Fibrin with Laminin-Nidogen Reduces Fibrosis and Improves Soft Palate Regeneration Following Palatal Injury.

This study aimed to analyze the effects of fibrin constructs enhanced with laminin-nidogen, implanted in the wounded rat soft palate. Fibrin constructs with and without laminin-nidogen were implanted in 1 mm excisional wounds in the soft palate of 9-week-old rats and compared with the wounded soft palate without implantation. Collagen deposition and myofiber formation were analyzed at days 3, 7, 28 and 56 after wounding by histochemistry. In addition, immune staining was performed for a-smooth muscle actin (a-SMA), myosin heavy chain (MyHC) and paired homeobox protein 7 (Pax7). At day 56, collagen areas were smaller in both implant groups (31.25 ± 7.73% fibrin only and 21.11 ± 6.06% fibrin with laminin-nidogen)) compared to the empty wounds (38.25 ± 8.89%, p < 0.05). Moreover, the collagen area in the fibrin with laminin-nidogen group was smaller than in the fibrin only group (p ˂ 0.05). The areas of myofiber formation in the fibrin only group (31.77 ± 10.81%) and fibrin with laminin-nidogen group (43.13 ± 10.39%) were larger than in the empty wounds (28.10 ± 11.68%, p ˂ 0.05). Fibrin-based constructs with laminin-nidogen reduce fibrosis and improve muscle regeneration in the wounded soft palate. This is a promising strategy to enhance cleft soft palate repair and other severe muscle injuries.

Muscle fibrosis in the soft palate: Delivery of cells, growth factors and anti-fibrotics.

The healing of skeletal muscle injuries after major trauma or surgical reconstruction is often complicated by the development of fibrosis leading to impaired function. Research in the field of muscle regeneration is mainly focused on the restoration of muscle mass while far less attention is paid to the prevention of fibrosis. In this review, we take as an example the reconstruction of the muscles in the soft palate of cleft palate patients. After surgical closure of the soft palate, muscle function during speech is often impaired by a shortage of muscle tissue as well as the development of fibrosis. We will give a short overview of the most common approaches to generate muscle mass and then focus on strategies to prevent fibrosis. These include anti-fibrotic strategies that have been developed for muscle and other organs by the delivery of small molecules, decorin and miRNAs. Anti-fibrotic compounds should be delivered in aligned constructs in order to obtain the organized architecture of muscle tissue. The available techniques for the preparation of aligned muscle constructs will be discussed. The combination of approaches to generate muscle mass with anti-fibrotic components in an aligned muscle construct may greatly improve the functional outcome of regenerative therapies for muscle injuries.

Species generalization and differences in Hedgehog pathway regulation of fungiform and circumvallate papilla taste function and somatosensation demonstrated with sonidegib.

Species generalization in the profound, modality-specific effects of Hedgehog pathway inhibition (HPI) in taste organ homeostasis and sensation is shown. With the HPI, cancer drug sonidegib, we demonstrate that the rat taste system, in addition to mouse, is regulated by Hedgehog signaling. After sonidegib treatment for 16-36 days in rat, there is loss of taste buds (TB) in soft palate, in fungiform (FP) and circumvallate papillae (CV), and elimination of taste responses from chorda tympani and glossopharyngeal nerves. The retained innervation in FP and CV during HPI cannot sustain TB. Responses to tactile stimuli are not altered, and temperature responses are reduced only after 28 days treatment, demonstrating modality-specific effects. Rat FP and neural effects are similar to those in mouse whereas TB and neural response effects from the rat CV are much more severe. When recovery is introduced in mouse after prolonged, 48 days HPI, the TB in CV are restored whereas those in FP are not. Overall, Hedgehog signaling regulation is shown to generalize to the rat taste system, and the modality-specific controls in taste organ sensation are affirmed. The reported, debilitating taste disturbances in patients who use HPI drugs can be better understood based on these data.

Injections of Local Anesthetics into the Pharyngeal Region Reduce Trapezius Muscle Tenderness.

BACKGROUND: Neck pain is a frequent reason for seeking medical advice. Neuroanatomical findings suggest a close connection between the pharynx and the trapezius region. Irritation of the pharynx may induce tenderness of this area. Specific tender points, called neck reflex points (NRPs), can be identified here with high reproducibility. We hypothesized that therapeutic local anesthesia (TLA; or neural therapy, NT) in the pharyngeal region can reduce tenderness in patients with therapy-resistant neck pain. PATIENTS AND METHODS: 17 consecutive female patients with chronic cervical pain and positive trapezius NRPs received bilateral injections of 0.5 ml 1% procaine into the palatine velum. The NRPs were assessed using a 3-level pain index (PI = 0, 1, or 2) before and 3-5 min after each injection. RESULTS: We found a significant reduction in tenderness of the NRP of the trapezius region (NRP C7) immediately after TLA/NT. 30 positive NRPs were found before therapy and only 13 after therapy (p < 0.01). The average PI of the NRP C7 was 1.24 ± 0.77 before and 0.35 ± 0.59 after therapy (right side), and 1.34 ± 0.59 before and 0.59 ± 0.69 after therapy (left side). The pre- and post-therapy PI values were significantly different on both the right and left sides of the trapezius region (p < 0.01). No adverse effects were observed. CONCLUSIONS: Pharyngeal irritation may induce and maintain therapy-resistant cervical pain in patients with chronic pharyngeal disease. These patients could benefit from remote TLA/NT injections in the pharyngeal region.

An animal model of obstructive sleep apnoea-hypopnea syndrome corrected by mandibular advancement device.

OBJECTIVE: The aim of the study is to establish a stable animal model of obstructive sleep apnoea-hypopnea syndrome (OSAHS) and assess the effectiveness of a mandibular advancement device (MAD). MATERIALS AND METHODS: Eighteen 6-month-old male New Zealand white rabbits were randomized into three groups according to intervention: Group OSAHS, Group MAD, and a control group (n = 6 for each group). Rabbits in Group OSAHS and Group MAD were established as OSAHS model by injection, at a dose of 2 ml hydrophilic polyacrylamide gel, in the submucous muscular layer of the soft palate. Computed tomography (CT) and polysomnography (PSG) showed that OSAHS was developed successfully, the rabbits in Group MAD were fitted with the MAD and CT of the upper airway and PSG evaluated its effectiveness. Histological observation of the injection sites was conducted. RESULTS: CT scans showed the reduced sagittal space and cross-sectional areas of retropalatal upper airway in Group OSAHS were corrected by MAD (upper airway space in Group MAD was similar to that in the control group). The rabbits in Group OSAHS developed obvious sleep apnoea and hypopnea in supine position, with increased apnoea-hypopnea index and decreased oxygen saturation (SaO2). These were significantly improved by MAD and apnoea and hypopnea were not observed. Histology of the soft palate showed that the injected gel was entirely surrounded with connective tissues. CONCLUSION: We primarily developed an OSAHS and MAD therapy animal model with narrow oropharynx in upper airway which could be further available for OSAHS analysis.

Effects of a mandibular advancement device on genioglossus in obstructive sleep apnoea hypopnea syndrome.

OBJECTIVE: To investigate effects of mandibular advancement device (MAD) therapy for obstructive sleep apnoea hypopnea syndrome (OSAHS) on the genioglossus contractile properties and fibre-type distribution. MATERIALS AND METHODS: Thirty 6-month old male New Zealand white rabbits were randomised into three groups: OSAHS, MAD, and controls. Rabbits in Group OSAHS and Group MAD were established as OSAHS models by injection, at a dose of 2 ml hydrophilic polyacrylamide gel, via the submucous muscular layer of soft palate. Spiral computed tomography (CT) showed a significant reduced retropalatal upper airway, and apnoeas happened with an increase of Apnea Hypopnea Index (AHI) and a decrease of blood oxygen saturation during polysomnography (PSG), which indicated the OSAHS model developed successfully. OSAHS rabbits in Group MAD were fitted with a MAD made from self-curing composite resin, at 30 degrees to the upper incisors, and the mandible was guided forward 3 to 4mm. Further, spiral CT and PSG suggested MAD was effective. Rabbits in 3 groups were induced to sleep for 4-6 hours per day for 8 weeks, after which the genioglossus was removed, mounted in a tissue bath, and stimulated through platinum electrodes; maximal twitch tension, contraction time, half-relaxation time, force-frequency relationship, and fatigability were recorded. The percentage of Type I and Type II fibres was quantified. RESULTS: The fatigability and percentage of Type II fibres of genioglossus increased in Group OSAHS compared with controls; this abnormality was corrected by MAD. CONCLUSION: MAD therapy for OSAHS could prevent genioglossus fatigue and abnormal fibre-type distribution of genioglossus in OSAHS.

Necrosis of the intranasal structures and soft palate as a result of heroin snorting: a case series.

BACKGROUND: The link between nasal inhalation of cocaine and nasal and palatal necrosis is well documented. In contrast, few data are available concerning nasal mucosa necrosis related to heroin snorting. The authors report here the retrospective analysis of 24 cases of orofacial lesions in patients with nasal heroin usage, collected between 2006 and 2012. CASES: The cases concern 17 males and 7 females (median age 29.5 (range: 24-42)) with chronic consumption of intranasal heroin (from 2 months to more than 10 years). Six patients had a history of cocaine abuse. The median daily amount of heroin consumption was 5 g (range: 0.5-10). The complications were nasal perforation (11 cases), nasal ulceration or erythema (5 cases), nasal septum necrosis (5 cases), pharyngeal ulceration (3 cases), and palate damages (5 cases). The most common clinical signs and symptoms were nasal pain, purulent sputum, dysphagia, and rhinitis. Maintenance therapy with methadone (19 cases) or buprenorphine (3 cases) was initiated. In 8 cases, the injury improved. DISCUSSION: The potential of heroin to induce destructive orofacial lesions should be considered when nasal damages are observed in patients with drug abuse. A multidisciplinary approach seems to be the most effective means of managing such patients.

Pharyngeal chemosensitivity in patients with obstructive sleep apnea and healthy subjects.

Signs of pharyngeal neurodegeneration have been detected in patients with obstructive sleep apnea (OSA). Along with this neurodegeneration, a decreased pharyngeal sensitivity to mechanical stimulation has been described. The decreased sensitivity may play a role in the pathophysiology of this disease. The aim of the study was to investigate the chemosensitivity of the pharyngeal mucosa in patients with OSA compared with controls. Healthy controls and patients with OSA (age: 30-60 years) were included. Testing of oropharyngeal chemosensitivity was performed with subjective intensity ratings of capsaicin (SIR, visual analogue scale 0-10), air puffs (presented with an olfactometer), and stimulation with CO2 at the posterior pharyngeal wall. A 2-point discrimination test at the soft palate, an intensity rating of capsaicin at the tongue, and a nasal lateralization test were performed. Twenty-six patients with OSA and 18 healthy controls were included. No differences were detected in the SIR of capsaicin at the tongue or in the nasal lateralization test. At the pharynx, a decreased sensitivity to capsaicin (OSA: 6.8 ± 2.3; healthy control: 8.6 ± 1.3), air puffs (OSA: 2.8 ± 1.9; healthy control: 4.2 ± 1.6), and stimulation with CO2 (OSA: 1.5 ± 1.7; healthy control: 2.8 ± 1.8) were demonstrated in patients with OSA (all P < 0.05). Two-point discrimination at the soft palate was reduced with statistical significance in the OSA group (OSA: 11.5 ± 5.4 mm; healthy control: 5.0 ± 2.4 mm). The results suggest reduced pharyngeal chemosensitivity in OSA patients in addition to the reduced mechanical pharyngeal sensitivity shown with 2-point discrimination. This demonstrates peripheral neurodegeneration in the context of this disease.

Clinical assessment of disease severity in recurrent aphthous stomatitis.

BACKGROUND: Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosal diseases in many parts of the world. However, there is very limited published clinical evidence for the therapies used in this condition. This could be partly due to the difficulty in evaluating the efficacy of oral ulcer treatment objectively. In this paper, we present a method for assessing and monitoring the severity of oral ulcers before and after treatment. METHODS: Six ulcer characteristics, number, size, duration, ulcer-free period, site and pain, were used to generate an ulcer severity score (USS). The scores for 223 RAS patients were determined, and 79 were scored again after 3-month therapy with topical betamethasone. RESULTS: The scores for the minor RAS group were between 18 and 43 (mean 29.2 ± 5.3). The mean score in the major ulcers group (range: 28-60, mean 39.9 ± 6.1) was significantly greater than in the minor group (P < 0.001). The herpetiform recurrent ulcers score range was wide (range: 18-57, mean 36.6 ± 8.4). The mean severity score decreased significantly after treatment (P < 0.001). CONCLUSIONS: The USS was indicative of the disease activity in recurrent oral ulceration. It helped in assessing the efficacy of therapy, as the change in the numerical score reflected the change in ulcer severity in response to treatment. This tool may well prove to be of value in clinical management, research and in clinical trials.

Clonazepam in the treatment of essential palatal tremors.

Essential Palatal tremor (EPT) is a rare disorder presenting as unilateral or bilateral rhythmic involuntary movements of the soft palate. There is mention of the utility of benzodiazepines like clonazepam probably because of their gamma amino butyric acid (GABA) agonistic property. But no reports are available for the same. Here we report a 30-year old married female patient who presented with the complaints of pain in the lower part of face, behind the ears, back side of neck and clicking sound in her. General physical examination (GPE) revealed symmetrical rhythmic flapping movements of the soft palate and the uvula. Central nervous system (CNS) examination did not reveal any focal deficits and Magnetic resonance imaging (MRI) of the brain was normal. She was diagnosed as having EPT and treated successfully with clonazepam.

Palatal sclerotherapy for the treatment of intermittent dorsal displacement of the soft palate in 51 standardbred racehorses.

This retrospective study evaluated the efficacy and side effects of palatal sclerotherapy in standardbred racehorses suspected to have intermittent dorsal displacement of the soft palate (IDDSP). Fifty-one horses were treated with multiple endoscopically guided injections of 3% sodium tetradecyl sulfate in the soft palate. Two groups were identified: those that had respiratory noises during exercise (n = 27) and those that did not (n = 24). Treatment was well-tolerated. Furthermore, horses significantly reduced their racing times for the last 400 m compared with their times before treatment and even when their times were compared to the mean times for horses in the same race. In conclusion, palatal sclerotherapy appears to be a suitable alternative therapeutic option for horses suspected to have IDDSP.

Histological and biomechanical effects of palatal sclerotherapy in the horse using sodium tetradecyl sulfate.

Palatal sclerotherapy using sodium tetradecyl sulfate has been suggested as a treatment for dorsal displacement of the soft palate in young Standardbred horses. The present study evaluated histological and biomechanical changes in the equine soft palate following trans-endoscopic treatment with a low dose of this compound. Two horses were euthanased and examined at 2 weeks and at 1, 2, 4 and 6 months post-sclerotherapy, while two further horses served as untreated controls. The technique was easily performed in all cases without major complications. On histological examination there was no evidence of palatal necrosis, inflammation or fibrosis in any of the treated or control animals. There was no variation in the density of palatal connective tissue between individuals, and on biomechanical assessment no significant difference in the stiffness of the palatal tissue was found between treated and control horses at any time. The lower dose of sodium tetradecyl sulfate used in this study relative to previous reports, might explain the absence of tissue alterations. This method of sclerotherapy did not alter the morphology or biomechanical properties of normal equine soft palates.

Palatal sclerotherapy: a potentially useful treatment of intermittent dorsal displacement of the soft palate in juvenile standardbred racehorses.

This study was aimed at evaluating the tolerability and the efficacy of palatal sclerotherapy in juvenile standardbred racehorses with easily audible "snoring-like" respiratory noises suspected to be the result of intermittent dorsal displacement of the soft palate. The palate of 8 horses was injected with sodium tetradecyl sulfate under videoendoscopic guidance. Palatal sclerotherapy resulted in resolution of the respiratory noise in 7 horses, improvement of performance in 6 horses, and mild side effects in only 3 horses. This preliminary study suggests that palatal sclerotherapy is a safe, repeatable, inexpensive, and promising technique that should be considered as an alternative to existing treatments of intermittent dorsal displacement of the soft palate.

Treatment of habitual snoring with botulinum toxin: a pilot study.

The objective of this study was to investigate whether injections of botulinum toxin into the soft palate reduce snoring in a subgroup of patients that present an active process causing habitual snoring. The study was conducted in eight patients with habitual snoring but without evidence of obstructive sleep apnea. Polysomnography was performed for diagnostic purposes and to monitor sleep quality before and after treatment. The patients and their partners completed a questionnaire before and after treatment. Recordings of snoring noise before and after treatment were evaluated on a visual analog scale by a blinded assessor. Doses of 20 U of botulinum toxin type A (Dysport) were injected unilaterally into the muscles of the soft palate. Snoring was reduced in eight cases. The patients reported no major adverse effects. These results justify further studies of botulinum toxin therapy in patients with habitual snoring. The scheme presented for injections of botulinum toxin into the levator veli palatini muscle provides a rational basis for the design of such studies. Therapy with botulinum toxin for habitual snoring is safe, non-invasive, easy to perform, fully reversible, and thus warrants investigation under placebo-controlled, double-blind conditions. This treatment is appropriate for a disorder that is of paramount social importance but does not pose a medical threat to the individuals affected.

Clinical experience with angiotensin-converting enzyme inhibitor-induced angioedema.

OBJECTIVES: To understand the presentation and clinical course of angiotensin-converting enzyme (ACE) inhibitor-induced angioedema and to determine management factors associated with progression to airway compromise. STUDY DESIGN AND SETTING: Retrospective chart review of patients taking ACE inhibitors who presented to the emergency department with angioedema between December 1999 and July 2004 (n = 228). Clinical presentation, treatment, and clinical course were analyzed. RESULTS: The oral cavity was the most common location of upper-airway angioedema. Twenty-two (10%) patients required intubation, and all were intubated within 12 hours of presentation. Of the patients who required intubation, those who were started on an H(1)-blocker were extubated earlier than those not on an H(1)-blocker (P = 0.05). CONCLUSION: The locations of swelling and drooling on admission are predictive of the need for intubation. Other aspects of presentation, treatment, and disposition can help in management decisions for this potentially fatal condition. SIGNIFICANCE: This is the largest series to date of ACE inhibitor-related angioedema that challenges theories on the etiology and treatment of this condition.

Successful treatment of autophonia with botulinum toxin: case report.

OBJECTIVES: We sought to treat autophonia due to a patulous eustachian tube using botulinum toxin. METHODS: Because we assumed that the patulous eustachian tube was caused by abnormal activity of paratubal muscles (tensor and levator veli palatini muscles and salpingopharyngeus muscle), paralysis was performed via injection of botulinum toxin type A in a 45-year-old female professional musician who had had chronic unilateral autophonia for 20 years. In addition to a patient interview, an endoscopic examination of the nasopharynx (posterior rhinoscopy), ear microscopy, and impedance audiometry were performed to verify the diagnosis and the outcome after treatment. RESULTS: The autophonia disappeared 1 week after treatment. Normalized tympanic ventilation was verified by impedance audiometry after 8 weeks. The period of symptom relief was 9 months. CONCLUSIONS: The administration of botulinum toxin type A provides a new option in the treatment of patulous eustachian tube. The reliability of this method and the effect of repeated injections remains to be proved in future studies.