The Effect of Antioxidant Agents on Cisplatin-Induced Laryngeal Histological Alterations in Rats.

The larynx-related adverse effects that depend on cisplatin decrease patient comfort and many antioxidants have been used to eliminate these side effects. We aimed to identify the laryngeal mucosal changes imposed by cisplatin and investigated whether antioxidants, and their healing effects on these changes, may help reduce laryngeal complications in patients resulting from adverse effects in the larynx. A rat model was designed to evaluate the effects of cisplatin on the larynx and the protective role of antioxidants. Single-dose cisplatin was given both intraperitoneally alone and additionally administered with p-coumaric acid, melatonin, resveratrol, vitamin D, and oleic acid over 5 days. Whole larynges were dissected and evaluated histologically, histochemically, and immunohistochemically. Varying degrees of mucosal changes cisplatin group, but neither erosion nor an ulcer was observed. Numerous variable histological effects of antioxidants were observed on cisplatin exposed laryngeal mucosa. The most obvious effects of cisplatin were edema. The results of the study showed that resveratrol was the most preventive antioxidant agent against cisplatin-dependent mucosal changes. The highest increase in the Ki67 index was in the oleic acid group. Vitamin D increased stromal cyclooxygenase-2 expression that may have an effect on increasing mucosal damage.

Effect of Urban Particulate Matter on Vocal Fold Fibrosis through the MAPK/NF-κB Signaling Pathway.

Particulate matter (PM) is an environmental exposure factor that adversely affects human health. PM is a risk factor for various diseases. However, the mechanism by which PM affects the vocal folds (VF) has not yet been evaluated. Thus, we investigated the cytotoxic effects of PM on human vocal fold fibroblasts (hVFF) and the underlying signaling pathways. hVFF were isolated from human VF. The effect of PM on hVFF, and the underlying mechanism, were analyzed using Western blot, quantitative real-time polymerase chain reaction, and flow cytometry. In addition, a histological evaluation was performed in animal experiments. Cell proliferation decreased after the PM treatment. PM increased the expression of interleukin (IL)-6 and IL-1ß. The generation of reactive oxygen species (ROS) in PM-treated hVFF and subsequent activation of the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways were confirmed. Furthermore, PM increased the expression of fibrosis-related markers and induced the accumulation of collagen in the extracellular matrix. As a result, PM exposure significantly enhances the inflammatory response on VF through the ROS-mediated activation of the MAPK and NF-κB signaling pathways. In addition, PM promotes differentiation into myofibroblasts and induces fibrosis. These results suggest that PM triggers an inflammatory reaction through ROS production and causes VF fibrosis.

Risperidone-Induced Acute Laryngeal Dystonia: A Case Report.

BACKGROUND Antipsychotic medications are associated with multiple adverse effects, including metabolic syndrome, prolonged QT interval, and extrapyramidal symptoms. Acute laryngeal dystonia (ALD) is a rare and lethal form of extrapyramidal reaction. CASE REPORT A 27-year-old woman with schizophrenia on risperidone presented to our Emergency Department with a sensation of choking and respiratory distress, mimicking a panic attack. She developed a generalized dystonic reaction in the hospital, leading to diagnosis risperidone-associated ALD as a cause of her initial problems. She was discharged with an emphasis on being compliant with anticholinergic medication. However, her persistent respiratory symptoms prompted us to revisit the management plan. Her risperidone dose was tapered down to discontinue and an alternate drug was chosen. CONCLUSIONS ALD must be considered as a differential diagnosis when patients on antipsychotic medications present with respiratory distress. Our case highlights the association of ALD with an atypical antipsychotic agent, risperidone. Prompt recognition of this entity is necessary to prevent complications and guide definitive management.

Establishment and Analysis of False Vocal Folds Hypertrophy Model in Excised Canine Larynges.

OBJECTIVE: This study aimed to investigate the role of false vocal folds (FVFs) medialization in phonation and the acoustic impact of ventricular hypertrophy by establishing an FVF hypertrophy model. STUDY DESIGN: A prospective in vitro experiment was carried out. SETTING: The study was carried out using a pseudolung platform with high-speed camera in a soundproof room. MATERIALS AND METHODS: Control, degree I, and degree II FVFs hypertrophy were simulated in 10 excised larynges via fructose injection of 0.1 mL for degree I and 0.25 mL for degree II. Mean flow rate (MFR), fundamental frequencies (F0), formants, and sound pressure level were measured with a subglottal pressure of 1.5 kPa and 2.5 kPa, respectively. RESULTS: When the subglottal pressure was controlled at both at 1.5 kPa and at 2.5 kPa, the degree of FVF hypertrophy significantly influenced the distribution of the formants, F0, and MFR in excised canine larynges. Increasing the degree of hypertrophy was associated with a decrease in F0 and an increase in MFR. In degree II FVF hypertrophy models, the sound pressure level and the first formant were significantly higher (P < 0.05) than in normal models. CONCLUSION: Hypertrophy of the FVFs has a significant influence on the distribution of sound energy and is associated with changes in sound quality.

Development of an inhalation reference concentration for diethanolamine.

An inhalation reference concentration (RfC) was developed for diethanolamine (DEA), based principally on evaluation of three animal studies (Gamer et al., 1993, 1996, 2008). The RfC (25 µg/m3) was based on statistically significantly increased relative liver weight in female rats in Gamer et al. (2008) as the critical effect. The lower confidence limit on the benchmark dose (BMDL10 of 5.5 mg/m3) was adjusted to a human equivalent concentration and to continuous exposure before dividing the final point of departure (2.3 mg/m3) by a total factor of 90 that considered standard key areas of uncertainty (intrahuman variability, potential interspecies toxicodynamic differences, database limitations). While laryngeal effects observed in Gamer et al. (2008) were also considered as candidate critical effects, evaluation of the adversity and human relevance of rat laryngeal squamous metaplasia and concomitant effects at the various exposure levels resulted in identifying a LOAEL for laryngeal squamous hyperplasia and chronic inflammation that was much higher than the liver weight LOAEL identified. The RfC of 25 µg/m3 is considered health protective for the general population and can be used to evaluate the potential health effects of long-term environmental exposure of the general public (i.e., long-term, ambient air dispersion modelling or monitoring data).

Sudden Death by Spontaneous Epiglottic Hematoma Secondary to High Blood Levels of Warfarin.

A 67-year-old man was found dead, at his home. On external examination, we found a voluminous purplish black ecchymosis of the anterior neck area. On internal examination, we found a voluminous epiglottis hematoma completely obstructing the upper airway. It was associated with other sites of intra-abdominal hemorrhage. Toxicological studies revealed the presence of warfarin at a concentration of 8.4 mg/L in peripheral blood, which supposes an INR well above 4.5. To conclude, we supposed death was due to asphyxia secondary to a spontaneous epiglottic hematoma caused by a high blood concentration of warfarin. Hemorrhage in the epiglottis is very rare. To our knowledge, our patient is the only case of "sudden death" reported with spontaneous epiglottic hematoma due to high blood concentration of warfarin. In forensic practice, an anterior neck ecchymosis, without trauma, may suggest hemorrhage into soft airway tissues. Pathology findings make it possible to exclude exogenous trauma.

Pharyngolaryngeal ulcers associated with the improper use of alendronate.

Bisphosphonates can cause mucosal irritation. Although esophageal ulceration is a well-recognized adverse effect of bisphosphonates, pharyngolaryngeal ulcers associated with the improper use of oral bisphosphonates have rarely been described. A previously healthy 78-year-old woman presented with refractory pharyngolaryngeal ulcers. Extensive evaluation, including biopsy, bacterial culture, and blood tests did not identify any findings that indicated a specific disease diagnosis. Antibiotics and oral prednisolone were ineffective. Ultimately, it was found that the patient regularly took a tablet of alendronate, a type of bisphosphonate, by dissolving it in the oral cavity. Within 2 weeks after withdrawal of the use of the medication, her symptoms were eliminated, and the lesions were completely healed. This case illustrates the importance of correct administration of bisphosphonates. Given the widespread use of bisphosphonates, physicians need to be aware that their improper use can cause pharyngolaryngeal ulcers.

Dementia with Lewy bodies presenting marked tongue protrusion and bite due to lingual dystonia: A case report.

We report the patient of a 53-year-old woman who developed subacute-onset marked tonge protrusion and bite. She was diagnosed as dementia with Lewy bodies (DLB) from the clinical features including progressive cognitive decline, visual hallucinations, parkinsonism, and severe insomnia and depression, and the radiological finding of low dopamine transported uptake in basal ganglia by Dat SCAN and low blood circulation in occipital lobe of cerebrum. The patient received 600 mg doses of levodopa for over a year, followed by rotigotine and ropinirole with a rapid increase of dosage. It is believed that these treatments stimulated and sensitized dopamine D1 receptors, thereby inducing lingual dystonia. Furthermore, the patient demonstrated dyspnea and attacks of apnea caused by the closure of bilateral vocal cords due to laryngeal dyskinesia. After initiation of the neuroleptic, olanzapine, for a short duration, the high dose of levodopa overlapped with neuroleptic sensitivity, suggesting DOPA-induced dystonia and dyskinesia. This interaction can sometimes lead to lethal adverse events, and must be considered very important when treating patients with DLB.

Effect of available intravenous access on accuracy and timeliness of epinephrine administration.

PURPOSE: To evaluate the effect of available intravenous (IV) access on the accuracy and timeliness of epinephrine administration during a surprise mock severe contrast reaction. METHODS: Informed consent was waived for this prospective randomized IRB-approved study. Radiology trainees with previous annual hands-on contrast reaction training (n = 46) were randomized to one of two surprise mock contrast reactions over a 23-month period: Group 1-severe laryngeal edema with IV access present (n = 27) or Group 2-severe laryngeal edema without IV access present (n = 19). Both intramuscular (IM, Epi-Pen(®)) and IV epinephrine were available in both scenarios. Time-to-treat and epinephrine administration error rates were compared by study group and by route of administration using two-tailed Student's t test or χ (2) test. Epinephrine administration errors were correlated with training experience using Pearson's correlation. RESULTS: Mean time to epinephrine administration was significantly faster for scenarios without IV access (Group 2: 35 ± 16 s vs. Group 1: 62 ± 49 s, p = 0.03), and for intramuscular administrations overall (IM: 42 ± 34 s vs. IV: 98 ± 46 s, p < 0.001). Epinephrine administration errors were common: (63% [17/27, Group 1] vs. 61% [11/18, Group 2], p = 1.00), had no relationship with time to most recent hands-on training (r = 0.24, p = 0.11), and were not predicted by year of post-graduate training (r = 0.04, p = 0.79). CONCLUSIONS: Lack of IV access is associated with a faster epinephrine administration time but no improvement in epinephrine administration error rate among radiology trainees responding to a surprise mock severe contrast reaction. Annual hands-on training appears to have little effect on epinephrine administration accuracy.

Fatal laryngeal angioedema: a case report and a workup of angioedema in a forensic setting.

Angioedema is an episodic swelling of the deep dermis, subcutis, and/or submucosal tissue due to an increase in local vascular permeability. Swelling may involve skin, respiratory, and gastrointestinal tracts. The most commonly involved areas are the periorbital region and the lips. Here we report a case of a fatal laryngeal obstruction due to angioedema likely caused by an angiotensin-converting-enzyme inhibitor. The decedent, a 58-year-old man, was witnessed developing sudden facial swelling and acute respiratory difficulties quickly followed by unresponsiveness. His past medical history suggested that this was his second episode of angioedema without urticaria. Postmortem examination revealed a complete laryngeal obstruction in the absence of infection, neoplasm, or autoimmune disease. Postmortem computed tomography of the head and neck showed a complete obstruction of the upper airway. Based on the current understanding of the pathophysiology of different types of angioedema, we will suggest a workup of angioedema without urticaria in the forensic setting and offer readers resources they can use in their practice.