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Biomedical subjects

R J Leonard

Publications and source records attributed to R J Leonard.

At least 19 recordsLinked to original sources

Hyoid movement during swallowing in older patients with dysphagia.

OBJECTIVES: To describe the timing, coordination, and extent of hyoid movement in a population of older adults with dysphagia and to evaluate the effect of hyoid movement on upper esophageal sphincter opening. DESIGN: A retrospective review of dynamic swallow studies performed between January 1996 and December 1999 was done. SUBJECTS: Patients included in the study were 65 years or older, without an obvious medical or surgical cause for their dysphagia. Timing and distance measures of hyoid movement from the patient population were compared with those from 60 younger (range, 18-62 years) and 23 older (range 67-83 years) control subjects without dysphagia using 1-way analysis of variance. Analysis of the effect of hyoid movement on upper esophageal sphincter opening was performed using contingency tables. RESULTS: In an older population with dysphagia, the coordination of swallowing gestures and bolus timing was intact, hyoid elevation was slow, and the duration of maximal hyoid elevation was reduced, but appropriate for the age of the patients. The hyoid bone elevated farther than normal for small bolus sizes, but the patients were unable to maintain this strategy in larger bolus swallows. CONCLUSION: An increased extent of hyoid displacement in older patients with dysphagia may represent a necessary compensation designed to minimize the effect of the short duration of hyoid elevation on the upper esophageal sphincter opening.

Adolescent↗

Pharyngeal constriction in elderly dysphagic patients compared with young and elderly nondysphagic controls.

This article reports the results of our study to determine the incidence of abnormalities in timing and extent of pharyngeal constriction in an elderly population with complaints of dysphagia. We performed a retrospective analysis of videofluoroscopic studies, i.e.. dynamic swallow studies, that were performed between 1996 and 1999. Included in the study were patients over 65 years old without an obvious medical or surgical cause for their dysphagia complaints. The timing of maximum pharyngeal constriction was measured relative to the onset of bolus pharyngeal transit, relative to the arrival of the bolus at the upper esophageal sphincter, and relative to the exit of the tail of the bolus from the upper esophageal sphincter. The extent of maximum pharyngeal constriction was measured from a lateral view. Patient data were compared with data gathered from young (18-62 years old) nondysphagic controls and with data gathered from elderly (67-83 years old) nondysphagic controls. We found that 73% of the patient population demonstrated incomplete pharyngeal constriction relative to controls, although the timing of pharyngeal constriction remained coordinated relative to the position of the bolus in the pharynx. Poor pharyngeal constriction, suggestive of pharyngeal weakness, contributed to 75% of the cases of aspiration.

Adult↗

Swallowing in myotonic muscular dystrophy: a videofluoroscopic study.

OBJECTIVES: (1) To determine how swallow function in patients with myotonic muscular dystrophy (MD) differs from that of healthy controls, (2) to identify the contributors to and predictors of improvement, and (3) to evaluate strategies that facilitate swallowing. DESIGN: Observational. SETTING: University medical center. PARTICIPANTS: Eighteen adults with myotonic MD (age range, 24-58 yr) and 60 healthy adult control subjects (age range, 18-73 yr). INTERVENTIONS: Swallow facilitation strategies. MAIN OUTCOME MEASURES: Between-group comparisons of mean bolus transit times, onsets of swallow gestures, and displacement measures obtained by dynamic lateral view videofluoroscopy. RESULTS: The MD patients' bolus transit times were significantly longer, and onsets of some swallow gestures were significantly delayed. Upper esophageal sphincter opening was prolonged (myotonic MD,.61 +/-.13s; control,.5 +/-.11s). Hyoid displacement was significantly less in men with myotonic MD (1.9 +/-.05 cm) than in male controls (2.4 +/-.68 cm); this difference was not observed between control and myotonic women. Of particular importance was the markedly reduced pharyngeal constriction found in the MD group. CONCLUSIONS: Weakness associated with the disease, as opposed to myotonia, was the most significant contributor to impairment. Persons at risk for aspiration may be identified by a measure of pharyngeal area. Selected strategies to facilitate pharyngeal clearing are worthwhile.

Adult↗

Bolus transit and airway protection coordination in older dysphagic patients.

OBJECTIVES/HYPOTHESIS: The intent of this study was to identify and characterize abnormalities of bolus pharyngeal transit and airway protection in a group of elderly patients with dysphagia. STUDY DESIGN: A retrospective analysis of dynamic videofluoroscopic swallowing studies performed in patients over the age of 65 was carried out. The study was limited to individuals with no obvious medical or surgical cause of dysphagia. METHODS: Pharyngeal bolus transit times were determined and compared with those from 60 young normal control subjects and 23 elderly control subjects. The timing of airway closure was analyzed in terms of bolus position in the pharynx. RESULTS: Prolonged bolus transit times were identified in 61% of patients investigated and 65% of elderly control subjects. Overall, the onset of airway closure was appropriate for the position of the bolus in the pharynx but was slow to achieve completion. Elderly control subjects were found to elevate the larynx early in the swallow. Delayed airway closure was identified as a contributor to aspiration in some dysphagic subjects. CONCLUSIONS: Pharyngeal transit of the bolus may be prolonged in elderly individuals. Swallowing coordination mechanisms appear to be intact in the majority of elderly patients with dysphagia, but gestures may be weak and ineffective. Early laryngeal elevation may be an effective strategy to avoid aspiration.

Aged↗

Accommodation to changes in bolus viscosity in normal deglutition: a videofluoroscopic study.

Videofluoroscopic swallow studies were performed on 60 normal adult volunteers. Swallowing variables were measured during swallows of a 3-cm3 paste bolus and a 3-mL liquid bolus and were compared to identify changes in swallow gesture displacement and timing, as well as changes in bolus movement timing. The study revealed that some differences measured by videofluoroscopy appear to be the result of the inherent bolus characteristics, while others likely represent changes in swallow gestures needed to accommodate variations in bolus viscosity. The overall timing of pharyngeal transit did not vary between bolus types. Oropharyngeal transit trended toward being faster for a liquid bolus with a concurrent early elevation of the aryepiglottic folds. The hyoid bone elevated at the same time, at the same rate, and to the same extent irrespective of bolus viscosity. During a liquid bolus swallow, the hyoid bone trended toward a more prolonged elevation, corresponding to prolonged pharyngoesophageal sphincter opening. The pharyngoesophageal sphincter, however, opened to a greater extent with a paste bolus.

Adolescent↗

Adenosine: A partial agonist of the growth hormone secretagogue receptor.

The growth hormone secretagogue receptor (GHS-R) is involved in the regulation of pulsatile GH release. However, until recently, natural endogenous ligands for the receptor were unknown. We fractionated porcine hypothalamic extracts and assayed fractions for activity on HEK293 cells expressing GHS-R and aequorin. A partial agonist was isolated and identified using microspray tandem mass spectrometry as adenosine. GHS-R activation by adenosine and synthetic adenosine agonists is inhibited by the GHS-R selective antagonists L-765,867, D-Lys(3)-GHRP-6, and by theophylline and XAC. Cross desensitization of the GHS-R occurs with both MK-0677 and adenosine. Ligand binding and site directed mutagenesis studies show that adenosine binds to a binding site that is distinct from the previously characterized MK-0677 and GHRP-6 binding pocket. We propose, that adenosine is a physiologically important endogenous GHS-R ligand and speculate that GHS-R ligands modulate dopamine release from hypothalamic neurons.

Adenosine↗

Timing of events in normal swallowing: a videofluoroscopic study.

Dynamic videofluoroscopic swallow studies were performed on 60 normal adult volunteers to establish normative data for clinically useful timing measures. The relation of swallowing gesture timing to the timing of actual bolus transit was of particular interest because it provides insight into the physiology of larger bolus volume accommodation. Parameters evaluated include the timing of bolus pharyngeal transit, soft palate elevation, aryepiglottic fold elevation and supraglottic closure, arrival of the bolus in the vallecula, hyoid bone displacement onset and duration, arrival of the bolus at the pharyngoesophageal sphincter, maximum pharyngeal constriction, and pharyngoesophageal sphincter opening. These parameters represent events required for normal deglutition, can be used to identify abnormalities in dysphagic patients, and provide a basis for comparison of swallowing performance both within and between patients. In addition, our experience has shown them to be reliably obtained. Other investigators have reported some of the measurements. However, to our knowledge, normative data for timing of aryepiglottic fold elevation, soft palate elevation and closure, and maximum pharyngeal constriction have not been described. Other measures included in the present study may provide alternatives when conventional measures cannot be obtained in selected patients. The relevance and clinical utility of new and alternative measures, in particular, are discussed.

Adolescent↗

Structural displacements in normal swallowing: a videofluoroscopic study.

Dynamic videofluoroscopic swallow studies were performed on 60 normal adult volunteers to establish normative data for displacement of upper aerodigestive tract structures during deglutition. Variables evaluated included hyoid bone displacement, larynx-to-hyoid bone approximation, pharyngeal constriction, and the extent of pharyngoesophageal sphincter (PES) opening during liquid swallows of 1, 3, and 20 cc. Results showed direct relationships between bolus size and hyoid displacement, between bolus size and PES opening, and between bolus size and pharyngeal constriction. Only hyoid-to-larynx approximation remained unchanged across bolus sizes. Sex differences were noted for all variables except PES opening. Reliability for most measurement variables was excellent. To our knowledge, normative data for pharyngeal constriction and larynx-to-hyoid approximation have not previously been described.

Adolescent↗

Timing of swallowing events after single-modality treatment of head and neck carcinomas with radiotherapy.

This paper reports the results of a preliminary study designed to evaluate swallowing function in 20 patients 1 year after successful treatment of head and neck carcinomas with radiotherapy. The timing of swallowing events was evaluated by videofluoroscopy. The mean values for each measure were compared to the normative data from 60 control subjects. The radiotherapy patients demonstrated prolonged pharyngeal bolus transit and a delay of laryngeal closure. Hyoid bone elevation began late relative to the onset of bolus movement. A strong trend toward a delay in hyoid elevation relative to bolus movement was demonstrated. The time required for the hyoid bone to reach maximal elevation did not differ from that in normals, but the hyoid was held in an elevated position for a longer period of time. As a result of changes in hyoid movement, the upper esophageal sphincter tended to open early relative to the arrival of the bolus. In conclusion, changes in deglutition occur after radiotherapy, presumably as an adaptation to changes in tissue compliance.

Carcinoma↗

Structural mobility in deglutition after single modality treatment of head and neck carcinomas with radiotherapy.

BACKGROUND: The results of a preliminary study designed to evaluate swallowing function in patients 1 year after successful treatment of head and neck carcinomas with radiotherapy are reported. METHODS: Movement of the velum, hyoid, larynx, tongue base, and posterior pharyngeal wall were objectively assessed by dynamic videofluoroscopy. Mean values of each swallowing parameter measured from the study group were compared with normative data from a group of 60 normal control subjects. The radiotherapy patient group was divided based on the location of the primary tumor in an attempt to correlate the effect of tumor location on swallowing. RESULTS: Hyoid displacement was decreased in radiotherapy patients and the hyoid elevated maximally independent of bolus size, unlike control subjects, in whom hyoid displacement increased with increases in bolus size. Patients with tongue base tumors demonstrated decreased pharyngeal constriction compared with patients with larynx and pharynx/nasopharynx tumors. CONCLUSIONS: A generalized decrease in the mobility of pharyngeal structures is demonstrated after radiotherapy.

Deglutition↗

Margatoxin binds to a homomultimer of K(V)1.3 channels in Jurkat cells. Comparison with K(V)1.3 expressed in CHO cells.

Voltage-gated potassium (K(V)) channels play key roles in setting the resting potential and in the activation cascade of human peripheral T lymphocytes. Margatoxin (MgTX), a 39-amino acid peptide from Centruroides margaritatus, is a potent inhibitor of lymphocyte K(V) channels. The binding of monoiodotyrosinyl margatoxin ([125I]MgTX) to plasma membranes prepared from either Jurkat cells, a human leukemic T cell line, or CHO cells stably transfected with the Shaker-type voltage-gated K+ channel, K(V)1.3, has been used to investigate the properties of lymphocyte K(V) channels. These data were compared with [125I]MgTX binding to heterotetrameric K(V) channels in rat brain synaptic plasma membranes [Knaus, H. G., et al. (1995) Biochemistry 34, 13627-13634]. The affinity for [125I]MgTX is 100-200 fM in either Jurkat or CHO/K(V)1.3 membranes, and the receptor density is 20-120 fmol/mg in Jurkat membranes or 1000 fmol/mg in CHO/K(V)1.3 membranes. In contrast to rat brain, [125I]MgTX binding to Jurkat and CHO/K(V)1.3 membranes exhibits an absolute requirement for K+, with no potentiation of binding by Na+. K(V)1.3 was the only K(V)1 series channel present in either CHO/K(V)1.3 or Jurkat plasma membranes as determined by immunoprecipitation of [125I]MgTX binding or by Western blot analyses using sequence-specific antibodies prepared against members of the K(V)1 family. The relative potencies of a series of peptidyl K(V) channel inhibitors was essentially the same for inhibition of [125I]MgTX binding to Jurkat, CHO, or rat brain membranes and for blocking 86Rb+ efflux from the CHO/K(V)1.3 cells, except that alpha-dendrotoxin was more potent at blocking binding to rat brain membranes than in the other assays. The characteristics of [125I]MgTX binding, the antibody profiles, and the effects of the peptidyl K(V) inhibitors all indicate that the [125I]MgTX receptor in Jurkat lymphocytes is comprised of a homomultimer of K(V)1.3, unlike the heteromultimeric arrangement of the receptor in rat brain.

Animals↗