Abortion in women with Down syndrome.

BACKGROUND: Nearly two-thirds of pregnancies in women with Down syndrome (DS) end in abortion. The aim of the present study was to determine if these high abortion rates might relate to specific characteristics of women with DS, their life situation and the course of pregnancy. METHODS: In a sample of 351 pregnancies in Switzerland (1998 to 2009), women with DS were compared with women with other forms of intellectual disability (ID) and women without ID, regarding the type of abortion, personal characteristics and pregnancy complications that might increase the probability of abortion. RESULTS: All abortions among women with DS were medically induced. In women with DS and ID, abortions were more likely to occur due to unwanted pregnancy than in women without ID. In addition, women with DS and ID were more often diagnosed with fetal complications and maternal health problems. However, no correlation between fetal complications or maternal health problems and pregnancy outcome was found. CONCLUSIONS: The group differences found do not directly explain the high abortion rates among women with DS. Maternal diagnosis of DS appears to be the most important predictor of abortion. Possible explanations for this finding are discussed.

Distortion product otoacoustic emissions in human hypercholesterolemia.

Epidemiological and experimental studies suggest that hypercholesterolemia promotes the development of sensorineural hearing loss; however, the underlying cellular pathomechanism remains obscure. In the present study, 20 healthy subjects and 20 patients with familial hypercholesterolemia were compared with respect to their hearing function. None of the 40 persons reported any history of hearing disorder. In accordance with this subjective impression, mean hearing thresholds were within the normal, age-dependent ranges in both groups. In contrast, the single-generator distortion product otoacoustic emissions (sgDPOAE) were reduced at and above 4 kHz. Input-output functions of DPOAE could be subdivided into three groups: (i) normal, with unity slope at low intensities and slope less than unity (0.24+/-0.07 dB/dB at higher intensities; (ii) pathologic, described by a single straight line; (iii) ill-defined, with data usually indistinguishable from the background noise level. The ill-defined DPOAE behavior was only found in patients with hypercholesterolemia; namely, for 25% of patients at f(2)=1.5 kHz and for 50% at f(2)=4 kHz. Patients belonging to the pathologic and ill-defined DPOAE groups had significantly (P<0.05) higher total serum cholesterol and LDL-cholesterol levels compared with subjects from the normal DPOAE group. While hearing thresholds of patients with ill-defined growth functions were not statistically different from those of normal subjects, speech scores were significantly reduced in these cases. The data imply that nonlinear mechanical processes in the cochlea are compromised in hypercholesterolemic patients.

Clinical experience with injectable collagen for vocal fold augmentation.

Injectable collagen appears to be safe and effective in treating glottic insufficiency. Fifty-four patients received vocal-fold injections of Zyderm Collagen Implant and their responses were followed for as long as 2 years. Videostroboscopy affords the best assessment of glottic function and correlates well with vocal quality. Maximum phonation time and transglottic airflow are the most sensitive measures of glottic efficiency; follow-up studies indicate that responses to treatment vary at 1 week, tend to stabilize by 3 months, and show only slight decrement over 1 year. One patient experienced a delayed hypersensitivity reaction, but it did not adversely affect his result. The use of cross-linked preparations of collagen should decrease the incidence of such responses. Treated patients were divided into diagnostic groups. Patients with bilaterally scarred vocal folds did not appear to respond optimally to collagen injection. Vocal rehabilitation was better if patients had at least one normal vocal fold. The best results occurred in patients with unilateral vocal fold paralysis and pre-existent bowing or atrophy did not affect these results. Collagen should be injected in the plane of the vocal ligament for best results; if the injection is too deep the implant is resorbed, and if too superficial, vocal-fold vibration is impaired.

Sulcus vocalis in laryngeal cancer: a histopathologic study.

The incidental finding of sulcus vocalis in surgical specimens of patients with laryngeal cancer prompted this review. Sulcus deformities were histologically identified in 28 (48%) of 58 whole-mount coronal serial-sectioned laryngeal specimens procured from laryngeal cancer patients. The lesions were analyzed, described, and graded. A control group of 20 larynges, obtained from autopsies of patients without known laryngeal pathology, were similarly processed, and whole-mount histologic sections were studied. Four of these specimens (20%) also demonstrated sulcus deformities. In the control group, the shape and location of the sulci were similar, but the lesions were smaller than in the cancer group. The sulcus lesions revealed chronic inflammation of the subepithelial tissues with vascular ingrowth and fibrosis of the superficial lamina propria (Reinke's space); in the cancer group the sulcus was usually on the opposite vocal fold, where irritation from the tumor might be anticipated. Although the etiology of the sulci remains controversial, these findings suggest that irritation and inflammation might play a role in the pathogenesis of sulcus vocalis.

Anterior commissure microwebs associated with vocal nodules: detection, prevalence, and significance.

Vocal fold nodules are a common cause of dysphonia generally attributed to vocal abuse. Anterior commissure microwebs have been reported as an incidental finding in surgical patients with nodules. In a series of 105 nodule patients evaluated at the University of Wisconsin Clinical Science Center voice laboratory (1987-1992), 11 microwebs were identified. Ten of these microweb patients were among the 20 nodule patients who did not respond to voice therapy and underwent microsurgery. In patients with nodules whose hoarseness is refractory to voice therapy, symptoms that occur early in life suggest the presence of occult vocal fold pathology. Microweb detection requires a high index of suspicion, observation during maximal vocal fold abduction, and clearance of secretions from the anterior commissure. Definitive identification is facilitated by gentle separation of the anterior vocal folds during direct microlaryngoscopy. The presence of these tiny shelves of tissue might be coincidental, or they might represent another expression of the tissue response to traumatic factors known to produce vocal nodules. We found little difference in vocal function parameters between two similar groups of nodule patients, one with and one without associated microwebs. Further work is needed to determine the significance of microwebs.

Autologous collagen vocal fold injection: a preliminary clinical study.

This preliminary study reports the first use of injectable autologous collagen for vocal fold augmentation. In previous studies, the authors showed cross-linked bovine collagen to be effective in more than 150 patients with glottic incompetence, particularly those with focal defects or scarred or atrophic vocal folds. However, concerns about possible adverse immunologic responses to the bovine material have limited its use. The authors studied eight patients with difficult vocal fold pathology, including sulcus vocalis, atrophy, and scarring secondary to trauma and cordectomy. Skin was harvested under local anesthesia, processed into a naturally cross-linked injectable form (Autologen), and injected using indirect laryngoscopy. Voice production was evaluated prior to the injection and at intervals after the injection, using subjective, perceptual, aerodynamic, acoustic, and videostroboscopic assessments. The results indicate that autologous collagen is comparable to injectable bovine collagen in the management of several difficult glottic insufficiency problems and that the likelihood of a hypersensitivity response is negligible. Unlike bovine collagen preparations, Autologen does not require breakdown of the natural collagen molecule, so it is anticipated that this material will be better tolerated and more stable over time.

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.

Magnetic resonance imaging (MRI) assessment of vocal fold medialization surgery.

Historically, clinicians have used subjective assessment and perceptual judgments, supplemented with acoustic measures, aerodynamic studies, and videostroboscopy, to determine the effects of phonosurgery. When phonosurgical results are poor, magnetic resonance imaging (MRI) can be useful in determining how the surgical modifications contributed to the anatomical and functional status of the vocal folds. The authors present examples of MRI following vocal fold medialization by injection, thyroplasty, and arytenoid adduction. Findings reveal that the superior contrast resolution of MRI can precisely identify placement and persistence of injected implants and is particularly helpful in showing effects of the size and shape of alloplastic prostheses on vocal fold displacement. Such information is useful in troubleshooting suboptimal results and in planning revision thyroplasty by defining modification in the design of prostheses and the placement of cartilaginous windows in medialization thyroplasty. MRI can also aid in confirming indications for and limitations of certain procedures.

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.

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.

A preliminary study of injectable collagen in human vocal fold augmentation.

Soluble bovine collagen was injected for vocal fold augmentation in 27 patients with glottic insufficiency. Preliminary observations show that glottic closure was enhanced in all patients with no serious complications. Subjective and objective measures of vocal efficiency indicated improvement with reduction in airflow, improved glottic closure, and increased vocal intensity. Recent studies that reveal distant migration of injected Teflon suggest the need for the development of a safe biologic material for soft tissue augmentation. Collagen appears to satisfy criteria as an ideal bioimplant, tends to soften scar tissue, and is structurally similar to natural collagen in the human vocal fold. Further longitudinal studies and the development of potentially more stable cross-linked collagen preparations seem indicated.

Teflon vocal fold augmentation: failures and management in 28 cases.

Although vocal fold augmentation by Teflon injection has been the mainstay of treatment for glottic insufficiency for three decades, the success and safety of this treatment have been overstated. Twenty-eight patients who manifested poor or complicated Teflon results between 1984 and 1991 were evaluated using acoustic, aerodynamic, videostroboscopic, perceptual, and subjective patient self-evaluation of voice, both before and after our management of these complications. Most of these had Teflon granulomas; subglottic overfilling was the most common condition. In most instances such management included microsurgical removal of the Teflon granuloma. Voice measures that were abnormal before correction tended to improve and move into the normal range, although the resultant voices were not totally normal. Degree of improvement varied depending on the Teflon-induced tissue changes and the methods of correction subsequently used. The worst results were in patients with scarring, atrophy, and bilaterally mobile vocal folds, for whom Teflon should never have been injected. Teflon injection should be reserved for those instances in which it is clearly indicated and the surgeon is skilled in the technique of intrafold injection.

An objective assessment of voice production after radiation therapy for stage I squamous cell carcinoma of the glottis.

Radiation therapy has been the primary treatment for early glottic carcinoma, especially when restoration of normal voice is essential; yet objective evidence of the status of vocal function after treatment is lacking. The purpose of this study was to assess vocal characteristics of patients with glottic carcinoma after they had undergone radiation therapy. Twenty males, who had previously been treated with external beam irradiation for T1N0M0 squamous cell carcinoma with no subsequent evidence of recurrence, volunteered for this study. Laryngovideostroboscopic, acoustic, aerodynamic, and perceptual measures of vocal function were used to determine the characteristics of voice production. Acoustic indices were compared to those of a normal group of 30 age-matched volunteers, and the other measures were compared to established values reported in the literature. On acoustic analysis, the study group was characterized by significantly worse voice production than their counterparts. A high degree of intersubject variability was noted that could not be accounted for in terms of variables in treatment and medical history. The aerodynamic, spectral, and video-stroboscopic findings correlated well; this indicated a poor vibratory source, characterized by diffuse stiffness. Further work is necessary in order to compare vocal function after endoscopic laser and conventional conservative excision.

Indirect laryngoscopic approach for injection of botulinum toxin in spasmodic dysphonia.

Spasmodic dysphonia is a focal dystonia that causes a loss of the fine control of intrinsic laryngeal muscles and produces a strained staccato voice. Temporary relief from symptoms has been reported in patients treated with botulinum toxin percutaneously injected into the thyroarytenoid muscle. A newly developed method of treatment differs from reported methods by increasing the accuracy of botulinum toxin placement, reducing soft tissue trauma, and applying basic scientific information about the functional histology of intrinsic laryngeal musculature. Sixteen patients with primarily adductor spasmodic dysphonia were treated. Initial assessment included laryngeal examination by indirect laryngoscopy, videoendoscopy, and stroboscopy, neurology examination (including laryngeal EMG), and vocal function studies with acoustic analysis and aerodynamic studies. A device originally designed for collagen injection allowed the precise microdelivery of toxin to the thyroarytenoid muscle. Indirect laryngoscopy was used to direct the needle, in an attempt to cover a broad area of motor end plates. The minimally effective dose was titrated for each patient, to avoid paralysis and preserve laryngeal function. All patients showed improved voices after treatment. There were no major complications. The basic technique can be performed in the otolaryngologist's office and does not require electromyography equipment or expertise.

Muscle tension dysphonia and spasmodic dysphonia: the role of manual laryngeal tension reduction in diagnosis and management.

Excessive activity of the extralaryngeal muscles affects laryngeal function and contributes to a spectrum of interrelated symptoms and syndromes including muscle tension dysphonia and spasmodic dysphonia. Recognition of the role of extralaryngeal tension is helpful in ensuring proper diagnosis and selection of appropriate treatment. This report demonstrates the application of manual laryngeal musculoskeletal tension reduction techniques in the diagnosis and management of laryngeal hyperfunction syndromes. The manual technique consists of focal palpation to determine 1) extent of laryngeal elevation, 2) focal tenderness, 3) voice effect of applying downward pressure over the superior border of the thyroid lamina, and 4) extent of sustained voice improvement following circum-laryngeal massage. The clinical utility of this innovative approach is discussed.

Role of injectable collagen in the treatment of glottic insufficiency: a study of 119 patients.

Injectable bovine collagen has been used for treatment of glottic insufficiency at the University of Wisconsin Clinical Science Center since 1983. This report reviews our experience in treating 119 patients with a variety of vocal fold disorders manifested by glottic insufficiency. Many of the patients were referred because of prior treatment failures or problems that were impossible to treat with other modalities. Results were assessed by comprehensive voice evaluations using subjective patient self-assessments, perceptual judgments made by a panel of experts who had no prior knowledge of the study, objective assessments, and videostroboscopy. Objective assessment included vocal function measures and acoustic analysis. Results indicate that collagen not only is comparable to other injection filler substances but also has unique advantages as a bioimplant. Collagen injection seems uniquely suited for treatment of several problems, including vocal fold atrophy, focal defects, minimal glottic insufficiency, and scarred vocal folds that are not managed optimally with Teflon injection. Overall there were no serious complications and treatment was effective for a broad spectrum of problems. In most instances the correction persisted, and in those instances in which injected collagen seemed improperly distributed, the vocal fold was recontoured or the implant removed without appreciable damage to the surrounding tissues. Injectable collagen has been extensively studied and deserves to be included in the armamentarium of the laryngeal surgeon.

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.

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.

Measurement of vocal function.

Objective measurement of vocal function, e.g., acoustical analysis, is emerging as a necessity in clinical practice. Voice data assist in determining the diagnosis and prognosis of many voice disorder patients and provide documentation of the vocal quality before, during, and after treatment.

Personality traits and psychological factors in voice pathology: a foundation for future research.

It has been argued that personality, emotions, and psychological problems contribute to or are primary causes of voice disorders and that voice disorders in turn create psychological problems and personality effects. This article (a) briefly reviews the literature surrounding the role of psychological and personality processes in individuals with functional dysphonia (FD), vocal nodules (VN), and spasmodic dysphonia (SD); (b) provides an overview of recent concepts in personality and trait structure; and (c) summarizes the fundamental tenets of a theoretical synthesis proposed by Roy and Bless (2000) to explain the dispositional bases of FD and VN. This theory links FD and VN to the signal sensitivities and behavioral response biases of neurotic introverts and neurotic extraverts, respectively. In a companion article, the merits of the Roy and Bless theory are evaluated.