Gender and laterality in semicircular canal dehiscence syndrome.

OBJECTIVE: To determine if there is gender or laterality predilection in patients with semicircular canal dehiscence syndrome. METHODS: A multi-institutional chart review was performed to identify patients diagnosed with semicircular canal dehiscence between 2000 and 2015. A systematic literature search was conducted using PubMed to further identify patients with semicircular canal dehiscence. Age, gender and laterality data were collected. Statistical analysis was performed to evaluate for gender or laterality preponderance. RESULTS: A total of 682 patients with semicircular canal dehiscence were identified by literature and chart review. Mean age of diagnosis was 49.75 years (standard deviation = 15.33). Semicircular canal dehiscence was associated with a statistically significant female predominance (chi-square = 7.185, p = 0.007); the female-to-male ratio was 1.2 to 1. Left-sided semicircular canal dehiscence was most common, followed by right-sided then bilateral (chi-square = 23.457, p < 0.001). CONCLUSION: Semicircular canal dehiscence syndrome is most commonly left-sided and exhibits a female predominance. This may be secondary to morphological cerebral hemisphere asymmetries in both sexes and a predilection of women to seek more medical care than men.

Survival of the 8.5 mm osseointegrated abutment, and its utility in the obese patient.

BACKGROUND: Most of the literature regarding osseointegrated implantation for hearing rehabilitation focuses on the 5.5 mm abutment. This study aimed to add to the data available on the survival of the 8.5 mm abutment, and to describe its utility in obese patients. OBJECTIVE: To review the outcomes of patients who received a bone-anchored hearing aid implant, and create a model comparing the mechanical forces acting upon combinations of fixture and abutment lengths. METHODS: Retrospective chart review and mathematical modelling. RESULTS: In this retrospective cohort study comprising 25 patients, less abutment overgrowth was observed in the 8.5 mm abutment recipients versus recipients of the 5.5 mm abutment. When the principle of equilibrium of a rigid body was applied, the 8.5 mm abutment was at a calculated mechanical disadvantage compared with the 5.5 mm abutment. CONCLUSION: The 8.5 mm abutment may be useful in patients with copious subcutaneous soft tissue as in the obese population. The 8.5 mm abutment has a calculated mechanical disadvantage, potentially putting the implant under greater mechanical stress; however, the clinical relevance of this is unclear.

Noise exposure in convertible automobiles.

OBJECTIVE: To quantify the noise exposure received while driving a convertible automobile with the top open, compared with the top closed. METHODS: Five different convertible automobiles were driven, with the top both closed and open, and noise levels measured. The cars were tested at speeds of 88.5, 104.6 and 120.7 km/h. RESULTS: When driving with the convertible top open, the mean noise exposure ranged from 85.3 dB at 88.5 km/h to 89.9 dB at 120.7 km/h. At the tested speeds, noise exposure increased by an average of 12.4-14.6 dB after opening the convertible top. CONCLUSION: Driving convertible automobiles at speeds exceeding 88.5 km/h, with the top open, may result in noise exposure levels exceeding recommended limits, especially when driving with the convertible top open for prolonged periods.

Negative association between treated osteoporosis and benign paroxysmal positional vertigo in women.

OBJECTIVE: To determine the degree of association, if any, between benign paroxysmal positional vertigo and osteoporosis, both of which are disorders of impaired calcium carbonate homeostasis. METHODS: A retrospective chart review was undertaken in two otology clinics to assess the prevalence of treated osteoporosis in 260 women with and without benign paroxysmal positional vertigo, between the ages of 51 and 80 years. RESULTS: There was a statistically significant, negative association between benign paroxysmal positional vertigo and treated osteoporosis in women aged 51 to 60 years. We also observed a trend towards a negative association for women in their 60s, and for the group as a whole. CONCLUSION: Osteoporosis, or the medication used to treat it, may provide protection against benign paroxysmal positional vertigo.

Effect of tamoxifen on transforming growth factor beta1 production by keloid and fetal fibroblasts.

BACKGROUND: Evidence suggests that keloid scar formation may be mediated, in part, by deranged growth factor activity, including that of transforming growth factor (TGF) beta1. Tamoxifen citrate has shown promise in the treatment of keloids. OBJECTIVE: To evaluate the effect of tamoxifen on autocrine growth factor expression in keloid and fetal dermal fibroblasts, which exhibit scar-free healing. DESIGN: Serum-free cell lines of keloid and fetal dermal fibroblasts were established. Cell cultures were exposed to different concentrations of tamoxifen solution (8 and 12 or 16 micromol/L). Cell counts were performed and supernatants collected at 24, 48, and 96 hours. Cell-free supernatants were quantitatively assayed for TGF-beta1 expression. RESULTS: Keloid fibroblasts show increased per-cell TGF-beta1 production compared with fetal fibroblasts. Tamoxifen appeared to decrease per-cell TGF-beta1 production at each of the time points evaluated. CONCLUSIONS: Keloids likely arise due to locally insufficient or excessive concentrations of specific growth factors. The higher level of TGF-beta1 produced by keloid cells compared with fetal fibroblasts could be related to the aberrant wound healing seen with keloids. The addition of tamoxifen may lead to improved wound healing in keloids by decreasing the expression of TGF-beta1.

Head and neck cancer in cardiothoracic transplant recipients.

INTRODUCTION: There is an increased incidence of cancer in patients after organ transplantation. We reviewed a large series of cardiothoracic transplant recipients to determine the incidence and natural history of head and neck malignancy. METHODS: A total of 1069 heart (n = 855), heart/lung (n = 111), and lung (n = 103) transplants were performed at Stanford University from January 1968 to February 1998. Demographic data, risk factors, and disease course were evaluated in patients who developed cancer. The mean length of follow-up was 8.9+/-5.2 years. RESULTS: One hundred twenty patients (11.2%) developed 547 non-lymphomatous malignancies. The mean number of malignancies per cancer patient was 4.6. The average time from transplantation to development of cancer was 63.1 months. A total of 50.5% of malignancies presented in the head and neck; 96.4% of these were cutaneous in origin and 3.6% were noncutaneous. Of cutaneous malignancies, 79.3% were squamous cell carcinoma and 15.9% were basal cell carcinoma Cutaneous malignancies most commonly presented on the scalp, cheek, lip, and neck. Noncutaneous malignancies involved the oral cavity (5), thyroid (4), and parotid (1). Thirteen percent of cutaneous head and neck cancers behaved aggressively, requiring extensive management including radical surgery, radiation, and/or chemotherapy. A total of 34.2% of cancer patients developed metastases and 54.9% of cancer patients died as a direct result of cancer. A total of 68% of cancer patients were smokers and 23.8% had significant alcohol use. CONCLUSION: Transplant recipients have an increased incidence of cancer presenting in the head and neck. Malignancies in transplant patients behave more aggressively than in the general population. Recognition of this aggressive biological behavior and heightened cancer surveillance should result in improved outcomes.

Halothane depresses action potential conduction in hippocampal axons.

General anesthetics are thought to depress the central nervous system (CNS) by acting at synapses; however, only a few studies have compared effects on axonal conduction with effects on synaptic responses using mammalian CNS preparations. The present study used glutamate receptor antagonists (CNQX/APV) or low calcium to block synaptic transmission, allowing Schaffer-collateral axon fiber volleys to be recorded from rat hippocampal brain slices. Since fiber volleys are compound action potentials, they provide a measure of axonal conduction in Schaffer-collateral fibers. Clinical concentrations of the inhalational anesthetic, halothane (1 rat MAC, 1.2 vol.%), produced an 18 +/- 2.3% depression of fiber volley amplitudes (mean +/- S.D.; p < 0.001 ANOVA, n = 10). Depression of action potential conduction accounted for approximately 30% of the overall depression of synaptic transmission produced by halothane at this concentration. Halothane-induced fiber volley depression occurred with little change in conduction velocity, similar to the effect seen with decreased stimulus intensity, but significantly different from the decreased velocity produced by tetrodotoxin (100 nM, p < 0.005). The results indicate that halothane can depress axonal conduction at clinically relevant concentrations and that this depression could contribute to the CNS depression that is associated with anesthesia.

Volatile anesthetics depress glutamate transmission via presynaptic actions.

BACKGROUND: Recent evidence for a presynaptic depression of glutamate release produced by volatile anesthetics prompted the current study of isoflurane and halothane effects on glutamate-mediated transmission in the mammalian central nervous system. METHODS: Electrophysiologic recordings from CA1 neurons in rat hippocampal brain slices were used to measure anesthetic effects on glutamate-mediated excitatory postsynaptic potential (EPSP) amplitudes and paired pulse facilitation. Paired pulse facilitation is known to be altered when the calcium-dependent release of glutamate is depressed, but not when EPSP amplitudes are depressed by postsynaptic mechanisms. RESULTS: Isoflurane depressed EPSP amplitudes over a concentration range of 0.35-2.8 vol %, with a 50% depression (EC50) occurring at 1.0 vol % (0.71 rat minimum alveolar concentration). This depression was accompanied by an increase in paired-pulse facilitation of approximately 30% at 1.7 vol %, using interpulse intervals of 120 ms. Halothane depressed EPSP amplitudes in a concentration-dependent manner (0.3-2.4 vol %, EC50 = 1.1 minimum alveolar concentration; 1.3 vol %) and also increased facilitation by approximately 20% at 1.2 vol %. These effects persisted in the presence of 10 microM bicuculline, indicating that enhanced gamma-aminobutyric acid-mediated inhibition was not involved. The anesthetic-induced increase in facilitation and EPSP depression was mimicked by lowering extracellular calcium, which is known to depress glutamate release at these synapses. The postsynaptic glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione depressed EPSP amplitudes with no change in facilitation. CONCLUSIONS: Our results confirm earlier findings that clinically relevant concentrations of volatile anesthetics depress glutamate-mediated synaptic transmission. The observed increases in synaptic facilitation support recent findings from biochemical and electrophysiologic studies indicating presynaptic sites of action contribute to anesthetic-induced depression of excitatory transmission. This anesthetic-induced reduction in glutamate release would contribute to the central nervous system depression associated with anesthesia by adding to postsynaptic depressant actions on glutamate receptors.

Riluzole anesthesia: use-dependent block of presynaptic glutamate fibers.

BACKGROUND: Riluzole (RP 54274) is an experimental benzothiazole with anesthetic properties, but little is known about its synaptic or cellular actions. METHODS: The authors investigated riluzole effects on synaptic response of CA 1 pyramidal neurons in rat hippocampal brain slices. Electrophysiologic recordings of population spikes (PS), excitatory postsynaptic potentials (EPSP), and fiber volleys were studied. Paired pulse stimulation (120 ms interpulse interval) was used to measure effects on gamma-amino butyric acid (GABA)-mediated synaptic inhibition, and stimulus trains (33 Hz) were used to test for use-dependent effects. RESULTS: Synaptically evoked PS discharge was blocked in a concentration-dependent manner by riluzole (2.0-20 microM), similar to effects produced by other anesthetics. Paired pulse inhibition was not altered by riluzole. In contrast, 20 microM thiopental produced a marked increase in paired pulse inhibition. Riluzole (5.0 microM) produced a 46.6 +/- 19.8% depression of glutamate-mediated EPSPs, which could account for most of the mate-mediated EPSPs, which could account for most of the depression of PS discharge (54.2 +/- 12.6%) produced by this concentration. Riluzole produced a 36 +/- 17% depression of fiver volley amplitudes, which, based on input/output analysis, could completely account for the depression of EPSPs. The depression of fiber volley amplitudes showed a marked use-dependence; the second and subsequent action potentials in a train were progressively depressed by riluzole to a greater extent than the first action potential. CONCLUSIONS: Riluzole produced a potent block of excitatory synaptic transmission via depression of presynaptic conduction in glutamatergic nerve fibers. The use-dependent depression observed resembled that produced by some local anesthetics on nerve conduction and sodium channels. The presynaptic action, together with a lack of effect on gamma-amino butyric acid-mediated inhibition, provides a unique mechanism of action for a general anesthetic.

CGRP increases the rate of corneal re-epithelialization in an in vitro whole mount preparation.

A number of studies have localized CGRP to nerves in the cornea and iris, and it is thought that CGRP, along with other neuropeptides, is involved in pain sensation. It is also possible that CGRP could mediate trophic influences between nerve endings and corneal epithelium. This investigation utilized an in vitro rabbit corneal whole mount preparation to study the effect of topical 2.5 microM CGRP application on epithelial wound healing rates of 5 mm diameter epithelial wounds. CGRP (2.5 microM) was applied topically to 5 mm epithelial wounds at 0, 4, 16, 20, 24, 28, 40, 44, 48, 52, 56, 64, 68, and 72 hours after wounding and healing was visualized with fluorescein. CGRP was found to increase the epithelial wound healing rate by 25%, from 51 +/- 3 microns/hr for the control corneas, to 64 +/- 2 microns/hr for CGRP-treated corneas (mean +/- standard error, n = 10). Histological examination of the corneas following healing showed that the epithelium of the CGRP-treated corneas healed in a similar manner as in the control corneas. These findings may have clinical utility for the understanding and treatment of corneal and other epithelial wounds.

Diltiazem spares corneal A delta mechano and C fiber cold receptors and preserves epithelial wound healing.

Recent interest in the corneal analgesic properties of diltiazem prompted the present study examining concentration-dependent effects of this calcium channel blocker on C fiber cold receptors and A delta mechanoreceptors. Both afferent fiber types mediate an eye blink reflex, important for protecting the corneal surface. The effects of neuroactive concentrations of diltiazem on corneal would healing were also studied. An in vitro rabbit cornea preparation was used for both electrophysiological recording and wound healing, allowing precise concentration-response analysis. Diltiazem produced a concentration-dependent depression of cold fiber discharge activity (10 to 250 microM), but did not affect mechanoreceptor afferents. In addition, the broad spectrum Ca2+ channel blockers, Ni2+ and Cd2+, did not cause a significant reduction in A delta mechano or C fiber discharge activity. Diltiazem had no effect on corneal epithelial wound healing to a concentration of 50 microM. This is important if diltiazem is to be used for therapeutic control of pain following corneal injury or surgery, because sparing of the eye blink reflexes and wound healing are desirable properties for a corneal analgesic.