Polyphenolic Flavonoid Compound Quercetin Effects in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes

Flavonoids are ubiquitous groups of polyphenolic compounds present in most natural products and plants. These substances have been shown to have promising chemopreventive and chemotherapeutic properties with multiple target interactions and multiple pathway regulations against various human cancers. Polyphenolic flavonoid compounds can block the initiation or reverse the promotion stage of multistep carcinogenesis. Quercetin is one of the most abundant flavonoids found in fruits and vegetables and has been shown to have multiple properties capable of reducing cell growth in cancer cells. Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) therapy remains a challenge for hematologists worldwide, and the outcomes for patients with both disorders continue to be poor. This scenario indicates the increasing demand for innovative drugs and rational combinative therapies. Herein, we discuss the multitarget effects of the flavonoid quercetin, a naturally occurring flavonol, on AML and MDS.     

Longitudinal voice changes: Facts and interpretation

To study intraindividual vocal changes over time, a longitudinal research design is preferred. However, this procedure reveals many restrictions concerning methodology and interpretation, especially in cases of (semi)retrospective studies. This is illustrated by an investigation of the voices of 20 male Dutch-speaking reporters of the Belgian Radio Broadcasting service. These men read the same text they did 30 years previously for a digital registration. After having copied the high-quality archival recordings digitally, the results of the acoustical analysis of both recordings (recent and archival) were compared. This was done to search for the contribution of aging. In this article we report on the results of the speaking fundamental frequency (SFF) and the standard deviation of the SFF (SFFsd) as a measure of intraindividual variability, and the voice onset time (VOT). Results indicate that, in connected speech, SFF decreased, SFFsd became more restricted, and the VOT increased strongly. The interpretation of the results compels us to conclude that it is extremely difficult to define the specific effect of aging alone, since it is only one element among many others, including methodological concerns.     

Vocal violence in actors: An investigation into its acoustic consequences and the effects of hygienic laryngeal release training

Acoustic analysis techniques were used to investigate the short-term consequences of vocally violent behavior, and to compare voice production before and after training in hygienic laryngeal release (HLR) techniques. Twenty-seven actors ranging in age from 17 to 48 years were audiorecorded before and after multiple productions of 4 vocally violent behaviors: grunting, groaning, sobbing, and shouting. After training in HLR techniques, the experimental protocol was repeated. Audiorecordings of vowels (produced at 3 pitch levels: modal F0, minimum F0, maximum F0) before and after vocal violence, and before and after HLR training, were analyzed using the Multidimensional Voice Program (4305, Kay Elemetrics Corp, Lincoln Park, NJ). After vocal violence, no consistent acoustic changes were detected for voice generated at modal and minimum F0; however, significant increases in both fundamental frequency range and maximum F0 were observed. After training in HLR techniques, acoustic measures sensitive to pitch and amplitude perturbation, and non-harmonic noise, improved across pitch levels. The results also indicated that vocal training does defend the laryngeal system from undesirable changes related to vocally violent maneuvers that might surface at the extremes of an actor's pitch range. Because the HLR technique used in this investigation was multimodal, interesting questions are raised regarding which aspect of training is primarily responsible for the observed effects. Further study is required to identify such factors.     

The effects of preventive vocal hygiene education on the vocal hygiene habits and perceptual vocal characteristics of training singers

The purpose of the present study was to determine the effects of vocal hygiene education on the vocal hygiene behaviors and perceptual vocal characteristics of untrained singers. Eleven adult untrained singers served as subjects. They attended four 1-hour class sessions on vocal hygiene, including anatomy and physiology of the phonatory mechanism, vocally abusive behaviors, voice disorders commonly seen in singers, and measures to prevent voice disorders. Pre- and postinstruction surveys were used to record subjects' vocal abuses and their perceptions of their speaking and singing voice. They also rated their perceived value of vocal hygiene education. Results revealed minimal changes in vocal hygiene behaviors and perceptual voice characteristics. The subjects did report a high degree of benefit and learning, however.     

Phonomicrosurgical management of vocal fold polyps: The subepithelial microflap resection technique

Vocal fold polyps are typically caused by acute and chronic trauma to the microvasculature of the superficial lamina propria (SLP). Shearing stresses that are induced by hyperfunctional glottal sound production lead to bleeding into the SLP and malformed neo-vascularized masses. Because the primary process does not involve the epithelium, the authors designed a technique to resect hemorrhagic polyps by epithelial cordotomy with partial or complete preservation of the vocal fold epithelium. This approach is different from the traditional microsurgical resection of hemorrhagic polyps by amputation with or without the carbon dioxide laser. Forty patients who underwent microlaryngoscopic resection of hemorrhagic polyps from 1996 through 1998 were reviewed retrospectively. Thirty-six of the 40 procedures were by epithelial cordotomy and subepithelial removal of the polyp contents. Sixteen of 36 were assisted by a subepithelial infusion of saline and epinephrine, and all were 3 mm to 6 mm. Four of 40 polyps were amputated; all of these were less than 3 mm and were pedicled on a narrow base. Cold instruments were used exclusively in all 40 patients. Postoperative laryngeal stroboscopy within 2 weeks revealed improved mucosal wave propagation and improved glottal closure in all 33 patients in whom postoperative strobovideolaryngoscopy was available. The epithelial cordotomy technique was introduced to minimize disturbance of normal SLP and epithelium. Despite the hemorrhagic nature of these lesions, cold instruments could be used exclusively with facility due to careful microdissection between the polyp and the residual normal SLP and the enhanced hemostasis provided by the subepithelial infusion of saline and epinephrine. The rapid return to improved glottal function is the result of this ultra tissue-sparing technique.     

Voice characteristics, effects of voice therapy, and long-term follow-up of contact granuloma patients

This study evaluates the laryngoscopic findings and voice characteristics of male contact granuloma patients before and after voice therapy and at a follow-up about 9 years later. Pre- and posttherapy recordings as well as follow-up recordings were made for 19 granuloma patients. Pretherapy revealed the most salient perceptual voice characteristics were low pitch, monotony, and a high degree of vocal fry and hyperfunction. Interjudge reliability for these traits was high. Immediately following therapy the healed patients (n = 10) had a decrease in hyperfunction, vocal fry, and monotony, while the unhealed patients (n = 9) had an increase in hyperfunction and vocal fry decreased only marginally. Monotony decreased significantly in this group. As regards the acoustic analyses, no significant differences were found in mean fundamental frequency (F₀) or perturbation. At the follow-up assessment 4 patients had granuloma while 15 had normal laryngeal status. Perceptually their voice characteristics resembled those pretherapy independently of the laryngeal findings. The results suggest that reduced hyperfunction and decreased vocal fry may create better circumstances for the healing process at the posterior glottis.     

Dysphonia associated with inhaled steroids

The use of inhaled steroids in the treatment of asthma is not without its complications. In some studies up to 50% of such patients complain of oropharyngeal and voice problems. We present the findings in 22 patients complaining of dysphonia who underwent videostrobolaryngoscopy (VSL) and computerized speech analysis. A number of abnormalities were identified. On VSL, these included mucosal changes (noted in 58%), apposition abnormalities (noted in 43%), and supraglottic hyperfunction (noted in 40%). On speech analysis, cycle-to-cycle irregularity was frequently noted (mean of 39%). Maximum phonation time was reduced in 73%. Our findings did not confirm the widely held views that steroid dysphonia is due primarily to a fungal infection or a steroid-induced adductor myasthenia of the larynx. A larger-scale prospective study is indicated.