[Show abstract][Hide abstract] ABSTRACT: Treatment for esophageal dysmotility is currently limited to primarily pharmacologic intervention, which has questionable utility and frequently associated negative side effects. A potential behavioral intervention for esophageal dysmotility is the effortful oropharyngeal swallow. A previous pilot study using water perfusion manometry found an increase in distal esophageal amplitudes during effortful vs non-effortful swallowing. The current study sought to duplicate the previous study with improvements in methodology.
The effects of swallow condition (effortful vs non-effortful), sensor site, and gender on esophageal amplitude, duration, velocity, and bolus clearance were examined for 18 adults (nine males and nine females, mean age = 29.9 years) via combined solid-state manometry and intraluminal impedance.
The effortful swallow condition yielded significantly higher esophageal amplitudes across all sensor locations (P < 0.05). Further, the effortful swallowing decreased the risk of incomplete bolus clearance when compared with non-effortful swallowing (OR: 0.51; 95% CI: 0.30-0.86).
With improved manometric instrumentation, larger participant numbers, and methodology that controlled for potential confounding factors, this study confirms and advances the results of the previous pilot study: Volitional manipulation of the oropharyngeal phase of swallowing using the effortful swallow indeed affects esophageal physiology. Thus, the effortful swallow offers a behavioral manipulation of the esophageal phase of swallowing, and future studies will determine its clinical potential for treating esophageal dysmotility in patient populations.
Neurogastroenterology and Motility 03/2012; 24(3):252-6, e107-8. · 2.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We recently established that the SOD1-G93A transgenic mouse is a suitable model for oral-stage dysphagia in amyotrophic lateral
sclerosis (ALS). The purpose of the present study was to determine whether it could serve as a model for pharyngeal-stage
dysphagia as well. Electrophysiological and histological experiments were conducted on end-stage SOD1-G93A transgenic mice
(n=9) and age-matched wild-type (WT) littermates (n=12). Transgenic mice required a twofold higher stimulus frequency (40Hz) applied to the superior laryngeal nerve (SLN)
to evoke swallowing compared with WT controls (20Hz); transgenic females required a significantly higher (P<0.05) stimulus frequency applied to the SLN to evoke swallowing compared with transgenic males. Thus, both sexes demonstrated
electrophysiological evidence of pharyngeal dysphagia but symptoms were more severe for females. Histological evidence of
neurodegeneration (vacuoles) was identified throughout representative motor (nucleus ambiguus) and sensory (nucleus tractus
solitarius) components of the pharyngeal stage of swallowing, suggesting that pharyngeal dysphagia in ALS may be attributed
to both motor and sensory pathologies. Moreover, the results of this investigation suggest that sensory stimulation approaches
may facilitate swallowing function in ALS.
KeywordsAmyotrophic lateral sclerosis-ALS-Dysphagia-Superoxide dismutase-SOD1-G93A-Mouse Superior laryngeal nerve-Electrical stimulation-Deglutition-Deglutition disorders
[Show abstract][Hide abstract] ABSTRACT: There is an increasing interest in using mouse models for electrodiagnostic research. Studying transgenic mice with various pathologies adds to our knowledge of the natural history of a disease. It is imperative, however, to compare disease models with the appropriate control.
For these animals to be used in electrodiagnostic research, reference values must be set. If reference values are not available, the validity of data are highly questionable. We propose a method of obtaining mixed nerve action potentials and collect reference values from the sural nerve of mice.
The results were a mean peak latency of 1.74 msecs on the right and 1.89 msecs on the left. The mean amplitude was 17.0 microV on the left and 21.6 microV on the right.
In future studies, these reference values can be useful tools in analysis of murine subjects.
American journal of physical medicine & rehabilitation / Association of Academic Physiatrists 04/2009; 88(7):542-6. · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Relatively little is known about the underlying neuropathology of dysphagia in amyotrophic lateral sclerosis (ALS); thus, effective treatments remain elusive. Tremendous progress toward understanding and treating dysphagia in ALS may be possible through the use of an animal model of dysphagia in ALS research; however, no such animal model currently exists. The most logical candidate to consider is the SOD1-G93A transgenic mouse, the most widely investigated animal model of ALS. To investigate whether this animal model develops dysphagia, oral behaviors (lick and mastication rates) of SOD1-G93A transgenic mice (n = 30) were evaluated at three time points based on hind limb motor function: asymptomatic (60 days), disease onset (approximately 110 days), and disease end-stage (approximately 140 days). Age-matched nontransgenic littermates (n = 30) served as controls. At each time point, lick and mastication rates were significantly lower (p < 0.05) for transgenic mice compared with controls. Histologic analysis of the brainstem showed marked neurodegeneration (vacuolation) of the trigeminal and hypoglossal nuclei, two key motor components involved in mastication and licking behaviors. These results demonstrate a clinicopathologic correlation of oral dysfunction in SOD1-G93A transgenic mice, thereby establishing the SOD1-G93A transgenic mouse as a bona fide animal model of oral dysphagia in ALS.
[Show abstract][Hide abstract] ABSTRACT: The effect of an effortful swallow on the healthy adult esophagus was investigated using concurrent oral and esophageal manometry (water perfusion system) on ten normal adults (5 males and 5 females, 20-35 years old) while swallowing 5-ml boluses of water. The effects of gender, swallow condition (effortful versus noneffortful swallows), and sensor site within the oral cavity, esophageal body, and lower esophageal sphincter (LES) were examined relative to amplitude, duration, and velocity of esophageal body contractions, LES residual pressure, and LES relaxation duration. The results of this study provide novel evidence that an effortful oropharyngeal swallow has an effect on the esophageal phase of swallowing. Specifically, effortful swallowing resulted in significantly increased peristaltic amplitudes within the distal smooth muscle region of the esophagus, without affecting the more proximal regions containing striated muscle fibers. The findings pertaining to the LES are inconclusive and require further exploration using methods that permit more reliable measurements of LES function. The results of this study hold tremendous clinical potential for esophageal disorders that result in abnormally low peristaltic pressures in the distal esophageal body, such as achalasia, scleroderma, and ineffective esophageal motility. However, additional studies are necessary to both replicate and extend the present findings, preferably using a solid-state manometric system in conjunction with bolus flow testing on both normal and disordered populations, to fully characterize the effects of an effortful swallow on the esophagus.
[Show abstract][Hide abstract] ABSTRACT: Recent observations demonstrated that translation of mRNAs may occur in axonal processes at sites that are long distances away from the neuronal perikaria. While axonal protein synthesis has been documented in several studies, the mechanism of its regulation remains unclear. The aim of this study was to investigate whether RNA interference (RNAi) may be one of the pathways that control local protein synthesis in axons. Here we show that sciatic nerve contains Argonaute2 nuclease, fragile X mental retardation protein, p100 nuclease, and Gemin3 helicase-components of the RNA-induced silencing complex (RISC). Application of short-interfering RNAs against neuronal beta-tubulin to the sciatic nerve initiated RISC formation, causing a decrease in levels of neuronal beta-tubulin III mRNA and corresponding protein, as well as a significant reduction in retrograde labeling of lumbar motor neurons. Our observations indicate that RNAi is functional in peripheral mammalian axons and is independent from the neuronal cell body or Schwann cells. We introduce a concept of local regulation of axonal translation via RNAi.
The FASEB Journal 04/2007; 21(3):656-70. · 5.48 Impact Factor