The effect of proton pump inhibitors on the human microbiota.

Proton pump inhibitors (PPIs) are commonly used to treat acid-related diseases, most notably gastroesophageal reflux disease. PPIs are designed to shut down the gastric proton pump (H+/K+-ATPase) of parietal cells, thereby raising the pH of the stomach. While effective, a number of side effects have been associated with PPI use. Naturally occurring bacteria, some of which are acid-producing and contain ATPase enzymes, have also been found within the stomach, upper gastrointestinal tract, and oral cavity. Likewise, a number of fungi are known to inhabit the human body; some of these fungi contain H+-ATPase enzymes. Recent literature has suggested that PPIs may be inadvertently affecting these bacteria and fungi in two different ways: 1) PPIs may directly target the proton pumps of the bacteria and fungi, and/or 2) PPIs may indirectly affect the microenvironment of the flora via changes in pH. These unintended interactions are exasperated by the systemic distribution of PPIs throughout the body and may potentially lead to some of the side effects observed with PPI use. Herein we summarize what is currently known about the interactions between the PPIs and the natural human microbiota.

Spatial tuning curves along the chick basilar papilla in normal and sound-exposed ears.

Intense sound exposure destroys chick short hair cells and damages the tectorial membrane. Within a few days postexposure, signs of repair appear resulting in nearly complete structural recovery of the inner ear. Tectorial membrane repair, however, is incomplete, leaving a permanent defect on the sensory surface. The consequences of this defect on cochlear function, and particularly frequency analysis, are unclear. The present study organizes the sound-induced discharge activity of cochlear nerve units to describe the distribution of neural activity along the tonotopic axis of the basilar papilla. The distribution of this activity is compared in 12-day postexposed and age-matched control groups. Spontaneous activity, tuning curves, and rate-intensity functions were measured in each unit. Discharge activity at 60 frequency and intensity combinations was identified in the tuning curves of hundreds of units. Activity at each of these criterion frequency/intensity combinations was plotted against the unit's characteristic frequency to construct spatial tuning curves (STCs). The STCs depict tone-driven cochlear nerve activity along the length of the papilla. Tuning sharpness, low- and high- frequency slopes, and the maximum response were quantified for each STC. The sharpness of tuning increased with increasing criterion frequency. However, within a frequency, increasing sound intensity yielded more broadly tuned STCs. Also, the high-frequency slope was consistently steeper than the low-frequency slope. The STCs of exposed ears exhibited slightly less frequency selectivity than control ears across all frequencies and larger maximum responses for STCs with criterion frequencies spanning the tectorial membrane defect. When rate-intensity types were segregated, differences were observed in the STCs between saturating and sloping-up units. We propose that STC shape may be determined by global mechanical events, as well as localized tuning and nonlinear processes associated with individual hair cells. The results indicated that 12 days after intense sound exposure, global and local contributions to spatially distributed neural activity are restored.

Paradoxical vocal fold motion: presentation and treatment options.

Paradoxical vocal fold motion is a rare disorder in which adduction of the folds occurs on inspiration. The disorder presents with signs of airway obstruction and often airway distress, so proper diagnosis by the otorhinolaryngologist is critical to subsequent management. We present a retrospective review of 10 patients with the diagnosis of paradoxical vocal fold motion seen over a 6-year period. Eight patients were females, and 6 required an acute airway intervention at presentation; 3 patients eventually underwent tracheotomy for respiratory decompensation. Six patients had a prior diagnosis of asthma, and this was determined to contribute to their respiratory status. Five patients were treated with botulinum toxin and 2 with flexible nasolaryngoscopic biofeedback, which improved the outcome. A review of the literature confirms a female predominance of patients presenting with paradoxical adduction and airway distress, often with a history of asthma and psychopathology. Our experience with botulinum toxin and biofeedback suggests that these procedures are viable treatment options in the management of patients with this disorder.

Congenital airway abnormalities in patients requiring hospitalization.

OBJECTIVE: To determine the cause of congenital airway abnormalities in pediatric patients requiring hospitalization for their respiratory status. DESIGN AND SETTING: Case series in a tertiary care center. PATIENTS: A 5-year retrospective chart review was conducted at our institution. A total of 174 patients were identified who required hospitalization for their respiratory status as a result of a congenital airway abnormality. RESULTS: Of the 174 patients, 114 (65.5%) were male and 60 (34.5%) were female. Eighty patients (47%) presented within the first 3 months of life. Forty-six patients (26%) were born prematurely, and 49 patients (28%) were diagnosed as having gastroesophageal reflux. The majority of patients (139 [80%]) had multiple presenting symptoms or signs. Stridor was the most common (129 [74%]), followed by accessory respiratory effort, cyanosis, apnea, and failure to thrive. Diagnosis was made at the time of surgical evaluation in 91% of the patients, with the remaining diagnoses made using radiological findings and/or clinical evaluation. Sixty-five patients (37%) had multiple sites of airway abnormalities; laryngeal abnormalities were noted almost 3 times as often as tracheal abnormalities (161 vs 62, respectively). Of the laryngeal abnormalities, laryngomalacia was the most common, followed by glottic web, subglottic stenosis, vocal-cord paralysis, and subglottic hemangioma. Tracheomalacia was the most common tracheal abnormality, followed by external compression and tracheal stenosis. Thirty-three patients (19%) required tracheotomy for management of recurrent respiratory decompensation. CONCLUSIONS: While congenital airway abnormalities are usually self-limited, those patients requiring hospitalization represent a group with a more severe respiratory status who have a greater chance of requiring tracheotomy. The recognizable percentage of patients with gastroesophageal reflux and prematurity accounts for comorbid factors in the need for hospitalization for respiratory issues related to congenital airway abnormalities.

Angioedema presenting in the retropharyngeal space in an adult.

PURPOSE: Hereditary angioedema is a rare disorder of deficient or dysfunctional C1-esterase inhibitor and usually manifests as edema of the face, tongue, supraglottis, extremities, or gastrointestinal tract. We report the case of a 40-year-old man with known hereditary angioedema who presented with a sore throat and a sensation of evolving airway obstruction. After a thorough search of the medical literature, we believe this to be the first reported case of angioedema manifesting in the retropharyngeal space. The pathophysiological factors of angioedema are discussed, along with its variable presentation and management issues. METHOD: Laryngoscopic examination was suggestive of posterior pharyngeal fullness; therefore, a computed tomographic scan of the neck was obtained, which showed a non-contrast-enhancing retropharyngeal edema from the base of the skull to below the level of the glottis. The patient had a history of multiple episodes of angioedema requiring hospitalization and three prior tracheotomies. RESULTS: Familiarity with the patient's history directed his rapid treatment course (including intravenous stanozolol, Solu-Medrol, and diphenhydramine), which significantly reduced his edema and avoided the need for tracheotomy. CONCLUSION: Hereditary angioedema may present in atypical locations, and expeditious treatment in a patient with a known history may avert the sequelae of evolving airway obstruction.

Comparison of endoscopy and radiographic fluoroscopy in the evaluation of pediatric congenital airway abnormalities.

In order to assess the accuracy of conventional dynamic radiographic studies compared to endoscopy in the diagnosis of congenital airway abnormalities, we performed a retrospective chart review for the period between July 1991 to June 1996. A total of 186 patients were identified who required hospitalization for their respiratory status as a result of a congenital airway abnormality. Of these, 19% had both endoscopy and conventional dynamic radiographic evaluation (airway fluoroscopy, barium esophagography, or both). Eleven percent had fluoroscopy only, 62% had endoscopy only, and 9% had neither. In those patients who underwent both endoscopic and conventional dynamic radiographic evaluation, endoscopy was considered to be the definitive procedure for diagnosis. Laryngomalacia was present in 94% of these patients. Thirteen patients had multiple sites of airway abnormalities on endoscopy, and a total of 51 abnormalities were identified. Dynamic radiographic evaluation was correct in four, was suggestive of the abnormality in 12, did not recognize an abnormality in 33, and suggested a different diagnosis (not corresponding to endoscopy) in two. Thus, airway fluoroscopy and/or barium esophagography were correct or suggestive in 16 of 51 abnormalities (31%). We conclude that endoscopy is required in the majority of hospitalized patients for the precise diagnosis of a congenital airway abnormality. Conventional dynamic radiographic studies are helpful to confirm a suspected diagnosis in patients with a strong clinical history and physical examination. When the diagnosis is not clear based on the patient presentation, endoscopy is more definitive than conventional dynamic radiography in identifying pediatric congenital airway abnormalities.

Congenital airway abnormalities requiring tracheotomy: a profile of 56 patients and their diagnoses over a 9 year period.

We reviewed the 9 year experience at the Children's Hospital of Philadelphia with patients requiring tracheotomy for a diagnosis of congenital airway abnormalities. Of the 56 patients, 28 (50%) had cardiovascular, or chromosomal abnormalities, neurologic conditions, or congenital syndromes, 24 (43%) were born prematurely, and 13 (23%) were found to have gastroesophageal reflux. Only 18 (32%) went on to eventual decannulation of their tracheotomy with a mean tracheotomy duration of 1.75 years. The majority of patients (75%) had multiple presenting signs. Stridor was the most common (54%), followed by accessory respiratory effort (39%), cyanosis (30%), apnea (29%), and failure to thrive (23%). Twenty eight patients (50%) had multiple airway abnormalities contributing to their need of a tracheotomy for airway protection orr ventilator dependence. Laryngeal abnormalities were found in 71% of patients, tracheal abnormalities in 48% of patients, bronchial abnormalities in 11%, and upper airway obstruction in 14%. Of the laryngeal abnormalities, laryngomalacia was the most common, followed by subglottic stenosis, glottic web, and vocal cord paralysis. Tracheomalacia was the most common tracheal abnormality. The relatively large percentage of patients with cardiovascular or other major malformations, and prematurity, accounts for comorbid factors in the need for prolonged tracheotomy (and low early decannulation rate). Although gastroesophageal reflux was found in a recognizable portion off the patients, it is unclear whether this represents a comorbid condition.

Complications of frontal sinusitis in adolescents: case presentations and treatment options.

Frontal sinusitis in adolescents can be a serious condition because of the severity of potential complications and rapid progression of disease. These complications may arise as a result of extension of the infection intracranially, to the frontal bone, and to the orbit. Infection may spread hematogenously or by direct extension. A series of seven adolescent patients with complications of frontal sinusitis is presented. Surgical options are necessitated by the location and extent of infection and include trephination, frontal sinus obliteration, and craniotomy. Recent advances in endoscopic sinus surgery have provided surgeons another access to the frontal recess. However, a combined otolaryngological/neurosurgical approach is essential for patients with intracranial complications.

Metastatic follicular thyroid carcinoma to the paranasal sinuses: a case report and review.

Thyroid carcinoma metastatic to the paranasal sinuses is extremely rare, with only 11 cases reported in the English and European literature. We report a case of metastatic follicular thyroid carcinoma to the clivus with extension into the sphenoid and posterior ethmoid sinuses. Pathological diagnosis was obtained using an intranasal endoscopic biopsy. As with our patient, metastatic thyroid carcinoma may present with symptoms related to distant metastases rather than the primary lesion. Distant metastases in differentiated thyroid carcinoma portends a poor prognosis. Our case of metastatic thyroid carcinoma to the paranasal sinuses is summarized in the context of the 11 additional cases, and treatment options are discussed.

Steady-state point-source stimulation of a nerve containing axons with an arbitrary distribution of diameters.

The paper extends a mathematical model for point-source electrical stimulation of a nerve. In the original model, it was assumed that all the axons in the nerve have the same diameter. In this paper the model is extended to represent a nerve with an arbitrary distribution of axon diameters. It is shown that the assumption of identical axons is justified for a typical human nerve if the 'representative' axon diameter is taken as the area-weighted average of the diameter distribution.

Transmural surgical gown pressure measurements in the operating theater.

Transmural gown pressures encountered when the surgeon comes into contact with a patient were measured in the operating theater. The surgical gown industry has assumed these pressures to be less than 5 psi in testing the efficacy of the gown and drape barrier material to impede bacterial transmission through its pores. In this study, pressure-sensitive contact film and resistive strain gauge recordings made from the surgeon's abdominal region and forearms indicated peak contact pressures in excess of 60 psi. This report indicates a need to reassess the basis of test utilization in evaluating barrier materials used in gowns and drapes.

Analysis of excitable cell activation: relative effects of external electrical stimuli.

In the functional electrical stimulation of nerve an expression defined as the 'activating function' has been introduced to evaluate the propensity for a particular fibre to excite. This approach to determine resulting activation is only an approximation as it neglects the presence of the fibres on the applied field, in contrast to activity determined from a rigorous solution to the core conductor/excitable membrane equations. An alternative approach to determining relative excitability based on the induced transmembrane potential is presented, thereby allowing for current redistribution via the space constant of the target fibre. The paper critically examines the approximations made with activating functions, and concludes that as currently formulated the activating function has limitations in predicting relative excitability under a number of important conditions. In contrast, it is the induced (passive) transmembrane potential that provides a quantitatively reliable estimate of the tendency for fibres to excite.

Point source nerve bundle stimulation: effects of fiber diameter and depth on simulated excitation.

Excitation response of different diameter myelinated nerve fibers situated at various depths within a cylindrical nerve bundle from the applied field of a point source electrode are analytically evaluated. For the potential field calculation, the fiber bundle is considered to be immersed in an infinite isotropic conductive medium and is idealized as an infinitely extending cylinder represented as an anisotropic bidomain (where electrical coupling from interstitial to intracellular space is included). Myelinated nerve fiber excitation is determined from a core-conductor nerve model, whose nodal currents are described by the Frankenhaeuser-Huxley kinetics and the aforementioned field providing the applied potentials. Stimulation level necessary for a nerve fiber to reach threshold is quantified in response to four descriptions of the volume conductor: the isotropic homogeneous case, the monodomain case, the bidomain case, and the "modified monodomain" case (where axial current is considered to flow through a parallel combination of longitudinal interstitial and intracellular resistive pathways, i.e., "complete" current redistribution). Model results indicate the importance of a bidomain representation of the nerve bundle, and provide insight into the relationship between the physical medium and the physiological properties of nerve fiber excitation.

Analysis of the longitudinal and radial resistivity measurements of the nerve trunk.

Of the many models of peripheral nerve in the literature, essentially all have relied on experimentally derived values for the anisotropic resistivity of the nerve bundle interstitial space. This paper is a comprehensive mathematical analysis of the most referenced experiment for the longitudinal and radial resistivity measurements of the nerve trunk, namely that of Tasaki. For the analysis of the longitudinal measurements we introduce intracellular as well as interstitial current pathways (not considered by Tasaki). For the radial measurement the resistivity is expected to depend on the geometric packing of fibers within the trunk. Since Tasaki's paper did not include a histological examination of the nerve trunk these measurements are difficult to evaluate. However, our analysis indicates the importance of including the above factors, in addition to the epineurial (and perineurial) sheath as a resistive pathway. Our mathematical analysis supports the experimental measurements and confirms an assumed nerve trunk composition with theoretically derived values for the interstitial resistivities. It is therefore concluded that, at present, an appropriate procedure in determining resistivity values for use in modeling is to derive these values for an idealized nerve bundle based on the microscopic (electrolytic) resistivity of the interstitial medium.