Association of Miglustat With Swallowing Outcomes in Niemann-Pick Disease, Type C1.

Importance: Niemann-Pick disease, type C1 (NPC1) is a progressive neurovisceral disease with no US Food and Drug Administration-approved therapy. Miglustat, a drug used off-label in the United States for the treatment of NPC1, appears to stabilize neurologic disease progression. Several prospective trials suggest that miglustat stabilizes oropharyngeal swallowing function; however, its effect on dysphagia and aspiration risk has not been demonstrated instrumentally. Objective: To determine if miglustat therapy is associated with stabilized swallowing dysfunction in individuals with NPC1. Design, Setting, and Participants: Patients with confirmed NPC1 diagnoses were evaluated in a single-center cohort study of NPC1 from April 1997 to November 2019. Longitudinal data from individuals with neurologic disease onset prior to age 15 years were analyzed. The study population was divided into those with neurologic disease onset in early childhood (age <6 years) and late childhood (age ≥6 years and <15 years). Analysis began September 2019. Exposures: Oral miglustat at baseline and at follow-up. Main Outcomes and Measures: Oropharyngeal swallowing function was assessed with videofluoroscopic swallowing studies. Overall swallowing ability and aspiration risk were evaluated using the American Speech-Language-Hearing Association National Outcome Measurement System swallowing domain and an adapted Rosenbek aspiration-penetration scale, respectively. Results: Overall, 50 participants were evaluated at baseline (median [interquartile range] age, 9.4 [3.4-16.4] years; 26 [52%] female). The median (interquartile range) duration of follow-up was 3.0 (1.1-4.4) years. Miglustat use was associated with decreased odds of worse American Speech-Language-Hearing Association National Outcome Measurement System swallowing domain outcomes in all 3 subsets (overall: odds ratio [OR], 0.09 [95% CI, 0.02-0.36); P < .001; early childhood: OR, 0.17 [95% CI, 0.04-0.67]; P = .01; late childhood: OR, 0.05 [95% CI, 0.01-0.29]; P = .001). Miglustat use was associated with decreased odds of worse Rosenbek aspiration-penetration scale outcomes in the overall cohort (OR, 0.28 [95% CI, 0.08-0.95]; P = .04) but not in each subgroup (early childhood: OR, 0.27 [95% CI, 0.06-1.22]; P = .09; late childhood: OR, 0.38 [95% CI, 0.06-2.33]; P = .29). Conclusions and Relevance: These data suggest that miglustat use is associated with stabilized swallowing function and reduced aspiration risk in NPC1, thus supporting its use in this population. In addition, these data demonstrate that a quantification of swallowing dysfunction can be used as a clinically relevant, functional outcome measure in future therapeutic trials in NPC1.

A Double-Blind Randomized Controlled Trial to Determine the Preventive Effect of Hangekobokuto on Aspiration Pneumonia in Patients Undergoing Cardiovascular Surgery.

PURPOSE: This study aimed to assess whether hangekobokuto (HKT) can prevent aspiration pneumonia in patients undergoing cardiovascular surgery. METHODS: We performed a single-center, double-blinded, randomized, placebo-controlled study of HKT in patients undergoing cardiovascular surgery. JPS HKT extract granule (JPS-16) was used as HKT. The primary endpoint was defined as the prevention of postoperative aspiration pneumonia. The secondary endpoints included complete recovery from swallowing and coughing disorders. RESULTS: Between August 2014 and August 2015, a total of 34 patients were registered in this study. The rate of subjects with postoperative aspiration pneumonia was significantly lower in the HKT group than in the placebo group (p = 0.017). In high-risk patients for aspiration pneumonia, the rate was significantly lower in the HKT group than in the placebo group (p = 0.015). The rate of subjects with swallowing disorders tended to be lower in the HKT group than in the placebo group (p = 0.091), and in high-risk patients, the rate was significantly lower in the HKT group than in the placebo group (p = 0.038). CONCLUSIONS: HKT can prevent aspiration pneumonia in patients undergoing cardiovascular surgery. In high-risk patients for aspiration pneumonia, HKT can prevent aspiration pneumonia and improve swallowing disorders.

Effects of capsaicin on swallowing function in stroke patients with dysphagia: A randomized controlled trial.

BACKGROUND/AIMS: Dysphagia is a common complication after acute stroke. While there are several innovative treatments being tested to improve the swallowing function of stroke patients with dysphagia, our aim is to explore the use of readily available natural capsaicin in stroke patients with dysphagia. STUDY DESIGN: A randomized, double-blind study. METHODS: Sixty-nine hospitalized stroke patients were enrolled in this study. The capsaicin intervention group received thermal tactile stimulation with supplementation of natural capsaicin and additional nectar viscosity boluses. The control group received stimulation and boluses with placebo. Swallowing function was evaluated before and after the 3-week treatment, using Volume-Viscosity Swallow Test, Eating Assessment Tool, Standardized Swallowing Assessment, and Water Swallow Test. RESULTS: The score decreases in the Eating Assessment Tool and Standardized Swallowing Assessment of the capsaicin intervention group were significantly greater than that of the placebo control group (P < .01). Among the 60 patients, the capsaicin intervention group exhibited effectiveness in a higher number of patients (n = 27, 90%) than the placebo group (n = 9, 30%, P < .001). CONCLUSIONS: Regular use of natural capsaicin could promote the recovery of swallow function in stroke patients with dysphagia. The ample availability of natural capsaicin could provide a low cost, easily accessible, and safe alternative method to address dysphagia in stoke patients.

Study on the salivation effect of encapsulated food products containing Sichuan pepper oil.

Sichuan pepper is a plant belonging to the genus Zanthoxylum and family rue. To evaluate whether Sichuan pepper oil boosts saliva secretion using an encapsulated food product containing the oil in subjects presenting with mouth dryness. We evaluated subjective symptoms that changed with a decrease in salivary secretion in the subjects by evaluating the number of Candida colonies and by conducting interviews. The study results demonstrated that salivary secretion increased by 39.4% ± 37.6% after single ingestion of the product, and an additional 8.7% ± 13.2% and 6.3% ± 31.2% following continuous ingestion over 2 and 4 weeks, respectively. These findings suggested that the product rapidly promotes and maintains salivation. Regarding the proliferation of Candida colonies in subjects with mouth dryness, a negative correlation was observed between Candida colony number and salivary secretion quantity. Additionally, interviews revealed that subjective symptoms, such as mouth dryness, discomfort and pain in the mouth, difficulty swallowing the saliva, and feeling of stickiness in the mouth, improved shortly after single ingestion of the product, and mouth dryness was reduced by continuous consumption of the product. These findings indicated that the product studied promotes rapid salivary secretion, is effective in reducing the number of oral Candida colonies, and improves subjective symptoms such as mouth dryness.

Impact of Peppermint Therapy on Dysphagia and Non-cardiac Chest Pain: A Pilot Study.

BACKGROUND: Due to its smooth muscle relaxing properties, peppermint oil (PO) may relieve dysphagia and chest pain due to esophageal motility disorders. AIM: To explore the impact of PO on dysphagia and/or chest pain in patients referred for motility testing. METHODS: Patients initiated on PO for dysphagia and/or chest pain from 2013 to 2016 were identified. We excluded patients with obstructing esophageal lesions, patients lost to follow-up, and those with preexisting cardiac conditions. Concentrated PO was given as commercially available dissolvable peppermint tablets; two tablets before meals were prescribed to patients with dysphagia and on an as-needed basis for patients with chest pain. Patient-reported symptom response was assessed using a modified five-point Likert scale. RESULTS: Thirty-eight patients were included. Twenty-four patients (63%) reported improvement; 12 were much better and 12 were slightly better. Fourteen experienced no change and none reported feeling worse. Based on pre-treatment HRM, patients with distal esophageal spasm (DES) (n = 10) and esophagogastric junction outflow obstruction (EGJOO) (n = 8) appeared to demonstrate the best subjective improvement (83% and 100%, respectively) (P < 0.05). CONCLUSION: PO appears to provide symptomatic relief in some patients with dysphagia and CP. Presence of a well-defined manometric disorder, particularly DES or EGJOO, appeared to predict response.

Effect of electro-acupuncture on regulating the swallowing by activating the interneuron in ventrolateral medulla (VLM).

Ventrolateral medulla(VLM) was one of the essential part of central pattern generator(CPG) in swallowing and electro-acupuncture(EA) was an important intervention in swallowing disorder. But the effect and mechanism of EA at acupoints on swallowing were unknown. The present aim to detect the effect of EA at Lianquan (CV23) on swallowing and swallowing-related(SR) interneuron in VLM. Thirty-six Sprague-Dawley rats were operated and the swallowing reflex was induced through Double distilled water (DDW) infusion. Simultaneously, the numbers of swallowing were recorded. Then EA was given at Lianquan and Neiguan (PC6) and the neuron discharges in VLM were detected. A total of 72 neurons were recorded, 60 of which were correctly recorded after histology identification. Two types of SR neurons were found and the numbers of swallowing increased after EA at CV23 and PC6 compared with no EA group. The neuron response rates were 78.3% and 50% for EA at CV23 and PC6 respectively with significant difference (P < 0.05). Meanwhile, the neuron spike patterns were changed after EA at CV23 and PC6. In addition, twenty-four rats were used for immunofluorescence after EA at CV23 and PC6. The results showed that c-fos positive cells in CV23 group were 20.63±2.35, while PC6 group was 14.13±1.78 and 6.88±1.42 in control group. There were significant difference between them (P < 0.05). These results indicated that EA could regulate the swallowing function via activating the SR interneurons in VLM under the physiological condition.

Aural stimulation with capsaicin ointment improved swallowing function in elderly patients with dysphagia: a randomized, placebo-controlled, double-blind, comparative study.

OBJECTIVE: The aim of this study was to assess whether aural stimulation with ointment containing capsaicin improves swallowing function in elderly patients with dysphagia. STUDY DESIGN: A randomized, placebo-controlled, double-blind, comparative study. SETTINGS: Secondary hospital. PATIENTS AND METHODS: Twenty elderly dysphagic patients with a history of cerebrovascular disorder or Parkinson's disease were randomly divided into two groups: 10 receiving aural stimulation with 0.025% capsaicin ointment and 10 stimulated with placebo. The ointments were applied to the external auditory canal with a cotton swab. Then, swallowing of a bolus of blue-dyed water was recorded using transnasal videoendoscopy, and the swallowing function was evaluated according to both endoscopic swallowing scoring and Sensory-Motor-Reflex-Clearance (SMRC) scale. RESULTS: The sum of endoscopic swallowing scores was significantly decreased 30 and 60 min after a single administration in patients treated with capsaicin, but not with placebo. Reflex score, but not Sensory, Motion and Clearance scores, of the SMRC scale was significantly increased 5, 30 and 60 min after single administration in patients treated with capsaicin, but not with placebo. No patient showed signs of adverse effects. CONCLUSION: As capsaicin is an agonist of the transient receptor potential vanilloid 1 (TRPV1), these findings suggest that improvement of the swallowing function, especially glottal closure and cough reflexes, in elderly dysphagic patients was due to TRPV1-mediated aural stimulation of vagal Arnold's nerve with capsaicin, but not with a nonspecific mechanical stimulation with a cotton swab.

Effects of Capsaicin on Older Patients with Oropharyngeal Dysphagia: A Double-Blind, Placebo-Controlled, Crossover Study.

BACKGROUND/AIMS: The standard of care for older patients with oropharyngeal dysphagia (OD) is poor. Stimulation of transient receptor potential vanilloid 1 might become a pharmacological strategy for these patients. This study aimed to compare the therapeutic effect of film food containing 0.75 µg of capsaicin in these patients. METHODS: In a crossover, randomized trial, 49 patients with OD were provided capsaicin or identical placebo at least 7 days apart. Patients' reported symptoms during repeated swallowing, the volume, pH and substance P (SP) concentrations in saliva, and cervical esophageal wall motion evaluated by ultrasonographic tissue Doppler imaging were obtained before and after capsaicin or placebo administration. RESULTS: Significantly more patients with OD who took capsaicin experienced improvement in symptoms than those who took placebo. Salivary SP levels were significantly increased after capsaicin administration compared with placebo in the effective group. The duration of cervical esophageal wall opening was significantly shorter in capsaicin administration in the effective group. Furthermore, a significant negative correlation was found between the duration of cervical esophageal wall opening and salivary SP levels. CONCLUSION: Elevated salivary SP concentrations stimulated by capsaicin greatly improve the safety and efficacy of swallowing, and shorten the swallow response in older patients with OD.

Ginger Orally Disintegrating Tablets to Improve Swallowing in Older People.

We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (p<0.05). Among 10 subjects, one scored 1-3 using the four evaluation criteria. Overall, no aspiration occurred and a significant improvement in the swallowing function score was observed (p<0.05) after taking the ginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function.

Botulinum toxin for upper oesophageal sphincter dysfunction in neurological swallowing disorders.

BACKGROUND: Adequate upper oesophageal sphincter (UOS) opening is critical to safe and efficient swallowing due to the close proximity of the UOS to the airway entrance. Many people with neurological conditions, progressive and non-progressive, present with UOS dysfunction. The consequences for the person include difficulty swallowing food with subsequent choking and aspiration (passage of material into the trachea beyond the level of the true vocal cords). Clinical complications include aspiration pneumonia, weight loss, dehydration and malnutrition. Tube feeding is often indicated but is associated with increased mortality. Quality of life is also frequently impacted. A range of interventions exist that aim to improve UOS function and swallowing. These include compensatory strategies, rehabilitation techniques, pharmacological interventions and surgery. Over the last two decades, botulinum toxin has been gaining popularity as an intervention for UOS dysfunction, with some evidence to suggest that it is successful in improving swallow function. Despite a number of studies investigating its efficacy, there is a lack of consensus regarding whether this intervention is effective in improving swallowing for individuals with UOS dysfunction associated with neurological disease. OBJECTIVES: To establish the efficacy and safety of botulinum toxin use aimed at improving UOS dysfunction in people with swallowing difficulties (dysphagia) associated with non-progressive and progressive neurological disease. SEARCH METHODS: We searched the following electronic databases for published trials: the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (1950 to 2013); EMBASE (1980 to 2013); AMED (Allied and Complementary Medicine) (1941 to 2013); CINAHL (Cumulative Index to Nursing and Allied Health Literature) (1937 to 2013). We also searched major clinical trials registers: CCT (http://www.controlled-trials.com); Clinical Trials (http://www.clinicaltrials.gov); Chinese Clinical Trial Register (www.chictr.org); ACTR (http://www.actr.org.au/. We examined the reference lists of all potentially relevant studies to identify further relevant trials. We handsearched published abstracts of conference proceedings from both the Dysphagia Research Society and the European Society of Swallowing Disorders. Digestive Disease Week (published in Gastroenterology) was also handsearched. Additionally, we searched ProQuest Dissertations & Theses for dissertation abstracts. SELECTION CRITERIA: Only randomised controlled trials were sought. DATA COLLECTION AND ANALYSIS: Independent searches were completed by JR, AM, MC and MW. Two review authors (JR and MW) independently inspected titles, abstracts and key words identified from the literature search. MAIN RESULTS: No randomised controlled studies were retrieved. Twenty-nine studies were excluded, mainly on the basis of trial design. AUTHORS' CONCLUSIONS: It was not possible to reach a conclusion on the efficacy and safety of botulinum toxin as an intervention for people with UOS dysfunction and neurological disease. There is insufficient evidence to inform clinical practice. Directions for future research are provided.

Effect of oral piperine on the swallow response of patients with oropharyngeal dysphagia.

BACKGROUND: Oropharyngeal dysphagia (OD) is a major gastrointestinal motility disorder that causes severe nutritional and respiratory complications in elderly and neurological patients. In an earlier study, we found that stimulation of pharyngeal sensory neurons by capsaicinoids acting on transient receptor potential vanilloid 1 (TRPV1) improved the swallow response of dysphagic patients. The aim of this study was to explore the effect of piperine, a dual TRPV1/TRPA1 agonist, on the swallow response of dysphagic patients. METHODS: A videofluoroscopic study was performed to assess the signs of impaired safety and efficacy of swallow and the swallow response of 40 dysphagic patients while swallowing one series of nectar control boluses and two series of nectar boluses supplemented with piperine. Patients were randomized into two groups: one group received 150 µM piperine and the other group received 1 mM. RESULTS: Piperine improved the safety of swallow by: (a) reducing the prevalence of unsafe swallows by -34.48% (P = 0.004) at 150 µM and -57.19% (P < 0.001) at 1 mM, and the severity score of the penetration-aspiration scale from 3.25 ± 0.51 to 1.85 ± 0.27 (P = 0.003, 1 mM); and (b) shortening the time to laryngeal vestibule closure from 0.366 ± 0.024 to 0.270 ± 0.022 s with 150 µM piperine (P < 0.001) and from 0.380 ± 0.032 to 0.306 ± 0.028 s with 1 mM piperine (P < 0.05). CONCLUSIONS: Supplementing the alimentary bolus with piperine speeds swallow response and strongly improves safety of swallow in patients with OD, with a maximal therapeutic effect at 1 mM. Our results suggest that activation of TRPV1/A1 in oropharyngeal sensory neurons is a very promising neurostimulation strategy for dysphagic patients.

Complementary and integrative treatments: swallowing disorders.

Swallowing disorders are associated with many disease processes and are associated with significant morbidity and mortality. This article provides information regarding the various causes of swallowing disorders as well as medical, surgical, and integrative approaches to their management.

Natural capsaicinoids improve swallow response in older patients with oropharyngeal dysphagia.

OBJECTIVE: There is no pharmacological treatment for oropharyngeal dysphagia (OD). The aim of this study was to compare the therapeutic effect of stimulation of oropharyngeal transient receptor potential vanilloid type 1 (TRPV1) with that of thickeners in older patients with OD. DESIGN: A clinical videofluoroscopic non-randomised study was performed to assess the signs of safety and efficacy of swallow and the swallow response in (1) 33 patients with OD (75.94 ± 1.88 years) while swallowing 5, 10 and 20 ml of liquid (20.4 mPa.s), nectar (274.4 mPa.s), and pudding (3930 mPa.s) boluses; (2) 33 patients with OD (73.94 ± 2.23 years) while swallowing 5, 10 and 20 ml nectar boluses, and two series of nectar boluses with 150 µM capsaicinoids and (3) 8 older controls (76.88 ± 1.51 years) while swallowing 5, 10 and 20 ml nectar boluses. RESULTS: Increasing bolus viscosity reduced the prevalence of laryngeal penetrations by 72.03% (p < 0.05), increased pharyngeal residue by 41.37% (p < 0.05), delayed the upper esophageal sphincter opening time and the larynx movement and did not affect the laryngeal vestibule closure time and maximal hyoid displacement. Treatment with capsaicinoids reduced both, penetrations by 50.% (p < 0.05) and pharyngeal residue by 50.% (p < 0.05), and shortened the time of laryngeal vestibule closure (p < 0.001), upper esophageal sphincter opening (p < 0.05) and maximal hyoid and laryngeal displacement. CONCLUSION: Stimulation of TRPV1 by capsaicinoids strongly improved safety and efficacy of swallow and shortened the swallow response in older patients with OD. Stimulation of TRPV1 might become a pharmacologic strategy to treat OD.

Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer.

PURPOSE: To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. PATIENTS AND METHODS: Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point. RESULTS: Five hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio [HR], 0.75; 95% CI, 0.59 to 0.95; P = .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P = .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemotherapy (HR, 1.25; 95% CI, 0.98 to 1.61; P = .08). Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT (HR, 0.58; 95% CI, 0.37 to 0.89; P = .0050) and over RT alone (P < .001), whereas induction PF followed by RT was not better than treatment with RT alone (HR, 1.26; 95% CI, 0.88 to 1.82; P = .35). No difference in late effects was detected, but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% v 20.8% with induction chemotherapy and 16.9% with RT alone). CONCLUSION: These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS. Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone. New strategies that improve organ preservation and function with less morbidity are needed.

Evaluation of the efficacy of two mouthrinses formulated for the relief of xerostomia of diverse origin in adult subjects.

OBJECTIVE: To evaluate the efficacy of two new mouthrinses in the reduction of xerostomía-associated symptomatology. BACKGROUND: Xerostomia is a common chronic health condition that affects a great number of adults and significantly deteriorates quality of life, such that treatment is necessary. MATERIALS AND METHODS: Sixty-seven adult subjects of both sexes presenting xerostomia of diverse origin were selected. Mouthrinses were tested using a double-blind, randomized, cross-over clinical trial with an intervining wash out period. RESULTS: The 100% of subjects presented sensation of dry mouth, and 86% stated sensation of thick saliva. Burning tongue sensation, need to drink liquids to swallow and the sensation of swallowing difficulty were recorded in more than 50% of the patients. The most frequent pathologies in the sample were depression, arthritis, and arterial hypertension. Results of the clinical tests showed that mouthrinse 1 relieves sensation of dry mouth, need to drink liquids, and swallowing difficulty. In contrast, mouthrinse 2 relieves only latter two symptoms. Both rinses were more effective in relieving xerostomía-associated symptomatology in patients taking 3 or more medicines simultaneously. CONCLUSION: Both mouthrinses were effective in relieving various xerostomia symptoms, could be distributed at a low cost, thereby improving the quality of life of population affected.

Sensory stimulation to improve swallowing reflex and prevent aspiration pneumonia in elderly dysphagic people.

Morbidity and mortality from aspiration pneumonia continues to be a major health problem in the elderly. A swallowing disorder, such as a delayed triggering of the swallowing reflex, exists in patients with aspiration pneumonia. We found that the swallowing reflex in elderly people was temperature-sensitive. The swallowing reflex was delayed when the temperature of the food was close to body temperature. The actual swallowing time shortened when the temperature difference increases. The improvement of swallowing reflex by temperature stimuli could be mediated by the temperature-sensitive transient receptor potential (TRP) channel. The administration of a pastille with capsaicin as an agonist stimulus of TRPV1, a warm-temperature receptor, decreased the delay in swallowing reflex. Food with menthol, an agonist of TRPM8, a cold-temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimulation such as black pepper was useful to improve the swallowing reflex for people with low activity of daily living (ADL) levels or with decreased consciousness. Oral care also shortened the latent time of swallowing reflex presumably due to stimulating the nociception of the oral cavity. A combination of these sensory stimuli may improve the swallowing disorders and prevent aspiration pneumonia.

Comparison of two different local anaesthetic infiltrations for postoperative pain relief in tonsillectomy: a prospective, randomised, double blind, clinical trial.

In previous studies, it was shown that the post-tonsillectomy wound infiltration of bupivacaine can reduce postoperative pain. The objective of this study is to determine whether the postoperative wound infiltration with a mixture of bupivacaine, mepivacaine and adrenaline is more effective than the sole application of bupivacaine. A prospective, double-blind, randomized, control study included 30 patients scheduled for "cold steel" tonsillectomy. All patients obtained post-tonsillectomy infiltration of 6.25 mg bupivacaine alone on one side and 3.75 mg bupivacaine, 25 mg mepivacaine and 0.0125 mg epinephrine on the other side (intra-individual study design). Intake of analgesics and postoperative pain was assessed 0-6 days after surgery by visual analogue scale in inactivity and during swallowing by the nurse staff. Bleeding, dysphagia, pain, aspiration or extraordinary pain sensation were registered by the patient. The pain scores did not differ between the groups. All patients received systemic painkillers; 6 (20%) patients needed intravenous analgesics. Postoperative haemorrhage occurred in two patients without correlation to a certain local anaesthetic. Two patients developed sinus tachycardia for 2.5 min after epinephrine infiltration. Because of cost-effectiveness and complication rates, we recommend only post-tonsillectomy wound infiltration of bupivacaine. The injection should be placed in superficial muscle and connective tissue. A stringent systemic analgesia regime is indispensable for pain relief after tonsillectomy.

Long-term miglustat therapy in children with Niemann-Pick disease type C.

Niemann-Pick disease type C is a rare, genetic disease associated with impaired intracellular lipid trafficking and progressive neurological symptoms. Miglustat slowed disease progression in a 12-month randomized trial in juveniles and adults with Niemann-Pick disease type C, and in a parallel, noncontrolled study in affected children. Here, the authors report the open-label extension to the pediatric study. Patients aged 4 to 12 years received open-label miglustat (dose adjusted for body surface area) for an initial 12 months, during a further 12-month extension, and a long-term, continued extension phase. Efficacy assessments included horizontal saccadic eye movement, swallowing, and ambulation. Ten children completed 24 months' treatment. Horizontal saccadic eye movement, ambulation, and swallowing were stabilized at 24 months. Analysis of key parameters of disease progression showed disease stability in 8 of 10 patients (80%). Miglustat stabilized neurological disease progression in pediatric patients with Niemann-Pick disease type C, with comparable safety and tolerability to that observed in adults and juveniles.

BDNF-TrkB signaling interacts with the GABAergic system to inhibit rhythmic swallowing in the rat.

Brain-derived neurotrophic factor (BDNF) acts as an anorexigenic factor in the dorsal vagal complex (DVC) of the adult rat brain stem. The DVC contains the premotoneurons controlling swallowing, a motor component of feeding behavior. Although rats with transected midbrain do not seek out food, they are able to swallow and to ingest food. Because BDNF and tropomyosin-related kinase B (TrkB) receptors are expressed in the DVC, this study hypothesized that BDNF could modify the activity of premotoneurons involved in swallowing. Repetitive electrical stimulation of the superior laryngeal nerve (SLN) induces rhythmic swallowing that can be recorded with electromyographic electrodes inserted in sublingual muscles. We show that a microinjection of BDNF in the swallowing network induced a rapid, transient, and dose-dependant inhibition of rhythmic swallowing. This BDNF effect appeared to be mediated via TrkB activation, since it no longer occurred when TrkB receptors were antagonized by K-252a. Interestingly, swallowing was inhibited when subthreshold doses of BDNF and GABA were coinjected, suggesting a synergistic interaction between these two signaling substances. Moreover, BDNF no longer had an inhibitory effect on swallowing when coinjected with bicuculline, a GABA(A) receptor antagonist. This blockade of BDNF inhibitory effect on swallowing was reversible, since it reappeared when BDNF was injected 15 min after bicuculline. Finally, we show that stimulation of SLN induced a decrease in BDNF protein within the DVC. Together, our results strongly suggest that BDNF inhibits swallowing via modulation of the GABAergic signaling within the central pattern generator of swallowing.