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PubMed1992

Synthesis and anticonvulsant activity of enaminones.

A new series of novel enaminones has been synthesized from cyclic beta-dicarbonyl precursors which were condensed with morpholine, pyrrolidine, phenethylamine, hydrazines, substituted benzyl amines, and substituted anilines. These compounds were subsequently evaluated for anticonvulsant activity in a variety of anticonvulsant models by the National Institute of Neurological and Communicative Disorders and Stroke and in our laboratory. Several of these compounds exhibited potent anticonvulsant activity with a remarkable lack of neurotoxicity. The most active analog, methyl 4-[(p-chlorophenyl)amino]-6-methyl-2-oxo-cyclohex-3-en-1-oate++ + (27), was protective in the maximal electroshock (MES) seizure test in the rat with an oral ED50 of 5.8 mg/kg with no toxicity noted at doses up to 380 mg/kg, thus providing a protective index (TD50/ED50) of greater than 65.5. A similar protective index for 27 was noted upon intraperitoneal (ip) administration in mice. The anticonvulsant effect of 27 occurred within 15 min of administration and the compound remained active beyond 4 h. Compound 27 was also active in the rat corneal kindled model. The application of Free-Wilson analysis to structure-activity correlation in this series is discussed.

Amines↗

PubMed1991

Synthesis and anticonvulsant activity of imidooxy derivatives.

Previous results of anticonvulsant activity in several imidooxy carboxylates related to (aminooxy)acetic acid in young chicks, prompted an in-depth reinvestigation of these analogues in mice. A series of 22 succinimidooxy, phthalimidooxy, and naphthalimidooxy carboxylates were synthesized and evaluated for anticonvulsant activity by the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS). Methyl (succinimidooxy)acetate (2d), ethyl (succinimidooxy)acetate (2e), methyl (phthalimidooxy)acetate (3d), ethyl (phthalimidooxy)acetate (3e), and ethyl 2-(phthalimidooxy)propionate (3g), which were initially found to be active as anticonvulsants in young chicks were uniformly inactive in the Phase I seizure tests involving maximal electroshock (MES), pentylenetetrazol (scMet), or neurologic toxicity toxicity (Tox). Several newer analogues, ethyl (succinimidooxy)formate (2c) and methyl 3-(phthalimidooxy)-2-methylacrylate (4h) were found to be active in the scMet (3a) or both (4h) evaluations. Most interesting was the anticonvulsant results of N-(benzyloxy)-2-azaspiro[4,4] nonane-1,3-dione (5b), which displayed anti-MES activity and a protective index (TD50/ED50) of greater than 4.5.

Animals↗

PubMed1986

Cycloheximide analogues as potential anticonvulsants.

A series of 22 cycloheximide analogues in which the substituents on the cycloheximide ring and imide nitrogen were varied, the glutarimide ring was changed to a succinimide ring, and the ring and/or side-chain oxygens were present as ketone and/or alcohol groups were prepared and sent to the Anticonvulsant Drug Development program of the National Institute of Neurological and Communicative Disorders and Strokes for evaluation as anticonvulsants. Three compounds, namely cycloheximide (1a), 2-methyl dione 2c, and dihydrocycloheximide (4a), were further evaluated in Phase II testing for quantification of maximum activity with the latter eventually progressing to Phase IV and Phase VI screens.

Animals↗

PubMed1979

Synthesis of imidazolidinediones and oxazolidinediones from cyclization of propargylureas and propargyl carbamates.

A synthetic procedure for the preparation of imidazolidinediones by the base-catalyzed cyclization of propargylureas is described. This method appears to be the most versatile way of obtaining these compounds containing tertiary groups substituted on ring-nitrogen number 3. One of these derivatives, 3-tert-butyl-5,5-dimethyl-2,4-imidazolidinedione (1a), has shown a moderate level of subcutaneous metrazole seizure threshold activity (scMet indicates potential for control of petit mal epileptic seizures) in control screens on mice, as determined by the National Institute of Neurological and Communicative Disorders and Stroke.

Animals↗

PubMed1994

Synthesis and evaluation of amino analogues of valproic acid.

Valproic acid, an antiepileptic drug, is extensively metabolized in humans. Two putative metabolites, 2-n-propyl-3-aminopentanoic acid (3-aminovalproic acid, 3-amino-VPA; 2a) and 2-n-propyl-4-aminopentanoic acid (4-amino-valproic acid, 4-amino-VPA; 4a), which may result from the transamination of the respective keto acids 1a and 3a may explain the unusual extended seizure protection elicited by valproic acid. The title compounds were synthesized as their diasteriomeric ethyl esters 2b and 4b and submitted for anticonvulsant evaluation by the Antiepileptic Drug Development Program of the National Institute of Neurological and Communicative Disorders and Stroke. The results verified our hypothesis, as 4b was active in the subcutaneous pentylenetetrazol (scMet) evaluation at 30 mg/kg. Both compounds were highly toxic at 300 mg/kg.

Animals↗

PubMed1999

Quality of life and neurological illness: a review of the literature.

This article highlights some of the conceptual and methodological problems associated with quality of life (QoL) measurement in individuals with neurological illness. It is suggested that these problems have contributed to the underdeveloped status of QoL research in neurological settings. Many of the existing QoL measures that have been used, or show potential for use with individuals with neurological illness, are reviewed in terms of their theoretical basis, content, and practicality. A large proportion of these measures fail to meet adequate psychometric standards and/or have rarely been psychometrically tested. The confusion that surrounds adequate psychometric standards is discussed, and the dynamic nature of QoL is highlighted as a factor that requires further attention. Research addressing the discrepancies between proxy and patient ratings of patient QoL is also warranted. More focused research in these areas may contribute to a clearer understanding of how to assess QoL in individuals with neurological illness.

Brain Diseases↗

PubMed1996

Slow-wave activity in the spectral analysis of the electroencephalogram and volumes of hippocampus in subgroups of Alzheimer's disease patients.

This study examined patients who fulfilled the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association Work Group criteria for probable Alzheimer's disease (AD; n = 35) and controls for magnetic resonance imaging and psychometric data (n = 16) and for quantitative electroencephalogram data (n = 34). A cluster analysis performed on neuropsychological variables identified 2 AD subgroups: The AD1 group (n = 12) had impaired memory and executive functions but preserved verbal and visuospatial functions. The AD2 group (n = 23) had global impairment. The AD2 group had higher theta amplitude in the temporo-occipital, centroparietal, and frontal derivation and lower peak and mean frequency than the AD1 group or controls. Both AD groups had more severe memory deficits and clearly smaller hippocampal volumes than controls. This may implicate that the degree of damage in ascending activating systems differs in these subgroups, although the damage in the hippocampus is equal.

Aged↗

PubMed2006

A narrative therapy approach to counseling: a model for working with adolescents and adults with language-literacy deficits.

PURPOSE: Remediation efforts with adolescents and adults with language-literacy deficits (LLD) may be hindered by concomitant factors such as decreased self-esteem and self-efficacy. Despite sound linguistically based remediation practices, treatment lacking integrated counseling components may fail to achieve optimal outcomes. In this tutorial, we recount a counseling approach, specifically a narrative therapy counseling approach based on constructivist theory, to be used with adolescents and adults with LLD. METHOD: A review of the literature includes research on the use of counseling in communication disorders settings and on the application of a narrative therapy counseling approach with individuals with decreased self-esteem. The key components and steps of narrative therapy are described, and applications for use with adolescents and adults with LLD are suggested. Sample vignettes of a counseling component for a 22-year-old student with LLD who is enrolled in literacy intervention are used to illustrate some of the key points of a narrative therapy counseling approach. IMPLICATIONS: A narrative therapy counseling approach that is integrated into language-literacy remediation may be an effective way of addressing concomitant factors such as decreased self-esteem in adolescents and adults with LLD. Readers of this article are challenged to seek additional counseling training and to begin to conduct research to determine the feasibility, effectiveness, and efficacy of integrating a counseling component into speech and language therapy.

Adolescent↗

PubMed2004

The AuD program at the University at Buffalo.

The doctor of audiology (AuD) program at the University at Buffalo is summarized in this article. We begin with a description of the city of Buffalo and the University at Buffalo. This is followed by a brief history of the university and the Department of Communicative Disorders & Sciences. We then summarize the timeline and the process required to develop the AuD program. Admissions policies and prerequisites are then reviewed. We discuss the faculty active in our AuD program and present the requirements (clinical, academic, research) for the degree. The article ends with a delineation of the challenges we face, as well as a description of some of the factors that make the audiology program at the University at Buffalo unique.

Audiology↗

PubMed2001

Clinicoanatomic studies in dysarthria: review, critique, and directions for research.

More than 30 years ago, Darley, Aronson, and Brown (1969) proposed clinicoanatomic correlations for seven perceptual types of dysarthria. These correlations have not been systematically re-examined even though imaging technologies developed in recent years provide the means to do so. This review considers data from published imaging studies as well as data from selected medical interventions to evaluate the current state of knowledge that relates lesion site to the nature of a speech disturbance. Although the extant data are not sufficient to allow a complete evaluation of the seven types of dysarthria described by Darley et al., relevant information has been reported on lesions of the pyramidal pathway, extrapyramidal pathway, and cerebellum. In general, the results are best explained by an equivalence mode of brain-behavior relationship in which a type of dysarthria is associated with a lesion in one of two or more brain structures. Criteria also are proposed for future studies of clinicoanatomic relationships in neurogenic communication disorders.

Brain↗

PubMed2002

Statistical power in stuttering research: a tutorial.

The capacity to make reliable inductive statements about populations is critical for the advancement of scientific knowledge. An important contribution to that advancement of knowledge is determining that effects are either present or not present in populations. Statistical power is an important methodological qualification for any research that presents statistical results, and particularly so for research that presents null results. In this paper we describe the statistical concept of power, outline parameters of research that influence it, and demonstrate how it is calculated. With reference to selected published research, attention is drawn to the problems associated with a body of underpowered research, one being that population effects may go undetected. One way to prevent this problem is to calculate power a priori in planning research and include confidence intervals when presenting the results of research. However, it is difficult, if not impossible in many cases, to obtain high participant numbers for communication disorders of low prevalence such as stuttering. With this in mind, the paper concludes with an attempt to open discussion about ways to redress the problems associated with statistical power.

Humans↗

PubMed1978

A study of clients' perceptions of therapeutic effectiveness.

A factor-analytic investigation was conducted to determine how adult communication-disordered clients perceive variables that speech-language pathologists feel are important to effective management. One hundred sixty-two subjects representing a relatively balanced distribution of sex, age, and disorder group responded to the study from private, hospital, and university speech clinics. The results indicated that clinician demographic characteristics contribute least to clients' perceptions of therapeutic effectiveness while technical and interpersonal skills are the more essential ingredients of clinical management. Similarities between clients', clinicians', and supervisors' perceptions are considered and implications are discussed.

Adolescent↗

PubMed1987

Phonetic development in identical twins differing in auditory function.

The subjects of this report are identical (monozygotic) twin boys who differ in auditory function. One has normal hearing; the other has a profound hearing loss bilaterally. These boys offered a rare opportunity to study the effects of hearing loss on vocal development with reasonable control over environmental and genetic factors. This initial report focuses on their vocal development over the sampled ages of 8, 12, and 15 months. Acoustic-phonetic differences in the babbling of the two boys were evident in the 8-month sample (the first recording opportunity), and some differences between them became greater over the succeeding samples at 12 and 15 months. The major differences were in the formant patterns of vocalic elements; the frequency of occurrence of fricatives, affricates, and trills; histograms of syllable type; and variation in vowel usage. The data hold implications for the early identification of infants at risk for communication disorder and for the understanding of auditory-motor processes in phonetic development during infancy.

Child Language↗

PubMed1988

A new perspective in evaluating clinical effectiveness: the UWO Clinical Grading System.

To improve assessment of the performance of speech-language pathology students in clinical practicum, faculty and students in the Department of Communicative Disorders at the University of Western Ontario developed a new evaluation instrument, the UWO Clinical Grading System (UWO-CGS). This article reports on the development and field-testing of the UWO-CGS and includes estimates of the instrument's intrasupervisor and intersupervisor reliability. Results of content-related, construct-related, and criterion-related investigations are reported to support the inference that the UWO-CGS is a valid measure of the clinical effectiveness of student speech-language pathologists.

Clinical Competence↗

PubMed1977

Criteria for assessing therapy outcome in speech pathology and audiology.

Speech pathologists and audiologists function as both producers and consumers of information concerning therapy outcome. In both roles they have to know the questions that need to be answered to adequately evaluate a therapy method and the factors that have to be considered when interpreting answers to such questions. An approach (in the form of a work sheet) is described here that can be used for both identifying and systematically evaluating the validity, reliability, and generality of information regarding impacts of therapy methods on persons who have communicative disorders and for identifying additional information needed to complete such an evaluation. The approach is used to assess the impacts of a therapy method.

Evaluation Studies as Topic↗

PubMed1980

Voice initiation and termination times in stuttering and nonstuttering children.

The times needed to initiate and terminate voicing in response to series of short segments of 1000 Hz pure-tone auditory signal were studied for stuttering and nonstuttering children. The effects of random reward and nonreward on the phonatory response time also were studied. The experimental group consisted of 20 children, 11 of whom had other speech and/or language problems in addition to stuttering and nine whose only communication disorder was stuttering. The control group consisted of 20 normal-speaking children balanced with the stuttering group for sex and age. Children with speech and/or language problems in addition to stuttering were found to have significantly slower voice initiation and termination times than the normal-speaking children. The children with stuttering as the only speech and/or language problem generally did not differ significantly from the normal-speaking children in phonation times. The data suggest that whereas older stuttering children have longer phonation times than do nonstuttering children, younger stuttering children do not. Voicing times for responses following nonrewarded responses tended to be shorter than those for responses following rewarded responses for both groups.

Acoustic Stimulation↗

PubMed1986

An application of exploratory statistical methods to language pathology: analysis of the Western Aphasia Battery's Cortical Quotient in acute stroke patients. Research note.

Two simple exploratory statistical techniques, stem and leaf displays and box plots, are described and applied to the analysis of Western Aphasia Battery Cortical Quotient scores for 111 acute stroke patients. A stem and leaf display highlights the shape of a distribution of data and is useful for quickly ordering and displaying data in the form of a frequency distribution; box plots focus special attention on the tails of a distribution and are valuable for summarizing, analyzing, and comparing group data. These methods were used to determine an internal Cortical Quotient cutoff score to distinguish between normal and cognitively impaired patients. The utility of this Cortical Quotient cutoff score and the relevance of these statistical techniques to other research in communicative disorders are discussed.

Adult↗

PubMed1991

A preliminary investigation concerning the use of nasometry in identifying patients with hyponasality and/or nasal airway impairment.

A series of 76 patients referred for evaluation at the Oral-Facial and Communicative Disorders Program was studied in an attempt to determine the extent to which acoustic assessments of speech, made utilizing a Kay Elemetrics Nasometer, corresponded with clinical judgments of hyponasality and aerodynamic measurements of nasal cross-sectional area. Among the 38 adults, the sensitivity of Nasometer ratings in correctly identifying adult subjects with moderate to severe nasal airway impairment was 0.38, whereas the specificity was 0.92. Comparable analyses for the group of 38 children were not possible because of the extent to which nasal airway size varies up to the age of 15 years. Among the entire group of patients, the sensitivity and specificity of nasometry in correctly identifying the presence or absence of hyponasality was 0.48 and 0.79, respectively. However, when patients with audible nasal emission were eliminated from analysis, the sensitivity rose to 1.0 and the specificity rose to 0.85. Possible reasons for the findings obtained and their clinical significance are discussed.

Adult↗