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Biomedical subjects

Linda Lee

Publications and source records attributed to Linda Lee.

At least 19 recordsLinked to original sources
PubMed2006

Pediatric Voice Handicap Index (pVHI): a new tool for evaluating pediatric dysphonia.

PURPOSE: The Voice Handicap Index (VHI) is widely used and accepted into adult clinical practice. The present study was initiated to adapt the VHI to the pediatric population and to validate it in the form of a parental proxy. METHODS: The initial modification of the adult VHI involved changing the language of the statements to reflect a parent's responses about their child and eliminating questions that would not relate to children. It was administered in conjunction with 10 open-ended questions regarding the impact of the child's voice quality on overall communication, development, education, social and family life. The pVHI was then modified in content and language, and the final 23-item parental proxy product was used for the validation process. The modified pVHI was administered to two groups of patients following IRB approval from Cincinnati Children's Hospital Medical Center. RESULTS: Normative data was obtained from 45 parents of healthy children. The group consisted of 21 males, age ranges 3-12 years old. The mean scores of the total pVHI and its subscales are: functional (F) 1.47, physical (P) 0.20, emotional (E) 0.18 and total (T) 1.84. The test group consisted of 33 guardians of children presenting for a voice evaluation pre- or post-laryngotracheal reconstruction. This group differed greatly from the control group on each subscale and total score. The mean scores of the airway group were as follows: F 13.94, P 15.48, E 12.15 and T 41.58. Test-retest reliability of the total pVHI score was measured using Pearson's correlation coefficient. The scores were 0.95, 0.77, 0.79 and 0.82, respectively. A correlation matrix for pVHI subscore and total score showed significance, with results similar to those reported for the original adult VHI. CONCLUSIONS: The aim of the present study was to modify the VHI to serve a similar role in the evaluation of the effects of dysphonia on the pediatric population. The statistical results reveal a high correlation between the VHI and the pVHI. The pVHI provides a high internal consistency and test-retest reliability. This tool will be utilized to follow a child's development following surgical, medical and behavioral interventions.

Adolescent↗
PubMed2006

Voice problems of future speech-language pathologists.

Students training to be educators frequently exhibit voice disorders prior to employment. To date, there exist no similar studies of future speech-language pathologists (SLPs). The study is designed as a prospective, nonrandomized survey. The objective of this study is to determine the voice problems of first year graduate students training to be SLPs. Participants were 104 first year graduate students majoring in speech-language pathology at two universities. The Quick Screen for Voice was administered. Participants who failed completed a questionnaire regarding voice problems, medical history, daily habits, and voice use. When responses further indicated voice-related problems, endoscopic examination was completed. Fourteen percent (N=15) of the participants failed the screening by demonstrating two or more abnormal voice characteristics. These included persistent glottal fry (present in all who failed), low habitual pitch, juvenile resonance, hoarse, breathy, or strained phonation, abnormally low pitch on sustained vowels, and voice breaks during the frequency range. Twelve percent (N=12) failed both the screening and follow-up questionnaire. Responses included self-reported dysphonia, medical history with voice-related side effects, difficulty with excessive voice use, and voice problems occurring daily or weekly. Endoscopic evaluation showed one participant with bilateral vocal nodules. The results suggest that voice problems among future SLPs (12%) are more common than the 3-9% reported in the general population and similar to the 11% previously reported for teachers. However, future SLP voice problems are less frequent than those reported among education majors (21%) and all college students (17%). Faculty should identify students with voice problems and emphasize optimal voice use in classroom and clinical settings.

Adult↗
PubMed2006

Reliability of speech-language pathologist and otolaryngologist ratings of laryngeal signs of reflux in an asymptomatic population using the reflux finding score.

OBJECTIVE: To determine inter- and intrajudge agreement in rating signs of laryngopharyngeal reflux (LPR) under "ideal" conditions: Experienced coworkers in a practice devoted to voice-disordered patients, raters trained in the items on a standardized scale, raters from both speech-language pathology (SLP) and otolaryngology, and raters of asymptomatic participants. STUDY DESIGN: Prospective study using a scale to rate videolaryngoscopic examinations. METHODS: Two SLPs and two otolaryngologists used the Reflux Finding Scale (RFS) to independently rate videotapes of endoscopic examinations for 30 participants asymptomatic of reflux. RESULTS: Thirteen (43%) were assigned a total score >7, indicative of LPR, by at least one rater. Intraclass correlation coefficients showed a significant lack of agreement in total scores provided by the otolaryngologists and by all raters combined. One otolaryngologist and the two SLPs demonstrated good interrater agreement in total scores. McNamar's statistic and Poisson regression modeling showed differences in rater agreement for many individual items. Repeated ratings of four participants showed no significant differences, indicating good intrarater reliability. CONCLUSIONS: Level of rater agreement regarding the presence and the severity of physical findings attributed to LPR within and between otolaryngologists and SLPs differed. Given the role each profession plays in the diagnosis and treatment of LPR and related voice disturbances, higher levels of interprofessional agreement are desired. Results support the need for greater consensus among professionals regarding the discreet features of physical findings associated with LPR, a fuller understanding of normal variants, and greater emphasis on interrater reliability when rating physical findings.

Adult↗
PubMed2006

Selective role of PKCbeta enzymatic function in regulating cell survival mediated by B cell antigen receptor cross-linking.

Cross-linking of the B cell antigen receptor (BCR) results in the activation of several protein tyrosine kinases leading to phospholipase C-gamma2-dependent phospholipid hydrolysis and Ca2+ mobilization, followed by activation of the protein kinase C (PKC) family members. Sustained Ca2+ release in B lymphocytes is dependent on the membrane localization and activation of the protein tyrosine kinase BTK. Ca2+ release is a tightly regulated process involving BTK membrane localization through its phosphorylation by PKCbeta. A selective role of PKCbeta in B cell signaling was first revealed by the characterization of PKCbeta knockout mice, which displayed decreased B cell proliferation in response to various mitogenic stimuli. However, it is not clear whether the B cell defects displayed by the PKCbeta knockout mice are due a B cell developmental defect or the scaffolding function of PKCbeta, resulting in a defect in the recruitment or formation of signal transducing complex molecules. Thus, in this report we investigated the effects of pharmacologic inhibition of the catalytic function of PKCbeta on B cell survival and growth. Treatment of Daudi B lymphoma cell line with a selective PKCbeta inhibitor, LY333531, inhibited anti-IgM-induced phosphorylation of BTK on Ser180 in a concentration-dependent manner, which was concomitant with an increase in BTK activation, and Ca2+ mobilization. In primary splenic B cells, LY333531 inhibited BCR-induced B cell proliferation, but did not affect basal or LPS-induced proliferation. Finally, LY333531 treatment resulted in the induction of apoptosis of anti-IgM-activated B cells, which corroborated with their inability to up-regulate pro-survival factors, Bcl-X(L) and Bcl-2. These results support the important and selective role of the PKCbeta enzymatic function in controlling Ca2+ release during BCR signaling leading to B lymphocyte survival and growth.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2006

Pediatric laryngotracheal stenosis and airway reconstruction: a review of voice outcomes, assessment, and treatment issues.

Laryngotracheal stenosis is defined as a congenital or acquired narrowing of the airway. Congenital causes may include subglottic membranous or cartilaginous narrowing. Acquired causes may include trauma due to prolonged endotracheal or tracheal intubation or laryngotracheal injury. Although advances have been made over the past 30 years in reconstructive surgeries to improve airway patency in these patients, long-term laryngeal function for voice production is not well defined in this population. This review examines causes, symptoms and signs, and methods for diagnosing laryngotracheal stenosis. Surgical management procedures are briefly summarized. The current literature on voice outcomes is summarized. The predominant voice characteristics in the population are presented, although results are challenged by the heterogeneity of voice presentation and paucity of data from instrumental measures. Considerations for subjective and instrumental assessment, measures of quality of life, instrumental methods, and treatment options specific to the needs of this population are discussed. Research strategies to identify long-term outcomes of surgical and behavioral treatments in this population are posed.

Child↗
PubMed2006

Effects of prolonged loud reading on normal adolescent male voices.

PURPOSE: The purpose of this article was to test the effects of vocal loading in healthy, peripubescent teenage boys. It was hypothesized that select acoustic measures, ratings of physical appearance of the larynx, and self-ratings of physical effort and vocal quality in the experimental group would significantly change in response to 2 hr of prolonged loud reading. METHOD: In this prospective, repeated measures study, 25 boys aged 13-16 years were randomly assigned to either an experimental group (2 hr of continuous loud reading) or a control group (silent reading with brief periods of conversation). Pre-post acoustic, videoendoscopic, and perceptual data including self-ratings were collected. Postreading recovery changes were tracked by monitoring average reading fundamental frequency (F0) and intensity for 20 min following cessation of the reading task. RESULTS: The experimental group demonstrated statistically significant differences before and after prolonged loud reading for three variables: F0 (p < .01), self-ratings of vocal quality (p < .01), and physical effort (p < .01). No pre-post changes were evident in the control group. In the experimental group, posttest return of F0 to pretest levels occurred within 20 min. Self-ratings revealed that the boys felt that their voice quality worsened and physical effort increased during the experimental task. Expert ratings did not detect any significant differences in either the perceptual quality of the experimental group's voices or their videoendoscopic images. IMPLICATIONS: These findings demonstrate that prolonged loud reading can induce temporary but measurable changes in F0 and in self-perception of vocal function in adolescent males who are experiencing a period of rapid laryngeal growth. The underlying mechanism for these changes remains unclear and warrants continued investigation. Furthermore, the results suggest that in the pubescent male population, comparable vocal loading tasks encountered in daily use should not result in long-term negative effects.

Acoustics↗
PubMed2005

Analysis of green fluorescent protein expression in transgenic rats for tracking transplanted neural stem/progenitor cells.

Green fluorescent protein (GFP) expression was evaluated in tissues of different transgenic rodents--Sprague-Dawley (SD) rat strain [SD-Tg(GFP)Bal], W rat strain [Wistar-TgN(CAG-GFP)184ys], and M mouse strain [Tg(GFPU)5Nagy/J]--by direct fluorescence of native GFP expression and by immunohistochemistry. The constitutively expressing GFP transgenic strains showed tissue-specific differences in GFP expression, and GFP immunohistochemistry amplified the fluorescent signal. The fluorescence of stem/progenitor cells cultured as neurospheres from the ependymal region of the adult spinal cord from the GFP SD and W rat strains was assessed in vitro. After transplantation of the cells into wild-type spinal cord, the ability to track the grafted cells was evaluated in vivo. Cultured stem/progenitor cells from the SD strain required GFP immunostaining to be visualized. Likewise, after transplantation of SD cells into the spinal cord, immunohistochemical amplification of the GFP signal was required for detection. In contrast, GFP expression of stem/progenitor cells generated from the W strain was readily detected by direct fluorescence both in vitro and in vivo without the need for immunohistochemical amplification. The cultured stem/progenitor cells transplanted into the spinal cord survived for at least 49 days after transplantation, and continued to express GFP, demonstrating stable expression of the GFP transgene in vivo.

Animals↗
PubMed2005

A case of Bowen's disease and small-cell lung carcinoma: long-term consequences of chronic arsenic exposure in Chinese traditional medicine.

Chronic arsenic toxicity occurs primarily through inadvertent ingestion of contaminated water and food or occupational exposure, but it can also occur through medicinal ingestion. This case features a 53-year-old lifetime nonsmoker with chronic asthma treated for 10 years in childhood with Chinese traditional medicine containing arsenic. The patient was diagnosed with Bowen's disease and developed extensive-stage small-cell carcinoma of the lung 10 years and 47 years, respectively, after the onset of arsenic exposure. Although it has a long history as a medicinal agent, arsenic is a carcinogen associated with many malignancies including those of skin and lung. It is more commonly associated with non-small-cell lung cancer, but the temporal association with Bowen's disease in the absence of other chemical or occupational exposure strongly points to a causal role for arsenic in this case of small-cell lung cancer. Individuals with documented arsenic-induced Bowen's disease should be considered for more aggressive screening for long-term complications, especially the development of subsequent malignancies.

Administration, Oral↗
PubMed2005

Using the modified Schirmer test to measure mouth dryness: a preliminary study.

BACKGROUND: Current methods of measuring saliva volume often are difficult to perform in a general dental or medical office setting. This study seeks to determine whether the Schirmer test for measuring eye dryness can be modified to measure mouth dryness. METHODS: The authors performed a modified Schirmer test (MST) on a control group composed of 41 healthy adult volunteers and a study group composed of 10 patients who had received head and neck radiation and 10 patients who had oral chronic graft-versus-host disease (CGVHD). The authors placed the strip on the floor of each subject's mouth and took readings at one minute, two minutes and three minutes. Fourteen control subjects also spat into a container over a five-minute interval, and the authors weighed the collected saliva. RESULTS: The mean reading for the control subjects at three minutes was 29.5 millimeters, while the mean reading for the test subjects was 6.9 mm (P < .00005). CONCLUSIONS: The results of the MST were able to distinguish between healthy adult volunteers and subjects who experienced profound xerostomia and hyposalivation. CLINICAL IMPLICATIONS: The MST as used in this preliminary study is an objective, inexpensive, easy-to-perform and well-tolerated test for measuring mouth dryness. It readily distinguishes between patients who are healthy and asymptomatic and those who experienced profound xerostomia and hyposalivation.

Adult↗
PubMed2004

Quick screen for voice and supplementary documents for identifying pediatric voice disorders.

Three documents are provided to help the speech-language pathologist (SLP) identify children with voice disorders and educate family members. The first is a quickly administered screening test that covers multiple aspects of voice, respiration, and resonance. It was tested on 3000 children in kindergarten and first and fifth grades, and on 47 preschoolers. The second document is a checklist of functional indicators of voice disorders that could be given to parents, teachers, or other caregivers to increase their attention to potential causes of voice problems and to provide the SLP with information pertinent to identification. The final document is a brochure with basic information about voice disorders and the need for medical examination. It may be used to help the SLP educate parents, particularly about the need for laryngeal examination for children who have been identified as having a voice problem.

Adolescent↗
PubMed2003

Oral bioavailability of pentachlorophenol from soils of varying characteristics using a rat model.

Evidence accumulated during the last two decades suggests that only a fraction of any chemical in soil is available to organisms, and soil-related effects on bioavailability should be considered in optimizing soil remediation cleanup levels. In the current study, the absolute and relative bioavailabilities of pentachlorophenol (PCP) from freshly spiked and environmentally aged soils varying in organic carbon content, clay content, and pH were examined using a rat model. PCP is a broad-spectrum biocide widely used as a wood preservative, and thus is ubiquitous in the environment. Soils and corn oil containing equivalent levels of PCP were administered to male Sprague-Dawley rats by gavage at 2 dose levels: 100 and 200 microg/kg body weight. Equivalent doses were also given intravenously. The areas under the plasma concentration of PCP versus time curves were calculated, and absolute and relative bioavailabilities of PCP from each soil were determined. At a dose of 100 microg/kg body weight, the absolute bioavailabilities of PCP across soils ranged from 36% to 65%, and the relative bioavailabilities ranged from 48% to 82%. At the higher dose level (200 microg/kg body weight), absolute and relative bioavailability ranges were somewhat higher at 46% to 77% and 52% to 87%, respectively. All soils decreased absolute PCP bioavailability significantly at both dose levels and relative bioavailability at the lower PCP dose level. At the higher dose level, only one of the two field-contaminated soils decreased the relative PCP bioavailability. The data indicate that PCP-soil interactions do significantly decrease the oral bioavailability of PCP from soil, but no obvious correlation was observed between soil properties and bioavailabilities.

Administration, Oral↗
PubMed2003

Identification of Cre residues involved in synapsis, isomerization, and catalysis.

The Cre protein of bacteriophage P1 is a tyrosine recombinase and catalyzes recombination via formation of a covalent protein-DNA complex and a Holliday junction intermediate. Several co-crystal structures of Cre bound to its target lox site have provided novel insights into its biochemical activities. We have used these structures to guide the mutagenesis of several Cre residues that contact the lox spacer region and/or are involved in intersubunit protein-protein interactions. None of the mutant proteins had significant defects in DNA binding, DNA bending, or strand-specific initiation of recombination. We have identified novel functions of several amino acids that are involved in three aspects of the Cre reaction. 1) Single mutation of several NH2-terminal basic residues that contact the spacer region of loxP caused the accumulation of Holliday junction (HJ) intermediates but only a modest impairment of recombination. These residues may be involved in the isomerization of the Holliday intermediate. 2) We identified three new residues (Arg-118, Lys-122, and Glu-129) that are involved in synapsis. Cre R118A, K122A, and E129Q were catalytically competent. 3) Mutations E129R, Q133H, and K201A inactivated catalysis by the protein. The function of these Cre residues in recombination is discussed.

Bacteriophage P1↗
PubMed2003

Cre induces an asymmetric DNA bend in its target loxP site.

Cre initiates recombination by preferentially exchanging the bottom strands of the loxP site to form a Holliday intermediate, which is then resolved on the top strands. We previously found that the scissile AT and GC base pairs immediately 5' to the scissile phosphodiester bonds are critical in determining this order of strand exchange. We report here that the scissile base pairs also influence the Cre-induced DNA bends, the position of which correlates with the initial site of strand exchange. The binding of one Cre molecule to a loxP site induces a approximately 35 degrees asymmetric bend adjacent to the scissile GC base pair. The binding of two Cre molecules to a loxP site induces a approximately 55 degrees asymmetric bend near the center of the spacer region with a slight bias toward the scissile A. Lys-86, which contacts the scissile nucleotides, is important for establishing the bend near the scissile GC base pair when one Cre molecule is bound but has little role in positioning the bend when two Cre molecules are bound to a loxP site. We present a model relating the position of the Cre-induced bends to the order of strand exchange in the Cre-catalyzed recombination reaction.

Amino Acid Substitution↗
PubMed2003

Sequence of the loxP site determines the order of strand exchange by the Cre recombinase.

Conservative site-specific recombinases of the integrase family carry out recombination via a Holliday intermediate. The Cre recombinase, a member of the integrase family, was previously shown to initiate recombination by cleaving and exchanging preferentially on the bottom strand of its loxP target sequence. We have confirmed this strand bias for an intermolecular recombination reaction that used wild-type loxP sites and Cre protein. We have examined the sequence determinants for this strand preference by selectively mutating the two asymmetric scissile base-pairs in the lox site (those immediately adjacent to the sites of cleavage by Cre). We found that the initial strand exchange occurs preferentially next to the scissile G residue. Resolution of the Holliday intermediate thus formed takes place preferentially next to the scissile A residue. Lys86, which contacts the scissile nucleotides in the Cre-lox crystal structures, was important for establishing the strand preference in the resolution of the loxP-Holliday intermediate, but not for the initiation of recombination between loxP sites.

Base Pairing↗
PubMed2003

Laryngeal function and vocal fatigue after prolonged reading in individuals with unilateral vocal fold paralysis.

The purpose of the present study was to examine the effect of prolonged loud reading, intended to induce fatigue, on vocal function in adults with unilateral vocal fold paralysis (UVFP). Subjects were 20 adults, 37-60 years old, with UVFP secondary to recurrent laryngeal nerve paralysis. Subjective ratings and instrumental measures of vocal function were obtained before and after reading. Statistical analysis revealed subjects rated their vocal quality and physical effort for voicing more severely following prolonged loud reading, whereas expert raters did not detect a significant perceptual difference in vocal quality. Reading fundamental frequency (F0) was significantly increased following prolonged loud reading, as were mean airflow rates at all pitch conditions. Maximum phonation times for comfort and low pitches significantly decreased during posttests. Multiple regression analyses revealed significant associations between ratings of posttest physical effort and select posttest measures. Interpretation of results indicates the prolonged loud reading task was successful in vocally fatiguing most of the UVFP subjects. Key physiologic correlates of vocal fatigue, in individuals with UVFP, include further reduction of glottic efficiency, resulting in decreased regulation of glottic airflow and a temporary destabilization of speaking fundamental frequency.

Adult↗