, Iran

Abstract

Objective: We report a very rare case of a hydatid cyst in the infratemporal fossa, causing visual loss over a 10-day period, which disappeared with rapid surgical and medical treatment.

Case report: A 14-year-old girl presented with right exophthalmos and visual loss. Over a 10-day period, her visual acuity had decreased to detection of hand motion only, due to pressure on the optic nerve caused by a parapharyngeal cyst pressing through a inferior orbital fissure on the right side. A craniotomy had previously been performed for a right frontoparietal hydatid cyst. The patient had been treated intermittently with albendazole. The patient was primarily diagnosed with hydatid cyst, on the basis of her previous medical history and radiological findings, and underwent surgery. Three cysts were carefully removed from the right maxillary sinus, via a standard Caldwell–Luc approach, and the surgical area was irrigated with hypertonic saline.

Conclusion: Infratemporal hydatidosis is very rarely reported in the world literature, although hydatid cysts are endemic in many countries, including Iran. We discuss the common presenting features, investigation and treatment options for infratemporal hydatosis. Constant evaluation of adjacent organs is necessary, with treatment as required, due to the propensity of hydatidosis to recur in essential organs. Immediate surgery is recommended, both to prevent the development of disease and to improve the prognosis.

(Accepted July 23 2009)

Correspondence:
^c1 Address for correspondence: Dr S Sharif Kashani, Radiology Department, Amir-Alam Hospital, Tehran University of Medical Sciences, Sadi St, Enghelab Ave, Tehran, Iran Fax: 00982166704805 E-mail: Sh_Sh_md_rad@yahoo.com

Footnotes

Reflux esophagitis due to immune reaction, not acute acid burn

ScienceDaily (2009-11-19) -- Contrary to current thinking, a condition called gastroesophageal reflux disease might not develop as a direct result of acidic digestive juices burning the esophagus, researchers have found in an animal study.

Rather, gastroesophageal reflux spurs the esophageal cells to release chemicals called cytokines, which attract inflammatory cells to the esophagus. It is those inflammatory cells, drawn to the esophagus by cytokines, that cause the esophageal damage that is characteristic of GERD. The condition is manifested by symptoms such as heartburn and chest pain.


http://www.sciencedaily.com/releases/2009/11/091119111335.htm

Sounds can penetrate deep sleep and enhance associated memories upon waking

ScienceDaily (2009-11-20) -- They were in a deep sleep, yet sounds, such as a teakettle whistle, somehow penetrated their slumber. The 25 sounds were reminders of earlier spatial learning, though the research participants were unaware of the sounds as they slept. Yet, upon waking, memory tests showed that spatial memories had changed. Deep sleep, then, is actually is a key time for memory processing, the study suggests.


http://www.sciencedaily.com/releases/2009/11/091119193632.htm

Autonomic innervation of human airways: structure, function, and pathophysiology in asthma.

Neuroimmunomodulation. 1999 May-Jun;6(3):145-59.
van der Velden VH, Hulsmann AR.
Department of Immunology, Erasmus University and University Hospital Dijkzigt, Rotterdam, The Netherlands. vandevelden@immu.fgg.eur.nl

The human airways are innervated via efferent and afferent autonomic nerves, which regulate many aspects of airway function. It has been suggested that neural control of the airways may be abnormal in asthmatic patients, and that neurogenic mechanisms may contribute to the pathogenesis and pathophysiology of asthma.

In this review, the autonomic innervation of the human airways and possible abnormalities in asthma are discussed. The parasympathetic nervous system is the dominant neuronal pathway in the control of airway smooth muscle tone. Stimulation of cholinergic nerves causes bronchoconstriction, mucus secretion, and bronchial vasodilation. Although abnormalities of the cholinergic innervation have been suggested in asthma, thus far the evidence for cholinergic dysfunction in asthmatic subjects is not convincing.

Sympathetic nerves may control tracheobronchial blood vessels, but no innervation of human airway smooth muscle has been demonstrated. beta-Adrenergic receptors, however, are abundantly expressed on human airway smooth muscle and activation of these receptors causes bronchodilation. The physiological role of beta-adrenergic receptors is unclear and their function seems normal in asthmatic patients. Inhibitory nonadrenergic noncholinergic (NANC) nerves, containing vasoactive intestinal peptide and nitric oxide, may be the only neural bronchodilator pathways in human airways. Although a dysfunction of inhibitory NANC nerves has been proposed in asthma, thus far no differences in inhibitory NANC responses have been found between asthmatics and healthy subjects. Excitatory NANC nerves, extensively studied in animal airways, have also been detected in human airways.

In animal studies, stimulation of excitatory NANC nerves causes bronchoconstriction, mucus secretion, vascular hyperpermeability, cough, and vasodilation, a process called 'neurogenic inflammation'. Recent studies have demonstrated an interaction between the excitatory NANC nervous system and inflammatory cells. Neuropeptides may influence the recruitment, proliferation, and activation of leukocytes. On the other hand, inflammatory cells may modulate the neuronal phenotype and function. The functional relevance of the excitatory NANC nervous system and its interaction with the immune system in asthma still remains to be elucidated.

PMID: 10213912 [PubMed - indexed for MEDLINE]

Management of the trigeminocardiac reflex: facts and own experience.

Neurol India. 2009 Jul-Aug;57(4):375-80.
Arasho B, Sandu N, Spiriev T, Prabhakar H, Schaller B.
Department of Neurosurgery, University of Paris, France.

The trigeminocardiac reflex (TCR) is defined as the sudden onset of parasympathetic dysrhythmia, sympathetic hypotension, apnea, or gastric hyper-motility during stimulation of any of the sensory branches of the trigeminal nerve.
The proposed mechanism for the development of TCR is--the sensory nerve endings of the trigeminal nerve send neuronal signals via the Gasserian ganglion to the sensory nucleus of the trigeminal nerve, forming the afferent pathway of the reflex arc. It has been demonstrated that the TCR may occur with mechanical stimulation of all the branches of the trigeminal nerve anywhere along its course (central or peripheral). The reaction subsides with cessation of the stimulus. But, some patients may develop severe bradycardia, asystole, and arterial hypotension which require intervention. The risk factors already known to increase the incidence of TCR include: Hypercapnia; hypoxemia; light general anesthesia; age (more pronounced in children); the nature of the provoking stimulus (stimulus strength and duration); and drugs: Potent narcotic agents (sufentanil and alfentanil); beta-blockers; and calcium channel blockers. Because of the lack of full understanding of the TCR physiology, the current treatment options for patients with TCR include: (i) risk factor identification and modification; (ii) prophylactic measures; and (iii) administration of vagolytic agents or sympathomimetics.

PMID: 19770535 [PubMed - indexed for MEDLINE]

Cholinergic and neurogenic mechanisms in obstructive airways disease.

Am J Med. 1986 Nov 14;81(5A):93-102.
Bleecker ER.

Although primary neural control of airway function is through parasympathetic pathways, more recent evidence indicates that there are important adrenergic and non-adrenergic, non-cholinergic neural mechanisms that may also influence respiratory function. The parasympathetic nervous system component includes neural receptors in the airways as well as afferent and efferent pathways that travel in the vagus nerves. Afferent vagal sensory receptors mediate the response to irritant or rapidly adapting receptor activation, Hering-Breuer, and the unmyelinated "C" fibers or "J" receptor pathways. The motor component of the parasympathetic nervous system has several important functions that regulate tone in normal system has several important functions that regulate tone in normal and obstructed airways. These pathways affect the following respiratory structures: bronchial smooth muscle; the mucociliary system; the larynx; and the nose. Finally, the parasympathetic nervous system may play a role in some species in the control of breathing and in the hyperpneic responses associated with airflow obstruction. In addition to cholinergic neural mechanisms, bronchomotor tone may also be influenced by adrenergic mechanisms and non-adrenergic, non-cholinergic neural pathways. Although there is minimal innervation of the airways by the sympathetic nervous system, there is ample evidence that beta-adrenoreceptors are present on bronchial smooth muscle. Beta-receptor stimulation not only relaxes airway smooth muscle, but also inhibits mediator release from mast cells in the airways and may alter vascular permeability. Alpha-adrenoreceptors are found in human airways and stimulation of these receptors causes bronchoconstriction. Although the importance of alpha-adrenoreceptors has been questioned, recent evidence suggests that alpha stimulation may play a role in cold air- and exercise-induced asthma. Finally, non-adrenergic, non-cholinergic nerves have been shown to cause relaxation of human airways in in vivo studies. There is increasing evidence that vasoactive intestinal peptide and peptide histidine methanol are the mediators of these responses. More recently, other neuropeptides (substance P, neurokinin A, and calcitonin gene-related peptide) have been localized in nerves in airways. These cause bronchoconstriction in vitro and may be released from afferent nerve terminals by an axon reflex. Although the precise role of these substances in controlling airway tone and bronchial secretions in humans is not fully understood, they may have important modulatory effects on the neural control of airway function.

PMID: 2878614 [PubMed - indexed for MEDLINE]

Trigeminocardiac reflex. A clinical phenomenon or a new physiological entity?

J Neurol. 2004 Jun;251(6):658-65.

Schaller B.
Max-Planck-Institute for Neurological Research, Gleueler Strasse 50, 50931 Cologne, Germany.

The trigemino-cardiac reflex (TCR) is defined as the sudden onset of parasympathetic dysrhythmia, sympathetic hypotension, apnea or gastric hypermotility during stimulation of any of the sensory branches of the trigeminal nerve.

The sensory nerve endings of the trigeminal nerve send neuronal signals via the Gasserian ganglion to the sensory nucleus of the trigeminal nerve, forming the afferent pathway of the reflex arc. This afferent pathway continues along the short internuncial nerve fibers in the reticular formatio to connect with the efferent pathway in the motor nucleus of the vagus nerve.

Clinically, the trigemino-cardiac reflex has been reported to occur during craniofacial surgery, balloon-compression rhizolysis of the trigeminal ganglion, and tumor resection in the cerebellopontine angle. Apart from the few clinical reports, the physiological function of this brainstem-reflex has not yet been fully explored.

From experimental findings, it may be suggested that the trigemino-cardiac reflex represents an expression of a central neurogenic reflex leading to rapid cerebrovascular vasodilatation generated from excitation of oxygen-sensitive neurons in the rostral ventrolateral medulla oblongata. By this physiological response, the adjustments of the systemic and cerebral circulations are initiated to divert blood to the brain or to increase blood flow within it. As it is generally accepted that the diving reflex and ischemic tolerance appear to involve at least partially similar physiological mechanisms, the existence of such endogenous neuroprotective strategies may extend the actually known clinical appearance of the TCR and include the prevention of other potentially brain injury states as well.

This may be in line with the suggestion that the TCR is a physiological, but not a pathophysiological entity.

PMID: 15311339 [PubMed - indexed for MEDLINE]

Neural control of airway vasculature and edema.

Am Rev Respir Dis. 1991 Mar;143(3 Pt 2):S18-21.

Widdicombe JG.

Department of Physiology, St. George's Hospital Medical School, London, United Kingdom.
The tracheobronchial vasculature is controlled by adrenergic, cholinergic, and peptidergic nervous mechanisms. Sympathetic nerves release norepinephrine and neuropeptide Y (NPY), which are both constrictor agents, the latter being long-lasting. Parasympathetic nerves release acetylcholine and usually vasoactive intestinal polypeptide (VIP), both of which are vasodilators, VIP being the longer lasting. These motor nerves are controlled by many reflex inputs. Activation of pulmonary C-fiber receptors by irritants and inflammatory mediators causes a powerful vasodilatation, mainly via sympathetic motor nerves. Cardiac and chemoreceptor reflexes also influence airway vascular tone. Sensory nerves in the airway mucosa are responsible for local axon reflexes in response to irritants and inflammatory mediators. These nerves contain neuropeptides such as substance P (SP), neurokinins A and B (NKA, NKB), and calcitonin gene-related peptide (CGRP). All these neuropeptides are powerful vasodilators. Thus, inflammatory conditions in the lungs such as asthma cause vasodilation by local direct action of mediators, by axon reflexes, and by central nervous reflexes. The vasodilation could lead to mucosal edema. Thus, airway vascular responses have to be added to bronchoconstriction and mucus secretion as part of the mucosal pathology of asthma.

PMID: 2003685 [PubMed - indexed for MEDLINE]

The trigemino-cardiac reflex: an update of the current knowledge.

J Neurosurg Anesthesiol. 2009 Jul;21(3):187-95.
Schaller B, Cornelius JF, Prabhakar H, Koerbel A, Gnanalingham K, Sandu N, Ottaviani G, Filis A, Buchfelder M; Trigemino-Cardiac Reflex Examination Group (TCREG).

Department of Neurosurgery, University of Paris, France. skull_base_surgery@yahoo.de

The trigemino-cardiac reflex (TCR) is clinically defined as the sudden onset of parasympathetic activity, sympathetic hypotension, apnea, or gastric hypermotility during central or peripheral stimulation of any of the sensory branches of the trigeminal nerve.

Clinically, the TCR has been reported to occur during craniofacial surgery, manipulation of the trigeminal nerve/ganglion and during surgery for lesion in the cerebellopontine angle, cavernous sinus, and the pituitary fossa. Apart from the few clinical reports, the physiologic function of this brainstem reflex has not yet been fully explored. The manifestation of the TCR can vary from bradycardia and hypotension to asystole. From the experimental findings, the TCR represents an expression of a central reflex leading to rapid cerebrovascular vasodilatation generated from excitation of oxygen-sensitive neurons in the rostral ventro-lateral medulla oblongata. By this physiologic response, the systemic and cerebral circulations may be adjusted in a way that augments cerebral perfusion. This review summarizes the current state of knowledge about TCR.

PMID: 19542994 [PubMed - indexed for MEDLINE]

Neuroregulation of the nose and bronchi.

Clin Exp Allergy. 1996 May;26 Suppl 3:32-5.
Widdicombe JG.
Department of Physiology, St George's Hospital Medical School, London, UK.

The vascular beds, submucosal glands, and airway vasculature are the three primary effector tissues in the airways, and all are under the control of the parasympathetic (vagal) and sympathetic nervous systems. Parasympathetic nerves play a more important role in smooth muscle contraction and gland secretion. The complex neurogenic mechanisms initiated by activation of sensory nerves have been clarified to a large extent by studies on experimental animals. For example, inflammation or an allergic response will cause neurogenic inflammation due to axon reflexes; central nervous reflexes will modulate activity in all of the effector tissues; and these reflex responses will be modulated by local reflexes via parasympathetic ganglia. Similar mechanisms are suspected in humans, but their importance still needs to be fully established.

PMID: 8735856 [PubMed - indexed for MEDLINE]

The falcine trigeminocardiac reflex: case report and review of the literature.

Surg Neurol. 2005 Feb;63(2):143-8.

Bauer DF, Youkilis A, Schenck C, Turner CR, Thompson BG.

University of Michigan Medical School, Ann Arbor, MI 48109, USA.
BACKGROUND: Trigeminocardiac reflex (TCR), the reproducible hypotension and bradycardia upon stimulation of the trigeminal nerve, has been reported during craniofacial surgery and during surgery within the cerebellopontine angle, petrosal sinus, orbit, and trigeminal ganglion. Whereas the falx cerebri is known to be innervated by the nervus tentorii, a recurrent branch of V1, there have been no reports to date of this response upon mechanical stimulation of the falx. CASE DESCRIPTION: We report a case of immediate, reproducible, and reflexive response of asystole upon stimulation of the falx cerebri during operative resection of a parafalcine meningioma in a 53-year-old woman. Upon recognition of the reproducible relationship between falcine stimulation and increased vagal tone, the patient was given glycopyrrolate in an effort to block cholinergic hyperactivity. After glycopyrrolate was given, no further dysrhythmias occurred.

CONCLUSION: In this patient, mechanical stimulation of the falx likely resulted in the hyperactivity of the trigeminal ganglion, thereby triggering TCR. The dorsal region of the spinal trigeminal tract includes neurons from hypoglossal and vagus nerves, and projections have been seen between the vagus and trigeminal nuclei. The vagus provides parasympathetic innervation to the heart, vascular smooth muscle, and abdominal viscera. Vagal stimulation via these connections after trigeminal nerve activation likely accounts for the reflexive response of asystole seen in this patient. This is confirmed by the observation that the reflex was inhibited by the anticholinergic effects of glycopyrrolate. Awareness of TCR allows for early detection and appropriate treatment.

PMID: 15680656 [PubMed - indexed for MEDLINE]

The physiology of the nose

Clin Chest Med. 1986 Jun;7(2):159-70.
.
Widdicombe JG.

The nose, as an organ initiating reflexes affecting itself and the rest of the body, and as a target organ of control, is highly complex. Its innervation includes parasympathetic, sympathetic, sensory/afferent, and somatic motor nerves, which combine in a variety of morphologic pathways. The vasculature of the nose contains capacitance vessels such as sinusoids and distensible venules, as well as arteriovenous anastomoses, arterioles, capillaries, and venules. The secretory tissue of the nose includes epithelial cells, submucosal glands, and relatively large anterior or lateral serous glands; in addition, some species have specialized secretory glands. The nose is the source of many powerful reflexes, including the diving response, sneeze and sniff reflexes, and reflexes affecting autonomic nervous function to the cardiovascular system, airways in the lungs, the larynx, and other organs. Axon reflex control of the nasal vasculature is also important. The nasal vasculature can be shown to be under parasympathetic and sympathetic control, but there is little precise information concerning the effect of nerves on different types of blood vessels. Pharmacologic experiments show that vascular resistance and vascular volume can be separately influenced by nerves and mediators, and that vascular resistance and airway resistance are not necessarily inversely related. Nasal secretion is also under the influence of both parasympathetic and sympathetic nerves, and can be induced by a wide range of neurotransmitters and mediators. In general, the concentrations needed to promote secretion are considerably higher than those that affect vascular resistance, at least with regard to the lateral nasal gland of the dog. In humans, nasal patency is affected by several nervous inputs, presumably acting via vascular beds. The nasal cycle is the alternation of resistances between the two sides of the nose, on which other changes are superimposed. In exercise and hyperpnea, nasal airflow resistance decreases, presumably with vascular decongestion. Recent studies of the crutch reflex (the ipsilateral nasal congestion caused by stimulation of the axilla) show that some of the reflex inputs to the nose can be unilateral.

PMID: 3522066 [PubMed - indexed for MEDLINE]

Trigeminocardiac reflex: a MaxFax literature review

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Aug;108(2):184-8.
Bohluli B, Ashtiani AK, Khayampoor A, Sadr-Eshkevari P.

Oral and Maxillofacial Surgery, School of Dental Medicine, Azad University of Tehran, Tehran, Iran.
Trigeminocardiac reflex (TCR) is a shocking event in the course of operation involving the maxillofacial area. The authors have tried to present an overview on the history, clinical implications, literature review, anatomic and biologic basis, predisposing and triggering factors, and management of the event. Being familiar with the presentations, preventive measures, and management procedures are seemingly the most important aspects of the TCR to oral and maxillofacial surgeons and anesthesiologists.

PMID: 19615657 [PubMed - indexed for MEDLINE]

Nasonasal reflexes, the nasal cycle, and sneeze

Curr Allergy Asthma Rep. 2007 May;7(2):105-11.
Baraniuk JN, Kim D.

Division of Rheumatology, Immunology and Allergy, Room B105, Lower Level Kober-Cogan Building, Georgetown University, 3800 Reservoir Road, NW, Washington, DC 20007-2197, USA. baraniuj@georgetown.edu
The nasal mucosa is a complex tissue that interacts with its environment and effects local and systemic changes. Receptors in the nose receive signals from stimuli, and respond locally through afferent, nociceptive, type C neurons to elicit nasonasal reflex responses mediated via cholinergic neurons. This efferent limb leads to responses in the nose (eg, rhinorrhea, glandular hyperplasia, hypersecretion with mucosal swelling). Anticholinergic agents appear useful against this limb for symptomatic relief of a "runny nose." Chronic exposure to allergens can lead to hyperresponsiveness of the nasal mucosa. As a result, receptors upregulate specific ion channels to increase the sensitivity and potency of their reflex response. Nasal stimuli also affect distant parts of the body. Nerves in the sinus mucosa cause vasodilation; the lacrimal glands can be stimulated by nasal afferent triggers. Even the cardiopulmonary system can be affected via the trigeminal chemosensory system, where sensed irritants can lead to changes in tidal volume, respiratory rate, and blink frequency. The sneeze is an airway defense mechanism that removes irritants from the nasal epithelial surface. It is generally benign, but can lead to problems in certain circumstances. The afferent pathway involves histamine-mediated depolarization of H1 receptor-bearing type C trigeminal neurons and a complex coordination of reactions to effect a response.

PMID: 17437680 [PubMed - indexed for MEDLINE]

Nasal-cardiac reflex

Otolaryngol Pol. 2003;57(5):613-8.
[Article in Polish]
Betlejewski S, Betlejewski A, Burduk D, Owczarek A.

Katedra i Klinika Otolaryngologii AM w Bydgoszczy.
The nasocardiac reflex is a little known reaction of nasomucosal origin. The nasocardiac reflex itself may lead to severe bradycardia or can even procure a very dramatic cardiac arrest following irritation or stimulation of the nerves in the nasal cavities or paranasal sinuses. To clarify the rules and mechanisms of the stimulation of the nasal mucosa influencing heart function, 80 healthy volunteers underwent the experiment. After stimulation of the nasal mucosa on the media turbinates by means of 25% ammonia, almost all individuals revealed a significant decrease in the heart rate. In 11 volunteers, disturbances in heart rhythm occurred after a short period of apnoea. Investigations were performed also in 54 persons before and after local anesthesia of the nasal mucosa by means of 2% lignocaine. In 80% of investigated the local anesthesia did not influence the nasocardiac reflex. Analyzing the influence of the preoperative premedication in 26 patients, it was observed, that the reflective reaction after premedication was more expressed than before. Because laryngectomy changes the conditions and physiology of the nose as the first part of the respiratory tract, the nasocardiac reflex in 38 laryngectomized patients was also analyzed. Tests were carried out preoperatively and postoperatively several days, months and years after surgery. Respiratory and heart function were registered synchronically, a flowmeter before operation was placed in one nostril and postoperatively in the tracheostomy tube. May be that such speedy heart reaction on nasal mucosa stimulation is connected with the participation of vagal nerve branches in the spheno-palatine ganglion.
 PMID: 14994602 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/14994602

Parasympathetic overactivity in patients with nasal septum deformities

European Archives of Oto-Rhino-Laryngology
 Volume 267, Number 1 / January, 2010
Baran Acar1 , Bunyamin Yavuz2, Hayriye Karabulut1, Emre Gunbey1, Mehmet Ali Babademez1, Ahmet Arif Yalcin2 and Murat Karaşen1(1) Department of Otorhinolaryngology, Kecioren Training and Research Hospital, Pınarbaşı Mahallesi Sanatoryum Caddesi Ardahan Sok. No. 1, Keçiören, 06310 Ankara, Turkey
(2) Department of Cardiology, Kecioren Training and Research Hospital, Ankara, Turkey


Received: 5 December 2008 Accepted: 10 July 2009 Published online: 24 July 2009
Abstract Nasal septum deformities (NSD) are one of the most frequent reasons for nasal obstruction presented with a reduction in nasal airflow and chronic mucosal irritation. Nasocardiac reflex which includes afferent stimulus with maxillary division of the trigeminal nerve and the efferent pathway of the heart via the vagus nerve is not a well-known part of autonomic nervous system (ANS). Heart rate variability (HRV) is a parameter reflecting the ANS activity on heart. The purpose of this study is to evaluate ANS functions in patients with NSD by HRV analysis. Twenty-nine patients with NSD and 26 control subjects were included in the study. The diagnosis of NSD was made with history, symptoms, anterior rhinoscopy, and nasal endoscopic examination. 24-h ambulatory electrocardiographic recording was performed by a 3-channel recorder. HRV parameters were obtained by analyzing these parameters. Baseline features were similar in patients and controls (mean age: 31 ± 8 in the patients, 32 ± 9 in control subjects; P = NS). Night-RMSSD (the square root of square of mean square differences of successive NN intervals) (47 ± 21, 34 ± 13; P = 0.008), night-PNN50 (the number of interval differences of successive NN intervals greater than 50 ms) (24 ± 16, 14 ± 10; P = 0.007), 24-h-RMSSD (39 ± 18, 27 ± 12; P = 0.004), and 24-h-PNN50 (16 ± 12, 9 ± 7; P = 0.016) were significantly higher in patients than controls. Other HRV parameters were not significantly different between two groups. Changes in these parameters demonstrated an increased parasympathetic tone and discordance in sympatho-vagal activity in NSD.

The effect of topical ciprofloxacin and steroid-containing ear drops for chronic suppurative otitis media on the internal ear

 European Archives of Oto-Rhino-Laryngology
Volume 267, Number 1 / January, 2010
Zeliha Kapusuz1, Erol Keles1, Hayrettin Cengiz Alpay1 , Turgut Karlidag1, Irfan Kaygusuz1, Ali Kemal Uzunlar2, Israfil Orhan1 and Sinasi Yalcin1(1) Department of Otorhinolaryngology, Firat University Medical Faculty, 23200 Elazig, Turkey
(2) Department of Pathology, Duzce University Medical Faculty, Duzce, Turkey


Received: 19 March 2009 Accepted: 4 June 2009 Published online: 25 June 2009
Abstract Aim of the study is to evaluate the effects of topical ciprofloxacin and prednisolone-containing ear drops for chronic suppurative otitis media on hearing threshold, cochlear reserve and cochlea morphology in healthy subjects and to determine the proper drug dose. Sixty-eight guinea pigs, all of which had healthy hearing, were used for the study. The first group (n = 30) was administered ciprofloxacin three times a day, the second group (n = 30) was administered prednisolone three times a day and the third group (n = 8) was administered sterile distilled water three times a day. The therapies lasted for 7 days and were administered intratympanically. The first group and second group were divided into three sub-groups of ten subjects. The first sub-group (n = 10) was administered an equivalent dose per kilogram as in humans, the second sub-group (n = 10) was administered one-third of the human-equivalent dose and the third sub-group (n = 10) was administered tenfold the human-equivalent dose. All subjects underwent brainstem evoked response audiometry (BERA) and distortion product otoacoustic emission (DPOAE) testing on the seventh and twenty-first days following the therapy. Following the tests, two subjects from each group were decapitated and examined under electron microscope. BERA and DPOAE testing results of the sub-group (n = 10) which was administered tenfold the human-equivalent dose were significantly different from the control group and other groups (P < 0.05). According to electron microscopic examination of the cochlea, the group which was administered a tenfold human-equivalent dose of intratympanic ciprofloxacin and prednisolone showed atrophy in cells and degenerations in cilia. This case was statistically significant when compared with the control group and other groups (P < 0.05).
Ciprofloxacin and prednisolone applied at a human-equivalent dose per kilogram did not affect the hearing and cochlear histology of subjects.

Drug Profile: Montelukast in the treatment of asthma and beyond

Expert Review of Clinical Immunology
November 2009, Vol. 5, No. 6, Pages 639-658 , DOI 10.1586/eci.09.62
Zuzana Diamant†, Eva Mantzouranis and Leif Bjermer
†Author for correspondence


Asthma is a chronic inflammatory disease affecting over 300 million people worldwide. The common association with allergic rhinitis and the presence of proinflammatory cells and mediators in the circulation of patients qualify asthma as a systemic disease. This characteristic and the fact that the gold-standard therapy for persistent asthma, inhaled corticosteroids, cannot suppress all components of airway inflammation and fail to adequately penetrate into the small airways, warrant the quest for effective systemic anti-asthma therapies. This review describes the most important controlled studies of montelukast, a once-daily leukotriene receptor antagonist, in asthma and allergic rhinitis in both adults and children. Montelukast is a systemically active drug with a targeted, dual mechanism of action, acting both as a bronchodilator and anti-inflammatory. In patients of all ages, montelukast has shown a favorable safety profile and was well-tolerated. Both as monotherapy or in combination with inhaled corticosteroids, montelukast produced clinically relevant improvements in asthma-related parameters, including symptoms, lung function parameters, quality of life and the number of asthma exacerbations. Furthermore, bronchoprotective effects have been reported both against specific and nonspecific bronchoactive stimuli. Similarly, in patients with allergic rhinitis, montelukast produced substantial improvements in symptoms and quality of life. Long-term studies aimed to determine its effects on airway remodeling are still lacking.

Parasympathetic overactivity in patients with nasal septum deformities

European Archives of Oto-Rhino-LaryngologyVolume 267, Number 1 / January, 2010
Baran Acar1 , Bunyamin Yavuz2, Hayriye Karabulut1, Emre Gunbey1, Mehmet Ali Babademez1, Ahmet Arif Yalcin2 and Murat Karaşen1
 (1) Department of Otorhinolaryngology, Kecioren Training and Research Hospital, Pınarbaşı Mahallesi Sanatoryum Caddesi Ardahan Sok. No. 1, Keçiören, 06310 Ankara, Turkey.  (2) Department of Cardiology, Kecioren Training and Research Hospital, Ankara, Turkey 

Abstract Nasal septum deformities (NSD) are one of the most frequent reasons for nasal obstruction presented with a reduction in nasal airflow and chronic mucosal irritation. Nasocardiac reflex which includes afferent stimulus with maxillary division of the trigeminal nerve and the efferent pathway of the heart via the vagus nerve is not a well-known part of autonomic nervous system (ANS). Heart rate variability (HRV) is a parameter reflecting the ANS activity on heart. The purpose of this study is to evaluate ANS functions in patients with NSD by HRV analysis. Twenty-nine patients with NSD and 26 control subjects were included in the study. The diagnosis of NSD was made with history, symptoms, anterior rhinoscopy, and nasal endoscopic examination. 24-h ambulatory electrocardiographic recording was performed by a 3-channel recorder. HRV parameters were obtained by analyzing these parameters. Baseline features were similar in patients and controls (mean age: 31 ± 8 in the patients, 32 ± 9 in control subjects; P = NS). Night-RMSSD (the square root of square of mean square differences of successive NN intervals) (47 ± 21, 34 ± 13; P = 0.008), night-PNN50 (the number of interval differences of successive NN intervals greater than 50 ms) (24 ± 16, 14 ± 10; P = 0.007), 24-h-RMSSD (39 ± 18, 27 ± 12; P = 0.004), and 24-h-PNN50 (16 ± 12, 9 ± 7; P = 0.016) were significantly higher in patients than controls. Other HRV parameters were not significantly different between two groups. Changes in these parameters demonstrated an increased parasympathetic tone and discordance in sympatho-vagal activity in NSD.

Personal experience with tinnitus retraining therapy

European Archives of Oto-Rhino-Laryngology Volume 267, Number 1 / January, 2010
Egisto Molini1, Mario Faralli1 , Claudio Calenti1, Giampietro Ricci1, Fabrizio Longari1 and Antonio Frenguelli1  (1) Otolaryngology and Cervicofacial Surgery Clinic, University of Perugia, Perugia, Italy 

Abstract We present the results of tinnitus retraining therapy (TRT) in a group of patients suffering from tinnitus and/or hyperacusia. Based on the scores from a specific questionnaire and the Tinnitus Handicap Inventory (THI), the patients were classified into five categories and began therapy according to Jastreboff’s criteria. Depending on the individual case, therapy envisaged counselling sessions, ambient sound enrichment, sound generators and hearing aids. At the end of the 18-month period, therapeutic success was observed in 79% of the patients. The initial numerical values of the scale of the symptoms and the THI seem predictive of treatment outcome. The use of instruments (sound generators) increases the success rate, but the study also demonstrates the effectiveness of counselling and ambient sound enrichment. Failures mainly involved patients with hypacusia who refused to wear hearing aids, as this influenced the effectiveness of ambient sound enrichment and counselling. Paralleling the data in the literature, the results demonstrate the effectiveness of TRT, which cannot be attributed to a placebo effect given the extended duration of treatment.

Vascular Endothelial Growth Factor Drives Autocrine Epithelial Cell Proliferation and Survival in Chronic Rhinosinusitis with Nasal Polyposis

American Journal of Respiratory and Critical Care Medicine Vol 180. pp. 1056-1067, (2009)
© 2009 American Thoracic Society

Hyun Sil Lee1, Allen Myers1 and Jean Kim1,2

1 Department of Allergy and Clinical Immunology and 2 Department of Otolaryngology, Head and Neck Surgery, Johns Hopkins Asthma and Allergy Center, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, Maryland

Correspondence and requests for reprints should be addressed to Jean Kim, M.D., Ph.D., Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Room 3B65A, Baltimore, MD 21224. E-mail: jeankim@jhmi.edu

Rationale: The pathogenesis of nasal polyps in chronic rhinosinusitis is poorly understood.

Objectives: These studies seek to implicate a functional role for vascular endothelial growth factor (VEGF) in perpetuating primary nasal epithelial cell overgrowth, a key feature of hyperplastic polyps.

Methods: Comparison of VEGF and receptor expression was assessed by ELISA of nasal lavage, immunohistochemistry of sinus tissue, flow cytometry of nasal epithelial cells, and ELISA of supernatants. VEGF-dependent cell growth and apoptosis were assessed with blocking antibodies to VEGF, their receptors, or small interfering RNA knockdown of neuropilin-1 by cell proliferation assays and flow cytometric binding of annexin V.

Measurements and Main Results: VEGF protein was sevenfold higher in nasal lavage from patients with polyposis compared with control subjects (P < 0.001). We also report elevated expression of VEGF (P < 0.012), receptors VEGFR2 and phospho-VEGFR2 (both P < 0.04), and identification of VEGF coreceptor neuropilin-1 in these tissues. Nasal epithelial cells from patients with polyps demonstrated faster growth rates (P < 0.005). Exposure of cells to blocking antibodies against VEGF resulted in inhibition of cell growth (P < 0.05). VEGF receptor blockade required blockade of neuropilin-1 (P < 0.05) and resulted in increased apoptosis (P < 0.001) and inhibition of autocrine epithelial VEGF production (P < 0.05).

Conclusions: These data demonstrate that VEGF is a novel biomarker for chronic rhinosinusitis with hyperplastic sinonasal polyposis that functions in an autocrine feed-forward manner to promote nasal epithelial cell growth and to inhibit apoptosis. These findings implicate a previously unrecognized and novel role of VEGF functioning through neuropilin-1 on nonneoplastic primary human airway epithelial cells, to amplify cell growth, contributing to exuberant hyperplastic polyposis.
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AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Chronic rhinosinusitis with nasal polyposis is a disease characterized by recurrent and recalcitrant hyperplastic polyp growth, the pathogenesis of which is poorly understood.

What This Study Adds to the Field
These studies define a novel role for vascular endothelial growth factor as an autocrine epithelial cell mitogen and prosurvival factor that drives the epithelial cell hyperplasia observed in hyperplastic chronic rhinosinusitis with nasal polyposis.

Heightened cough sensitivity secondary to latanoprost

Chest 136 (5), 1406-7 (Nov 2009)

Fahim A, Morice AH; 

Chronic cough is a common symptom with significant morbidity. We report a case of a 51-year-old woman who presented with chronic cough. She recently had received a diagnosis of glaucoma and had started receiving therapy with topical latanoprost. The onset of cough coincided with the use of latanoprost. We performed a citric acid cough challenge while the patient was receiving latanoprost and repeated the challenge after therapy with the drug was stopped. The initial cough challenge revealed marked hypersensitivity of the cough reflex. After stopping therapy with latanoprost for 10 days, the cough sensitivity was reduced significantly. Within 3 days of recommending therapy with latanoprost, the cough sensitivity increased to the initial value. This case illustrates that the topical application of latanoprost can markedly increase cough sensitivity, which is reversible on stopping administration of the drug. Moreover, the case reflects the clinical manifestation of the effect of topical latanoprost therapy on cough reflex, which, to our knowledge, has never been reported in the medical literature.

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Clinical Studies of Combination Montelukast and Loratadine in Patients with Seasonal Allergic Rhinitis

Journal of Asthma, Volume 46, Issue 9 November 2009 , pages 878 - 883

Authors: Susan Lu ^a;  Marie-Pierre Malice ^b;  S. Balachandra Dass ^a; Theodore F. Reiss ^a

Affiliations:	a Merck Research Laboratories, Clinical Research, Rahway, New Jersey, USA
	b Merck Research Laboratories, Brussels, Belgium

Abstract

Background. Concomitant use of montelukast and loratadine may improve symptoms of seasonal allergic rhinitis (SAR) more than treatment with either drug alone. Objective. We compared the efficacy of this combination versus placebo, nasal beclomethasone, montelukast, and loratadine in study 1 and versus placebo, montelukast, and loratadine in study 2. Methods. Patients were randomly allocated to double-blind treatment with intranasal beclomethasone 200 μ g/twice daily (study 1 only), placebo, montelukast 10 mg+loratadine 10 mg, montelukast 10 mg, or loratadine 10 mg once daily. The primary endpoint was the Composite Symptom Score (CSS): average of daily diary scores for Daytime Nasal Symptoms and Nighttime Symptoms. Results. In study 1, improvements in the change from baseline in CSS were seen for montelukast+loratadine (least-squares means [95% CI] = -0.43 [-0.51, -0.35]), beclomethasone (-0.57 [-0.64, -0.49]), montelukast, and loratadine. All treatments were significantly better than placebo; montelukast+loratadine had a significantly greater effect on CSS than montelukast alone but no difference compared to loratadine was detected. Beclomethasone provided significantly greater improvement versus montelukast+loratadine on the primary and secondary endpoints except for the rhinoconjunctivitis quality-of-life score. In study 2, the combination treatment was similar to montelukast, loratadine, and placebo for the primary and secondary endpoints. Conclusion. In study 1, montelukast+loratadine had a significantly greater effect on CSS than placebo and montelukast alone; however, in all comparisons, nasal beclomethasone had a greater effect on daily symptoms. In contrast, the combination of montelukast+loratadine in study 2 did not provide greater improvement compared with placebo, montelukast, or loratadine monotherapy, perhaps due to a large placebo effect.

Minimal persistent inflammation in allergic rhinitis: implications for current treatment strategies

REVIEW ARTICLE

Clinical & Experimental Immunology

Volume 158 Issue 3, Pages 260 - 271

Published Online: 25 Aug 2009
Journal Compilation © 2008 British Society for Immunology

G. W. Canonica and E. Compalati

Allergy and Respiratory Diseases, Clinic Dipartmento di Medicina Interna e Specialita Mediche (DIMI), University of Genova, Genova, Italy

Correspondence to G. W. Canonica, Allergy and Respiratory Diseases, Clinic Dipartmento di Medicina Interna e Specialita Mediche (DIMI), University of Genova, Viale Benedetto XV, no. 6, 16132 Genova, Italy.
E-mail: canonica@unige.it

ABSTRACT

Patients with allergic rhinitis have traditionally been placed into 'seasonal' and 'perennial' categories, which do not account for the subclinical inflammatory state that exists in many patients. In subjects with seasonal and perennial allergic rhinitis, even subthreshold doses of allergen have been found to cause inflammatory cell infiltration in the nasal mucosa, including increases in expression of cellular adhesion molecules, nasal and conjunctival eosinophilia, and other markers of inflammation, which do not result in overt allergy symptoms. This state – which has been termed 'minimal persistent inflammation'– may contribute to hyperreactivity and increased susceptibility to development of clinical symptoms as well as common co-morbidities of allergic rhinitis, such as asthma. Treating overt allergy symptoms as well as this underlying inflammatory state requires agents that have well-established clinical efficacy, convenient administration, potent anti-inflammatory effects and proven long-term safety, so that long-term continuous administration is feasible.

Of the three major classes of commonly used allergic rhinitis medications – intranasal corticosteroids, anti-histamines, and anti-leukotrienes – intranasal corticosteroids appear to represent the most reasonable therapeutic option in patients who would benefit from continuous inhibition of persistent inflammation.

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Accepted for publication 14 August 2009