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Biomedical subjects

C N Ford

Publications and source records attributed to C N Ford.

At least 19 recordsLinked to original sources
PubMed2000

Resistance to botulinum toxin injections for spasmodic dysphonia.

A known complication of botulinum toxin injections in the treatment of dystonia has been the occasional development of resistance. This has been seen primarily with patients who receive injections for torticollis. We report on 2 patients who, after several years of receiving injections for spasmodic dysphonia, developed clinical resistance by failing to have expected voice improvement after receiving laryngeal reinjection. One of the 2 patients demonstrated antibodies to botulinum toxin by mouse neutralization bioassay. The second patient had negative bioassay results but had no clinical response to the test toxin injection of facial muscles. These cases demonstrate that, although uncommon, resistance to botulinum toxin injections can occur in the treatment of spasmodic dysphonia. We offer suggestions to limit this complication.

Animals↗
PubMed1999

Muscle fiber-type changes induced by botulinum toxin injection in the rat larynx.

This study examined muscle fiber-type alterations after single or multiple botulinum toxin (BT) injections to better understand possible morphologic changes induced by therapeutic BT injections in patients with spasmodic dysphonia. Muscle fiber staining was accomplished in rat intrinsic laryngeal muscles with antibodies to specific myosin heavy chains. Results indicated that the typical baseline distributions of type II muscle fibers (ie, types IIa, IIb, IIx, and IIL) were altered by BT injection, while no change was observed in type I fibers. Embryonic fibers were observed only along the needle insertion site at 7 days post BT injection. Although inferences from these animal data to human neuromuscular function must be made with caution, our findings provide insight into the possible cellular and molecular changes characterizing BT-injected muscles.

Animals↗
PubMed1999

Advances and refinements in phonosurgery.

Scientific discovery, technological advances, and improved outcomes assessment have resulted in advances and refinements in phonosurgery. Three areas of substantial evolution are phonomicrosurgery, laryngeal framework surgery, and the use of implantable materials in vocal folds. Discovery of the importance of the superficial layers of the lamina propria has led to increased use of more limited medial microflap approaches and less frequent use of the classic lateral cordotomy flap approach. Alternative approaches to managing vocal fold scarring defects have addressed the separation of body and cover and provided suitable lamina propria replacement. Approaches to sulcus vocalis have been refined to address type II (linear vergeture) and type III (focal invasive pit) sulcus, where there is loss of lamina propria, while still recognizing the common nonpathological type I (physiological) sulcus. Technological advancements such as photodynamic therapy, tuned dye lasers, and laryngeal microdebridement have augmented the armamentarium for mechanical removal of laryngeal papillomata. Careful infusion-assisted microexcision and adjunctive medical management have been refined and made more effective. Laryngeal framework surgery has embraced the development of Silastic, hydroxylapatite, expanded polytetrafluoroethylene, and titanium shims. Anatomical studies have helped to improve operative precision and safety, and have led to inventive variations in arytenoid repositioning that improve closure of the posterior subunit. Vocal fold augmentation by injection has been facilitated by innovative use of the rigid telescope and intraoperative videostroboscopy. Anatomical studies have focused on the infrafold region and rheological studies have attempted to match viscoelastic properties of injectable substances to those of vocal fold tissues. Alloplastic materials such as Teflon have been largely supplanted by newer bioimplantables such as fat, collagen, and fascia.

Endoscopy↗
PubMed1998

Planned postradiotherapy neck dissection in patients with advanced head and neck cancer.

BACKGROUND: Metastatic neck nodes in patients with squamous cell carcinoma of the head and neck are most commonly managed by surgery, radiotherapy, or combined-modality therapy. For combined-modality cases, the sequencing of surgery and radiotherapy is generally guided by which modality is considered preferable for treatment of the primary tumor. A postradiotherapy neck dissection is often considered for those patients with > N1 disease in which the primary is treated with radiotherapy alone. METHODS: Between February 1991 and October 1995, 25 patients with node-positive squamous cell carcinoma of the head and neck were treated with planned unilateral (n = 22) or bilateral (n = 3) neck dissection following high-dose radiotherapy. The primary tumor sites included: tongue base (n = 11), tonsil (n = 6), nasopharynx (n = 3), pyriform sinus (n = 2), supraglottic larynx, (n = 1), soft palate (n = 1), and unknown head and neck primary (n = 1). The specific nodal stage breakdown of the 28 individual neck dissections (25 patients) was N1 (n = 1), N2A (n = 5), N2B (n = 15), N3 (n = 7). RESULTS: Nineteen of the 28 neck dissections (68%) demonstrated no evidence of residual carcinoma. Of the nine positive neck dissections, six revealed malignant cells in a single nodal echelon. The 1- and 2-year rate of neck control in all 25 patients was 100% and 93%, respectively. The 1- and 2-year disease-specific survival for all 25 patients was 83% and 60%, respectively. With a minimum follow-up of 2 years, 64% of the 25 patients remain alive with no evidence of disease or dead of non-cancer causes. CONCLUSION: In this series of postradiotherapy neck dissections, two thirds of the dissections demonstrated no evidence of residual tumor (19/28, or 68%). However, there was not a direct correlation between pretreatment nodal size (neck staging), radiation dose delivered, and the likelihood of achieving a cancer-free neck dissection. Only one of 28 postradiotherapy neck dissections identified tumor outside of nodal stations II-IV. The predictable pattern of residual disease in pathologically positive cases suggests that a selective neck dissection encompassing levels II-IV may be appropriate in a majority of patients.

Adult↗
PubMed1998

Influence of computed tomography on pretherapeutic tumor staging in head and neck cancer patients.

Refinements in radiographic techniques have resulted in increased use of radiographic studies in the evaluation of patients with head and neck cancer over the past 20 years. To assess the impact of such studies, we compared tumor clinical stages based solely on physical-examination findings with those obtained with the addition of CT findings. This study was accomplished through case review of 81 head and neck cancer patients who underwent CT after preliminary TNM-stage assignment as determined on the basis of physical examination alone. In this cohort, 44 patients (54%) had a change in assigned clinical stage. We reviewed individual anatomic sites to determine where CT was found to be most useful in modifying tumor stage. Changes in tumor and nodal stage were found across all major sites of the head and neck. Tumors of the hypopharynx were the most likely to change stage (90%) on the basis of CT findings, whereas tumors of the glottic larynx were least likely to undergo a change in stage (16%). The therapeutic implications of these findings are discussed in the context of the published literature.

Head and Neck Neoplasms↗
PubMed1998

An anatomic study of the rat larynx: establishing the rat model for neuromuscular function.

The gross and microscopic anatomy of the rat larynx was studied with particular attention to myology and neuromuscular structures to further validate it as a model to evaluate morphologic and functional changes induced by botulinum injection. A laryngeal alar cartilage (LAIC), alar cricoarytenoid (ACA) muscle, and a superior cricoarytenoid muscle (SCA) were identified as anatomic structures not previously described. Two portions (medial and lateral) of the thyroarytenoid muscle (TA) were distinguished. The function of the ACA was suggested to be similar to the aryepiglottis muscle in humans and the function of the SCA was suggested to be similar to the human interarytenoid muscle. The predominant pattern of motor endplate (MEP) distribution in rat laryngeal muscles (posterior cricoarytenoid, lateral cricoarytenoid, cricothyroid, and SCA) was to have MEPs concentrated mostly at the midbelly of muscle where they were distributed throughout the cross-sectional area of the midbelly. The TA and ACA differed from this pattern. The lateral TA had MEPs concentrated at the anterior third of its belly and those of the medial TA were located at the midbelly. Motor endplates in the ACA were located mostly at the posterior portion of muscle. Muscle fiber-typing showed subtle differences between the intrinsic laryngeal muscles. Fast fibers were predominant in the rat laryngeal muscles. This study supports the expanded use of rats in studies of laryngeal neuromuscular function and disease in humans.

Animals↗
PubMed1998

The histologic fate of autologous collagen injected into the canine vocal fold.

Collagen is a functionally essential component of the five-layered structure of the vocal fold. Soluble bovine collagen has previously been shown to be an effective injectable bioimplant for vocal fold defects, paralysis, and, especially, scarred larynges. Although bovine collagen appears to be well tolerated, the concern for possible adverse immunologic responses has deterred approval from the Food and Drug Administration for its clinical use in the larynx. Currently we are investigating the use of injectable autologous collagen for vocal fold augmentation. The purpose of this study is to examine the histologic fate of autologous collagen injected into the canine vocal fold at multiple intervals after injection. An ellipse of skin measuring 3 x 6 cm was harvested from each of three dogs and processed into a naturally cross-linked injectable solution of collagen (Autologen). This autologous collagen was injected into one vocal fold and a control injection of buffer solution was injected contralaterally. The injections were well tolerated and no dog appeared to suffer any immediate or delayed ill effects. The dog larynges were harvested 1, 3, and 6 months after collagen injection and examined grossly and histologically. Injected autologous collagen material persisted in these experimental animals and appeared to be well tolerated. Based on this preliminary study, we anticipate autologous collagen to be at least as suitable as bovine chemically cross-linked collagen as an injectable bioimplant for vocal fold augmentation. It may also have the advantage of added safety and stability.

Animals↗
PubMed1998

Physiologic assessment of botulinum toxin effects in the rat larynx.

OBJECTIVE: Botulinum toxin (BT) is a currently used treatment for spasmodic dysphonia (SD) and other related focal dystonias. The goal of this study is to provide a basis for using the rat larynx to objectively assess physiological and histological effects of BT. STUDY DESIGN: Dosages and volumes of BT injection were varied and three physiological parameters were measured. These measures included: optical density of PAS-stained laryngeal muscle after electrical stimulation, which is an indirect measure of denervation, spontaneous laryngeal muscle activity, and laryngeal movement. METHODS: A new microlaryngoscopic technique was developed, which made it possible to observe and manipulate the rat larynx endoscopically. Laryngeal movement and electromyographic (EMG) measures were made prior to injection and 3 days following BT injections of various dosages and volumes. Optical density measures were made 3 days after injection. RESULTS: Significant reductions in vocal fold motion and spontaneous laryngeal muscle activity as a function of increased BT dosage were observed. In addition, the optical density of PAS-stained laryngeal muscle after electrical stimulation was increased following BT injection. Significant volume effects in optical density were observed in the lateral thyroarytenoid and lateral cricoarytenoid muscles on the contralateral side. CONCLUSIONS: The rat laryngeal model is suitable for assessing BT effects. In addition, the three physiological variables provided useful and reliable measures of laryngeal function. It is the authors' intention to use the rat laryngeal model to further examine the physiological and histological effects of BT with the goal of developing new methods for the treatment of patients with SD and other focal dystonias.

Animals↗
PubMed1998

Increased acute and chronic mitotic activity in rat laryngeal muscles after botulinum toxin injection.

OBJECTIVES: To characterize the acute and chronic cellular effects of botulinum toxin (BT) injection into rat laryngeal muscles. A complete characterization of these effects is important because patients with focal dystonias of the head and neck are commonly treated with BT injection. Further, potential muscular changes in the larynx must be carefully delineated owing to the critical phonatory and airway protective functions of these muscles. STUDY DESIGN: The acute and chronic cellular effects of BT injection were studied using 5'-bromo 2'-deoxyuridine (BrdU) following single and repeated BT injection into rat laryngeal muscles. BrdU is incorporated into mitotically active nuclei such that changes in cell proliferative behavior following BT injection can be monitored. RESULTS: Increased mitotic activity was detected in the tissue samples studied following BT injection. Differences in the times of the peak distribution of BrdU-labeled cells in each laryngeal muscle were observed. This may be related to the diffusion effects of BT. Prolonged muscle fiber changes, including splitting, were also observed as the result of repeated BT injection. CONCLUSIONS: The results of this study suggest that BT may induce a proliferative response in muscle tissue.

Animals↗
PubMed1997

Manual circumlaryngeal therapy for functional dysphonia: an evaluation of short- and long-term treatment outcomes.

Manual circumlaryngeal therapy (manual laryngeal musculoskeletal tension reduction) was used to treat 25 consecutive functional dysphonia patients. Pre- and post-treatment audio recordings of connected speech and sustained vowel samples were submitted to auditory-perceptual and acoustical analysis to assess the immediate and long-term effects of a single treatment session. To complement audio recordings, subjects were interviewed in follow-up regarding the stability of treatment effects. Pre- and post-treatment comparisons demonstrated significant voice improvements. No significant differences were observed between post-treatment measures, suggesting that vocal gains were maintained. Interviews revealed 68% of subjects reported occasional partial recurrences, typically less than 4 days in duration, which resolved spontaneously. These results replicate and extend previous research suggesting the utility of manual circumlaryngeal therapy for functional voice disorders.

Adult↗
PubMed1997

Psychological correlates of functional dysphonia: an investigation using the Minnesota Multiphasic Personality Inventory.

Abnormal psychological factors have been implicated in the development of functional dysphonia (FD). This investigation describes the personality and psychological characteristics of 25 female subjects who had received the diagnosis of FD. In all subjects symptoms were resolved after voice therapy. While vocally asymptomatic, these remitted subjects with FD completed the Minnesota Multiphasic Personality Inventory (MMPI), an objective personality questionnaire. When compared with a medical outpatient control group, the results showed that subjects with FD scored significantly higher on 7 of 10 clinical scales, suggesting an elevated degree of emotional maladjustment. A stepwise logistic discriminant analysis identified 2 clinical scales that provided valuable discriminatory power between the two groups. Scale 1 (Hs-hypochondriasis), which measures the number and type of reported somatic complaints, and scale 7 (Pt-psychasthenia), a measure of diffuse anxiety, discriminated the groups with 88% sensitivity and 89% specificity. The results suggested that in spite of symptom improvement after voice therapy, the subjects with FD continued to exhibit poor levels of adaptive functioning, which may represent trait-like vulnerability. The clinical implications of these results for voice practitioners are discussed.

Adolescent↗
PubMed1997

Correlation between vocal functions and glottal measurements in patients with unilateral vocal fold paralysis.

Observations and analysis of glottal characteristics are critical in choosing the best modality for surgery in patients with unilateral vocal fold paralysis (UVP). This study suggests that multiple glottal characteristics influence the vocal product in patients with UVP. In addition to the horizontal position of the paralyzed vocal fold (deviation from the midline), the glottal area, degree of bowing of the paralyzed and contralateral vocal folds, maximum separation between vocal folds, compensatory glottal maneuvers, and the vertical glottic closure plane significantly influenced the quality of the voice. Clinicians should be aware of these observations to facilitate treatment planning and assessment of the results of surgical procedures used to improve voice quality in cases of UVP.

Adult↗
PubMed1997

Transoral electromyographic recordings in botulinum toxin-injected rat larynges.

Objective assessment of muscle function following botulinum toxin injections in laryngeal muscles is difficult in human subjects. We developed a rat laryngeal model for the study of botulinum toxin injection. A new laryngoscopic technique has made it possible to observe the rat larynx endoscopically and to obtain electromyographic measurements during and after injection of toxin. The electromyographic interference pattern, fibrillation potentials, and vocal fold movement were used for analyzing dose and volume effects of injected toxin. We conclude that the lowest dosage able to produce the maximal duration of functional laryngeal impairment is 0.07 U in a volume of 0.4 microL. This model will enable us to obtain physiologic and histologic parameters that can be used to assess the selection of optimal treatment regimens with botulinum toxin for the treatment of patients with spasmodic dysphonia.

Animals↗
PubMed1997

Efficacy of repeated botulinum toxin injections as a function of timing.

This pilot study was designed to determine if the interval between repeated botulinum toxin injections influenced physiologic and histologic effects on laryngeal muscles in a rat model. The physiologic measurements included digitized videomicroscopic recording of vocal fold movement and electromyography. The histologic measurements included muscle fiber size and digitized optical density of laryngeal muscles after glycogen depletion by electrical stimulation. The results demonstrated that the effect of timing of the second injection was strongly correlated to laryngeal changes. Most notable were results in the subjects that underwent injections 6 weeks apart. We hypothesize that these findings might be related to terminal axonal sprouting with reinnervation. The results from this study help confirm and expand the validity of using the rat laryngeal model to understand the effect of botulinum toxin. Moreover, we believe that the data might be extrapolated to prove useful in predicting human responses to botulinum toxin treatment for functional dystonias such as spasmodic dysphonia.

Animals↗
PubMed1996

Analysis of factors affecting botulinum toxin results in spasmodic dysphonia.

This study was designed to investigate how variations in patterns of injection could improve the efficacy of botulinum toxin injections in relieving the symptoms of adductor spasmodic dysphonia. A total of 64 adductor spasmodic dysphonia patients who were injected using indirect laryngoscopic localization (for a total of 426 injections) were analyzed retrospectively using their own subjective data on duration of voice improvement, optimal voice improvement, breathiness side effects, and intervals between treatments. Injection to both the thyroarytenoid (TA) and the lateral cricoarytenoid (LCA) simultaneously gave the best voice results; the overall improvement from baseline was the longest lasting, and the period during which the voice was the best was the longest lasting. TA+LCA also gave the shortest duration of undesirable breathiness side effect. On the basis of these data, it seems reasonable to recommend that initial botulinum toxin therapy for adductor spasmodic dysphonia patients should be a single unilateral injection placed strategically at the posterior portion of the TA and directed toward the LCA so that both muscle groups are affected.

Adult↗
PubMed1996

Sulcus vocalis: a rational analytical approach to diagnosis and management.

The term sulcus vocalis has been applied to a spectrum of disorders ranging from minor vocal fold indentations to destructive lesions causing severe dysphonia. To clarify the pathophysiology and to develop a more rational approach to treatment, we report a series of sulcus patients including 20 surgical cases. Clinical and histopathologic analysis produced a clinically useful classification: type 1 is a physiologic variant accentuated by atrophy but with intact lamina propria; types 2 (sulcus vergeture) and 3 (sulcus vocalis) are characterized by severe dysphonia, loss of vibratory activity, and destruction of the functional superficial lamina propria. These latter cases respond favorably to microsurgery designed to remove destroyed tissue, release scar contracture, and promote mucosal redraping by regional undermining. Further study of the extracellular matrix of the superficial lamina propria (Reinke's space) might indicate a common pathway in the pathogenesis of sulcus deformities and other related benign vocal fold lesions.

Adult↗