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Biomedical subjects

Steven M Zeitels

Publications and source records attributed to Steven M Zeitels.

At least 19 recordsLinked to original sources

Effects of 532 nm pulsed-KTP laser parameters on vessel ablation in the avian chorioallantoic membrane: implications for vocal fold mucosa.

OBJECTIVES: Selective vascular ablation (photoangiolysis) using pulsed lasers that target hemoglobin is an effective treatment strategy for many vocal fold lesions. However, vessel rupture with extravasation of blood reduces selectivity for vessels, which is frequently observed with the 0.45-ms, 585-nm pulsed dye laser. Previous studies have shown that vessel rupture is the result of vaporization of blood, an event that varies with laser pulse width and pulse fluence (energy per unit area). Clinical observations using a 532-nm wavelength pulsed potassium-titanyl-phosphate (KTP) laser revealed less laser-induced hemorrhage than the pulsed dye laser. This study investigated settings for the pulsed KTP laser to achieve selective vessel destruction without rupture using the avian chorioallantoic membrane under conditions similar to flexible laryngoscopic delivery of the laser in clinical practice. STUDY DESIGN: The chick chorioallantoic membrane offers convenient access to many small blood vessels similar in size to those targeted in human vocal fold. Using a 532-nm pulsed KTP laser, pulse width, pulse energy, and working distance from the optical delivery fiber were varied to assess influence on the ability to achieve vessel coagulation without vessel wall rupture. METHODS: Third-order vessels (n = 135) were irradiated: Energy (471-550 mJ), pulse width (10, 15, 30 ms), and fiber-to-tissue distance (1 mm, 3 mm) were varied systematically. RESULTS: Selective vessel destruction without vessel wall rupture was more often achieved by increasing pulse width, increasing the fiber-to-tissue distance, and decreasing energy. Vessel destruction without rupture was consistently achieved using 15- or 30-ms pulses with a fiber-to-tissue distance of 3 mm (pulse fluence of 13-16 J/cm). CONCLUSIONS: This study substantiates our clinical observation that a 532-nm pulsed KTP laser was effective for ablating microcirculation while minimizing vessel wall rupture and hemorrhage.

Animals↗

The evaluation of benign glottic lesions: rigid telescopic stroboscopy versus suspension microlaryngoscopy.

Rigid telescopic strobo-video-laryngoscopy (RTS) is a primary clinical assessment methodology in the office evaluation of benign glottic lesions. However, diagnostic observations can be made only at the time of suspension microlaryngoscopy (SML). The records of 100 consecutive patients undergoing microlaryngoscopy for benign glottic lesions were retrospectively reviewed. Nine of 100 patients were found to have additional glottic lesions during SML. Sixteen additional lesions were noted in these nine patients. Fifteen of 16 lesions were sulci and/or mucosal bridges. Forty-five percent (4/9) of the patients with additional lesions underwent a management change intraoperatively. Three patients underwent additional surgical dissection, and one underwent less dissection than was planned. The discrepancy in diagnosis between rigid telescopic strobo-video-laryngoscopy and suspension microlaryngoscopy highlights certain key points: (1) During office endoscopy, tangential views of the medial surface of the glottis limit the diagnostic sensitivity. (2) Sulci and mucosal bridges are most subject to this limitation. (3) Informed consent should address the potential need for a change in intraoperative management. It is advisable to discuss the possibility for dissection in both vocal folds, even if a unilateral lesion is observed in the office. (4) Microlaryngoscopy is the final diagnostic step in the evaluation of glottic pathology. Meticulous inspection and palpation of the glottis are recommended during SML.

Adult↗

Recurrent laryngeal nerve injuries after esophagectomy.

Unilateral vocal-cord paralysis after esophagectomy involving a cervical anastomosis is uncommon in experienced hands but can cause marked morbidity because of pulmonary complications. It is important for the surgeon to understand the anatomy of the recurrent laryngeal nerve to avoid this complication. The diagnosis is usually easily made at the bedside and can be confirmed by visualization of the glottis. Early treatment may include supportive care with a speech pathologist or injection of the vocal-cord with temporary material to improve glottic closure. Definitive treatment can best be performed by medialization thyroplasty.

Esophagectomy↗

Hyaluronic acid-based microgels and microgel networks for vocal fold regeneration.

Vocal fold scarring disrupts the viscoelastic properties of the lamina propria that are critical for normal phonation. There is a clinical need for the development of advanced biomaterials that approximate the mechanical properties of the lamina propria for in vivo vocal fold regeneration. We have developed hyaluronic acid (HA)-based microgels and cross-linked microgel networks with tunable degradation and mechanical properties. HA microgels were prepared by cross-linking HA derivatives carrying hydrazide (HAADH) and aldehyde (HAALD) functionalities within the inverse emulsion droplets. Alternatively, poly(ethylene glycol) dialdehyde (PEGDiALD) was employed in place of HAALD. Microgels based on HAADH/HAALD are more resistant to enzymatic degradation than those generated from HAADH/PEGDiALD. In vitro cytotoxicity studies using vocal fold fibroblasts indicate that microgels synthesized from HAADH/HAALD are essentially nontoxic, whereas microgels derived from HAADH/PEGDiALD exhibit certain adverse effects on the cultured cells at high concentration (> or =2 mg/mL). These microgels exhibit residual functional groups that can be used as reactive handles for covalent conjugation of therapeutic molecules. The presence of residual functional groups also allows for subsequent cross-linking of the microgels with other reactive polymers, giving rise to doubly cross-linked networks (DXNs) with tunable viscoelasticity. Mechanical measurements using a torsional wave apparatus indicate that HA-based DXNs exhibit elastic moduli that are similar to those of vocal fold lamina propria at frequencies close to the range of human phonation. These HA-based microgel systems are promising candidates for the treatment of vocal fold scarring, not just as biocompatible filler materials, but as smart entities that can repair focal defects, smooth the vocal fold margin, and potentially soften and dissolve scar tissue.

Aldehydes↗

Measurements of vocal fold elasticity using the linear skin rheometer.

OBJECTIVE: The linear skin rheometer (LSR), which measures skin visco-elasticity, was adapted for measurements of vocal fold properties. A series of studies was performed on animal and human excised larynges to determine if the LSR technique can be applied to the vocal fold. METHODS: In excised larynges, small patches of mucosa were driven sinusoidally at 0.3 Hz over distances of 1-2 mm using a small probe. Forces in the order of 1 g equivalent gave optimal measurements. Stiffness and viscosity values were derived from stress/strain data. RESULTS: The instrument was able to measure the visco-elasticity of the tissue in a repeatable manner and it could detect areas where the tissue was artificially stiffened. Two-dimensional maps of the mechanical properties of the laryngeal mucosa were obtained showing local variations in elasticity both parallel and perpendicular to the vocal fold edge. Initial studies were undertaken using animal tissue; more recently, the LSR has been successfully used to obtain similar data from human tissue. CONCLUSION: The LSR was been demonstrated to be capable of measuring the elastic properties of the vocal fold in a repeatable and reliable manner. Further studies will now be undertaken to obtain data from a larger sample of human tissue.

Animals↗

Quantitative and comparative studies of the vocal fold extracellular matrix. I: Elastic fibers and hyaluronic acid.

OBJECTIVES: This study examines the elastic fiber and hyaluronic acid (HA) content of the midmembranous vocal fold laminae propriae (LPs) of humans, dogs, pigs, and ferrets. METHODS: Lamina propria elastin was quantified by measuring the amino acid desmosine, and HA was measured by an enzyme-linked immunosorbent assay-based technique. Quantitative histology was used to evaluate elastin and HA levels in specific LP regions. The distributions of fibrillin-1, a primary microfibrillar component of elastic fibers, and of tropoelastin, an indicator of elastin synthesis, were immunohistochemically analyzed. RESULTS: Elastin and HA constituted 8.5% +/- 2.1% and 0.82% +/- 0.11% of human LP, respectively, relative to tissue total protein. Although the mean LP desmosine levels were similar across species, the mean HA levels in canine (p < 3.1 x 10(-5)), porcine (p < 1.5 x 10(-5)), and ferret (p < 6.6 x 10(-4)) LPs were 3 to 4 times higher than that in humans. Marked interspecies differences in elastin, fibrillin-1, tropoelastin, and HA distributions were observed histologically. CONCLUSIONS: The elastin content of the human LP is roughly twice that of the dermis, whereas the HA content of the human LP is similar to that of the dermis. Although all species had similar levels of desmosine, histologic evaluation indicates that the porcine elastin distribution is most similar to that of the human LP. Fibrillin-1 staining suggests that stress in the human LP may be particularly high in the superior superficial layer, and tropoelastin staining indicates that the rate of LP elastin turnover may vary spatially.

Animals↗

Quantitative and comparative studies of the vocal fold extracellular matrix II: collagen.

OBJECTIVES: This study examines the collagen content and turnover in the midmembranous vocal fold laminae propriae (LPs) of humans, dogs, pigs, and ferrets. METHODS: The LP collagen levels were assessed by quantifying tissue hydroxyproline. Quantitative histology allowed evaluation of the collagen content in specific LP regions. Several collagen types and two markers of collagen turnover were examined immunohistochemically. RESULTS: Collagen made up 43.4% +/- 2.6% of human LP total protein (TP), with men having approximately 30% higher collagen content than women (p < .024). The collagen levels in pigs (52.6% +/- 1.9% of TP) and ferrets (29.8% +/- 3.7% of TP), but not that in dogs (45.3% +/- 1.2% of TP), varied significantly from that in humans (pigs, p < .016; ferrets, p < .011). Quantitative histology indicated marked interspecies differences in total collagen distribution. Collagen types I, III, and IV were detected in the LP, and spatially complex staining patterns were observed for the two markers of collagen turnover studied. CONCLUSIONS: The collagen content of the human LP is approximately 60% to 70% of that of human dermis. Although canine LP collagen levels are most similar to those of humans, quantitative histology indicates that the collagen distribution of the human LP is best matched by the porcine LP. Collagen types I and III seem to be the dominant LP collagens. Spatial variations in collagen turnover appear to exist that may contribute to normal LP physiology.

Animals↗

Imaging the human vocal folds in vivo with optical coherence tomography: a preliminary experience.

OBJECTIVES: Optical coherence tomography (OCT) and polarization-sensitive OCT (PS-OCT) are promising noninvasive methods for in vivo, cross-sectional imaging of the microstructure of the vocal folds. Previous studies in other tissues have shown an axial resolution of less than 10 microm and a maximum imaging depth of about 2 mm. The objectives of this pilot study were to obtain images from the vocal folds of subjects who were being evaluated and/or treated for vocal fold disease and to evaluate how well normal and pathologic microstructure could be seen in these images. METHODS: Twenty-six vocal folds in 13 subjects were imaged with a flexible OCT probe. The images were successfully collected from subjects who were either topically anesthetized or under general anesthesia for microlaryngoscopic procedures. RESULTS: The thickness of the epithelium, the relative collagen content of the subepithelial connective tissue, and certain characteristic features of lesions (including cysts, scarring, and papilloma) were seen in the OCT and PS-OCT images. CONCLUSIONS: "Live microscopy" of the human vocal folds is very promising for improved diagnosis, mapping, and treatment planning. To our knowledge, this study is the first application of PS-OCT for in vivo imaging of the human vocal folds.

Humans↗

Carbon dioxide laser fiber for laryngeal cancer surgery.

OBJECTIVES: The carbon dioxide laser has evolved to be the premier dissecting instrument for hemostatic cutting during endolaryngeal cancer resection. However, dissection is limited to mirror-reflected line-of-sight delivery of the laser. A recently developed flexible, hollow photonic bandgap fiber (PBF) appears to offer advantages in endolaryngeal dissection. METHODS: The suitability of the PBF for human application was evaluated in a canine experiment in which human surgical procedures for microlaryngoscopic en bloc partial laryngectomy were simulated. The specimens that were resected endoscopically and the completion laryngectomy specimen were evaluated histologically. RESULTS: Observations from this experiment revealed that en bloc partial laryngectomy procedures were substantially easier to achieve as compared with prior experience in humans. This improvement resulted from three factors: 1) enhanced tangential dissection due to increased angulation of the laser energy, 2) enhanced procedural orientation due to proprioception of the tissues in contact mode, and 3) improved hemostasis. Histopathologic analysis of the resection margins revealed minimal thermal trauma. CONCLUSIONS: The PBF shows substantial promise for human application in endoscopic partial laryngectomy. It will likely enhance the ability of any surgeon to extend his or her indications for performing endoscopic laryngeal cancer resections regardless of philosophy (en bloc resection or piecemeal).

Animals↗

Pulsed angiolytic laser treatment of ectasias and varices in singers.

OBJECTIVES: Varices and ectasias in singers are typically the result of phonotraumatic shearing stresses and/or collision forces on the microcirculation within the superficial lamina propria. These lesions can be debilitating in performing vocalists because of the effect of recurrent hemorrhage and/or as a contributing factor to the morbidity of other mass lesions such as polyps, nodules, and cysts. Phonomicrosurgical treatment of performers is understandably approached with great trepidation, as the vocal liability of surgically disturbing the superficial lamina propria and epithelium must be balanced with the inherent detrimental vocal effect(s) of the lesion(s). Pulsed angiolytic lasers that emit radiation at high absorbance peaks of oxyhemoglobin were examined to determine whether they were an efficacious treatment approach for ectasias and varices based on these lasers' mechanisms of action and prior experience in phonomicrosurgery. METHODS: A prospective trial was done in 39 patients (40 procedures in 54 vocal folds) without complication to evaluate the effectiveness of a 585-nm pulsed dye laser (PDL; 25 cases) and a 532-nm pulsed KTP laser (15 cases) in a noncontact mode to treat 65 varices and 43 ectasias. Twenty-nine of 39 patients had varices and ectasias associated with other phonotraumatic mass lesions that required resection. RESULTS: All patients have resumed full vocal activities, and no patient has had a subsequent hemorrhage or vocal deterioration. CONCLUSIONS: Both the 585-nm PDL and the 532-nm pulsed KTP laser were found to be efficacious and relatively safe treatment modalities for vascular abnormalities of the vocal folds in singers. Noncontact selective photoangiolysis of the aberrant vessels prevented future bleeding without substantial photothermal trauma to the overlying epithelium and surrounding delicate superficial lamina propria, thereby allowing for optimal postoperative mucosal pliability and glottal sound production. However, the pulsed KTP laser was substantially easier to use because of its enhanced hemostasis due to its longer pulse width. Vessel wall rupture was commonplace during use of the 585-nm PDL, but rarely occurred during photoangiolysis with the 532-nm pulsed KTP laser.

Dilatation, Pathologic↗

Office-based 532-nm pulsed KTP laser treatment of glottal papillomatosis and dysplasia.

OBJECTIVES: Treatment of glottal papillomatosis and dysplasia was mirror-guided and done in surgeons' offices in the 19th century. It migrated to the operating room in the 20th century to accommodate direct laryngoscopic surgery, which required assistants to administer anesthesia and procedural support. The primary treatment goals, which are disease regression and voice restoration and/or maintenance, are tempered by the morbidity of general anesthesia and potential treatment-induced vocal deterioration. To obviate general anesthesia, office-based laser laryngeal surgery was first done in 2001 with the 585-nm pulsed dye laser (PDL), because it employs a fiber delivery system and its energy is selectively absorbed by oxyhemoglobin. Since then, this new angiolytic laser treatment paradigm has become a mainstay of management for many surgeons; however, there are a number of shortcomings of the PDL. To further develop this concept and address the limitations of the PDL, we used a 532-nm pulsed potassium titanyl phosphate (KTP) laser. METHODS: A prospective assessment was performed on 48 patients in 72 cases of recurrent glottal dysplasia (36) or papillomatosis (36). All individuals had previously undergone microlaryngoscopic management with histopathologic evaluation. RESULTS: Two dysplasia patients did not tolerate the procedure. Of the treatable dysplasia cases, there was follow-up in 29 of 34. Disease regression was at least 75% in 18 of 29 cases (62%), 50% to 75% in 7 of 29 (24%), and 25% to 50% in the remaining 4 of 29 (14%). Papilloma patients returned for treatment when symptoms recurred, so disease regression could not be assessed accurately. Similar to data obtained with the PDL, these data confirmed that dysplastic mucosa could normalize without resection. CONCLUSIONS: Our observations revealed that the 532-nm pulsed KTP laser provided enhanced performance over the PDL laser in a number of ways. The ability to use smaller glass fibers precluded mechanical trauma to the channels of the flexible laryngoscopes and allowed for improved suctioning of secretions. Oxyhemoglobin absorbs energy better at 532 nm than at 585 nm, and the KTP laser can be delivered through a longer pulse width. These factors provide enhanced hemostasis and improved intralesional energy absorbance. Finally, unlike the PDL, the KTP laser is a solid-state laser and is not prone to mechanical failure.

Ambulatory Surgical Procedures↗

Comparison of a flexible laryngoscope with calibrated sizing function to intraoperative measurements.

OBJECTIVES: The objectives were to assess the clinical performance and accuracy of a prototype fiberoptic transnasal laryngeal endoscope with an auxiliary optical system that allows images to be spatially calibrated. METHODS: A novel fiberoptic endoscope was developed that projects green laser beams across the field of view from a separate optical channel. According to the location of the spots in the field of view, the images can be calibrated with a software routine. To assess its performance, we compared measurements of 14 lesions imaged with the calibrated endoscope and during microlaryngoscopy, where a calibration instrument was placed next to the lesions. Four clinicians measured lesion length, width, and area from the collected images. RESULTS: The calibrated endoscope performed as well as current flexible fiberoptic laryngoscopes in terms of image quality and patient comfort. For lesions with well-defined borders, the error ranged from 14% to 23% for length, from 20% to 30% for width, and from 33% to 50% for area across observers. Factors contributing to larger errors in some subjects were identified. CONCLUSIONS: The calibrated endoscope is capable of providing useful sizing information for laryngeal structures, and these measures correspond quite well to more direct measurements in the operating room. Objective sizing of laryngeal lesions is complicated by subjective judgments of lesion boundaries, which can be indistinct in many cases.

Adult↗

Ambulatory monitoring of disordered voices.

OBJECTIVES: Recently developed systems for ambulatory monitoring of voice use employ miniature accelerometers placed at the base of the anterior neck to sense phonation. As it is hoped that such systems will help improve the clinical assessment and management of voice disorders, this study was undertaken to determine the impact of dysphonia severity on the accuracy of accelerometer-based estimates of vocal function. METHODS: Simultaneous recordings were made of oral acoustic (microphone) and neck skin acceleration signals for 6 normal speakers and 18 patients with voice disorders (mild to severe dysphonia) as they performed several speech tasks. Measures of phonation time, fundamental frequency, and sound pressure level were extracted from the two types of signals and compared. RESULTS: It was generally demonstrated that accelerometer-based measures closely approximated corresponding measurements obtained from a microphone signal across all levels of dysphonia severity. Furthermore, there was evidence that in some cases the accelerometer may actually represent a more robust approach for estimating phonation parameters in disordered voices. CONCLUSIONS: The results generally support the recent application of accelerometers as phonation sensors in ambulatory voice monitoring systems that can be used in the clinical assessment and management of voice disorders.

Adult↗

Office-based and microlaryngeal applications of a fiber-based thulium laser.

OBJECTIVES: The carbon dioxide (CO2) laser is the premier dissecting instrument for hemostatic cutting and ablation during endolaryngeal surgery. However, microlaryngeal tangential dissection and office-based photoablation have been limited by the lack of a fiber-based delivery system. To address this limitation, a new laser was designed, which is a diode-pumped solid-state laser with a thulium-doped yttrium-aluminum-garnet laser rod. It produces a continuous-wave beam with a wavelength of 2013 nm and a target chromophore of water. This new laser functions similarly to a CO2 laser with the benefit of being delivered through a small glass fiber (0.365 to 0.550 mm). METHODS: A prospective pilot trial was done in 74 cases to explore applications of the new thulium laser. Thirty-two procedures were done with the laser used as an ablating instrument and topical anesthesia through a flexible laryngoscope (papillomatosis, 20; microinvasive carcinoma, 6; benign supraglottic lesions, 3; edema, 2; granuloma, (1). Forty-two procedures were done with the laser used as a cutting or ablating instrument for microlaryngeal dissection and general anesthesia. These included 27 partial laryngeal resections (supraglottis, 15; glottis, 10; subglottis, (2) and 8 posterior glottic laryngoplasties. The laser was also used as an ablative instrument during microlaryngoscopy in 7 cases. RESULTS: The thulium laser was used effectively in all cases, under both local and general anesthesia. In microlaryngeal dissection, electrocautery was not needed to control bleeding, even during cutting in the highly vascular paraglottic space. No complications related to the use of the thulium laser were experienced in any case. CONCLUSIONS: Because of the fiber-based delivery system, the 2013-nm continuous-wave thulium laser shows substantial promise for tangential dissection during microlaryngoscopy and soft tissue photoablation during office-based flexible laryngoscopy. Hemostasis was judged to be superior to experiences with the CO2 laser. In this pilot study, performing en bloc laryngeal cancer resection procedures was facilitated by use of the thulium laser.

Adult↗

Collagen composite hydrogels for vocal fold lamina propria restoration.

Chronic voice impairment due to scarring of the vocal fold (VF) lamina propria (LP) can be debilitating in terms of quality of life. Due to the dependence of normal VF vibration on proper VF geometry, an implant inserted to restore appropriate shape and pliability to scarred LP should ideally maintain its insertion-dimensions while being replaced by newly synthesized extracellular matrix (ECM). In the present study, collagen-alginate and collagen-hyaluronan (HA) composite hydrogels were investigated for their ability to support ECM synthesis by VF fibroblasts with limited hydrogel compaction and/or resorption. Collagen-HA composites showed significant mass loss over 28 days of culture, with little evidence of new matrix production. Collagen-alginate composites, in contrast, resisted scaffold compaction and mass loss for at least 42 days in culture while allowing for ECM synthesis. Collagen-alginate hydrogels appear to be promising materials for VF restoration, warranting further investigation.

Alginates↗

Measurement of vocal fold collision forces during phonation: methods and preliminary data.

Forces applied to vocal fold tissue as the vocal folds collide may cause tissue injury that manifests as benign organic lesions. A novel method for measuring this quantity in humans in vivo uses a low-profile force sensor that extends along the length and depth of the glottis. Sensor design facilitates its placement and stabilization so that phonation can be initiated and maintained while it is in place, with minimal interference in vocal fold vibration. In 2 individuals with 1 vibrating vocal fold and 1 nonvibrating vocal fold, peak collision force correlates more strongly with voice intensity than pitch. Vocal fold collision forces in 1 individual with 2 vibrating vocal folds are of the same order of magnitude as in previous studies. Correlations among peak collision force, voice intensity, and pitch were indeterminate in this participant because of the small number of data points. Sensor modifications are proposed so that it can be used to reliably estimate collision force in individuals with 2 vibrating vocal folds and with changing vocal tract conformations.

Biomechanical Phenomena↗

Endoscopic measurement of vocal fold movement during adduction and abduction.

OBJECTIVES/HYPOTHESIS: Whereas vibration of the vocal folds has been analyzed and modeled in detail, less attention has been paid to quantifying the slower motions of abduction and adduction. Because these gestures reflect neuromuscular function, cartilage geometry, and joint mobility, objective measurement might improve assessment and treatment of patients with neuromuscular or structural disease. STUDY DESIGN: Prospective, observational. METHODS: Twenty-one normal adult volunteers performed a repeated "ee-sniff" task at three rates during flexible endoscopy. Distortion in the images was corrected and frame-by-frame analysis of the angle between the true vocal folds (glottic angle) yielded measures of maximum abduction angle (MAA) and mean angular velocities of abduction (MVAB) and adduction (MVAD). RESULTS: Reliability tests indicated interjudge variability of 3.8 degrees (deg). The mean MAA was 51 deg and ranged from 31 to 77 deg across subjects. The mean MVADs were 229, 309, and 475 deg/s for slow, medium, and fast rates, respectively, and the mean MVABs were 330, 388, and 441 deg/s for slow, medium, and fast rates, respectively. Statistical analysis showed greater influence of gesture rate on adduction than on abduction. CONCLUSIONS: The glottic angle can be reliably measured from flexible endoscopic images and angular velocities of vocal fold abduction and adduction can be determined from analysis of sequential video frames. Accuracy is significantly enhanced by correction of distortion in the images. This approach holds promise for objective characterization of vocal fold function in patients with a variety of disorders.

Adult↗