Psychometric properties of inhibitory control measures among youth with Down syndrome.

BACKGROUND: Inhibitory control measures have been commonly used when assessing individuals with Down syndrome. However, minimal attention has been devoted to evaluating the appropriateness of specific assessments for use in this population, potentially leading to erroneous conclusions. This study aimed to examine the psychometric properties of measures of inhibitory control among youth with Down syndrome. We sought to examine the feasibility, presence of floor or practice effects, test-retest reliability, convergent validity and correlations with broader developmental domains of a set of inhibitory control tasks. METHODS: A sample of 97 youth with Down syndrome aged 6 to 17 years old participated in verbal and visuospatial tasks of inhibitory control including the Cat/dog Stroop, Neuropsychological Assessment Second Edition (NEPSY-II) Statue, National Institutes of Health (NIH) Toolbox Cognition Battery (TCB) Flanker, Leiter-3 Attention Sustained, and the Test of Attentional Performance for Children (KiTAP) Go/No-go and Distractibility subtests. Youth also completed standardised assessments of cognition and language, and caregivers completed rating scales. Psychometric properties on the tasks of inhibitory control were evaluated against a priori criteria. RESULTS: Apart from demonstrating negligible practice effects, adequate psychometric properties were not observed for any inhibitory control measure within the current sample's age range. One task with low working memory demands (NEPSY-II Statue) generally had better psychometric properties than the other tasks assessed. Subgroups of participants with an IQ greater than 30 and age more than 8 years were shown to be more likely to be able to complete the inhibition tasks. CONCLUSIONS: Findings suggest better feasibility for analogue tasks rather than computerised assessments of inhibitory control. Given the weak psychometrics of several common measures, future studies are required to evaluate other inhibitory control measures, specifically those with reduced working memory demands for youth with Down syndrome. Recommendations for use of the inhibitory control tasks among youth with Down syndrome are provided.

Evaluating working memory outcome measures for children with Down syndrome.

BACKGROUND: There is a critical need for the psychometric evaluation of outcome measures to be used in clinical trials targeting cognition in Down syndrome (DS). This study examines a specific cognitive skill that is of particular importance in DS, working memory, and the psychometric properties of a set of standardised measurements to assess working memory in individuals with DS. METHODS: Ninety children and adolescents ages 6 to 18 years old with DS were assessed on a selection of verbal and visuospatial working memory subtests of standardised clinical assessments at two time points to examine feasibility, distributional qualities, test-retest reliability and convergent validity against a priori criteria. Caregivers also completed an adaptive behaviour questionnaire to address working memory subtests' associations with broader developmental functioning. RESULTS: The Stanford Binet-5 Verbal Working Memory, Differential Ability Scales-2 Recognition of Pictures, Stanford Binet-5 Nonverbal Working Memory and Wechsler Intelligence Scale for Children-5 Picture Span measures met the most psychometric criteria overall across the full age and IQ range of the study. Although Differential Ability Scales-2 Recall of Sequential Order and Differential Ability Scales-2 Recall of Digits Backward met the fewest a priori criteria, follow-up analyses suggested greater feasibility in specific age and IQ ranges. CONCLUSIONS: Several working memory measures appear to be psychometrically sound and appropriate for use in clinical trials for children with DS, especially when focusing on raw scores. However, floor effects on standard scores and feasibility of some measures were problematic. Guidelines for use of the working memory subtests with this population are provided.

Co-occurring medical and behavioural conditions in children with Down syndrome with or without ADHD symptom presentation.

BACKGROUND: Co-occurring attention deficit hyperactivity disorder (ADHD) is a challenge to characterise in the presence of other medical conditions commonly present in children with Down syndrome (DS). The current study examined differences among children with DS with or without ADHD symptomatology in terms of demographics, developmental level, co-occurring medical conditions, and parent and teacher ratings of behaviour and executive functioning. METHODS: Parents and teachers of 108 school-age children with DS provided ratings of ADHD symptoms, behaviour problems and executive functioning skills. Children with DS and ADHD symptom presentation, as identified by a scoring algorithm, were compared with those without ADHD symptom presentation on demographic characteristics, developmental level, co-occurring medical conditions and parent-report and teacher-report measures of behaviours and executive functioning. RESULTS: Sleep disorders, disruptive behaviour disorder, allergies and seizures were more common in children with DS and ADHD symptom presentation than in children without ADHD symptom presentation. After controlling for ADHD medication use, children with DS and ADHD symptom presentation had poorer performance than those without ADHD symptom presentation on parent behaviour ratings, teacher behaviour ratings and parent but not teacher ratings of executive functioning. No significant group differences in demographic characteristics or developmental level were identified. CONCLUSIONS: Higher rates of co-occurring medical conditions present in children with DS and ADHD symptom presentation support the need for thorough differential diagnoses. The different pattern of group differences between parent-report and teacher-report has implications for diagnostic practices across settings as well as for treatment.

Evolution and origin of sympatric shallow-water morphotypes of Lake Trout, Salvelinus namaycush, in Canada's Great Bear Lake.

Range expansion in north-temperate fishes subsequent to the retreat of the Wisconsinan glaciers has resulted in the rapid colonization of previously unexploited, heterogeneous habitats and, in many situations, secondary contact among conspecific lineages that were once previously isolated. Such ecological opportunity coupled with reduced competition likely promoted morphological and genetic differentiation within and among post-glacial fish populations. Discrete morphological forms existing in sympatry, for example, have now been described in many species, yet few studies have directly assessed the association between morphological and genetic variation. Morphotypes of Lake Trout, Salvelinus namaycush, are found in several large-lake systems including Great Bear Lake (GBL), Northwest Territories, Canada, where several shallow-water forms are known. Here, we assess microsatellite and mitochondrial DNA variation among four morphotypes of Lake Trout from the five distinct arms of GBL, and also from locations outside of this system to evaluate several hypotheses concerning the evolution of morphological variation in this species. Our data indicate that morphotypes of Lake Trout from GBL are genetically differentiated from one another, yet the morphotypes are still genetically more similar to one another compared with populations from outside of this system. Furthermore, our data suggest that Lake Trout colonized GBL following dispersal from a single glacial refugium (the Mississippian) and support an intra-lake model of divergence. Overall, our study provides insights into the origins of morphological and genetic variation in post-glacial populations of fishes and provides benchmarks important for monitoring Lake Trout biodiversity in a region thought to be disproportionately susceptible to impacts from climate change.

Analysis of T cell receptor beta chains in Lewis rats with experimental allergic encephalomyelitis: conserved complementarity determining region 3.

This study explores the usage of T cell antigen receptor (TCR) beta chain elements in Lewis rats with experimentally induced allergic encephalomyelitis (EAE). TCRs from 15 different T cell clones and hybridomas derived from animals immunized with myelin basic protein (MBP), and all having specificity for the 21-mer encephalitogenic fragment MBP 68-88, utilized V beta 8.2. In addition, there was a marked conservation of the first two amino acid residues of the junctional complementarity determining region 3 (CDR3) associated with the V beta 8.2 receptors. 12 of 15 contained an aspartic acid followed by serine regardless of the associated J beta element. At the nucleotide level, this conservation of AspSer residues was accomplished with few or no nongermline-encoded nucleotide (N) additions. A similar pattern of AspSer usage and N region nucleotide additions was observed in a number of V beta 8.2 isolates derived from MBP-immunized lymph nodes. In contrast, V beta 8.2 polymerase chain reaction amplified isolates from Lewis T cells activated with concanavalin A or from lymph nodes of complete Freund's adjuvant-immunized animals showed no AspSer utilization (0/31) in the CDR3, and four to nine N region nucleotide additions. We conclude from this finding that AspSer residues in the CDR3, limited N region nucleotide additions, along with V beta 8.2 sequences, contribute to TCR specificity for MBP 68-88. This raises the possibility that encephalitogenic, disease-causing T cells either represent a population that derives from late fetal life or alternatively, that they are rare cells with this particular TCR phenotype contributed to the T cell pool throughout adulthood and are selected by antigen. In either case, the CDR3 AspSer sequences as well as V beta 8.2 sequences are candidates for the receptor target structures recognized by regulator T cells in recovery from and resistance to active EAE. In this respect, a preliminary analysis of TCR utilization in three T cell clones specific for MBP 68-88 isolated from animals recovered from active EAE indicates that while all three use V beta 8.2, only one contains AspSer in the CDR3.

Rat T cell response to superantigens. I. V beta-restricted clonal deletion of rat T cells differentiating in rat-->mouse chimeras.

T cells of mice display V beta-specific reactivity for a spectrum of mouse mammary tumor virus (Mtv) antigens; confrontation with these antigens during ontogeny causes substantial "holes" in the T cell repertoire. Since endogenous Mtv antigens are rare in other species, the question arises whether V beta-specific recognition of Mtv antigens is unique to mice. To examine this question, rat T cells were allowed to differentiate from stem cells in severe combined immunodeficiency (SCID) mice. These rat-->mouse xenochimeras were prepared under a variety of conditions. The results show that rat T cells are strongly reactive to mouse Mtv antigens, both in terms of tolerogenicity and immunogenicity. In fact, the V beta specificity of rat and mouse T cells for Mtv antigens is almost indistinguishable.

Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL.

TRAIL (tumor necrosis factor [TNF]-related apoptosis-inducing ligand) is a molecule that displays potent antitumor activity against selected targets. The results presented here demonstrate that human monocytes rapidly express TRAIL, but not Fas ligand or TNF, after activation with interferon (IFN)-gamma or -alpha and acquire the ability to kill tumor cells. Monocyte-mediated tumor cell apoptosis was TRAIL specific, as it could be inhibited with soluble TRAIL receptor. Moreover, IFN stimulation caused a concomitant loss of TRAIL receptor 2 expression, which coincides with monocyte acquisition of resistance to TRAIL-mediated apoptosis. These results define a novel mechanism of monocyte-induced cell cytotoxicity that requires TRAIL, and suggest that TRAIL is a key effector molecule in antitumor activity in vivo.

The Shc adaptor protein is highly phosphorylated at conserved, twin tyrosine residues (Y239/240) that mediate protein-protein interactions.

BACKGROUND: Signal transduction initiated by a wide variety of extracellular signals involves the activation of protein-tyrosine kinases. Phosphorylated tyrosine residues in activated receptors or docking proteins then function as binding sites for the Src homology 2 (SH2) or phosphotyrosine-binding (PTB) domains of cytoplasmic signalling proteins. Shc is an adaptor protein that contains both PTB and SH2 domains and becomes phosphorylated on tyrosine in response to many different extracellular stimuli. These results have suggested that Shc is a prominent effector of protein-tyrosine kinase signalling. Thus far, only a single Shc phosphorylation site, the tyrosine at position 317 (Y317) has been identified. Phosphorylation of Y317 has been implicated in Grb2 binding and activation of the Ras pathway. RESULTS: Here, we report the identification of two major and novel Shc tyrosine phosphorylation sites, Y239 and Y240. These residues are present in the central proline-rich (CH1) region and are conserved in all isoforms of Shc. Y239/240 are co-ordinately phosphorylated by the Src protein-tyrosine kinase in vitro, and in response to epidermal growth factor stimulation or in v-src-transformed cells in vivo. Mutagenesis studies indicate that Y239/240 make an important contribution to the association of Shc with Grb2. Phosphopeptide-binding studies suggest that these two tyrosine residues may be involved in interactions with a number of cellular proteins. CONCLUSIONS: Shc is the most prominent general substrate for protein-tyrosine kinases in vivo. The identification of two novel Shc phosphorylation sites indicates that Shc has the potential to interact with multiple downstream effectors. Shc Y239/240 are highly conserved in evolution, suggesting that the phosphorylation of these residues is of fundamental importance. We propose that distinct Shc phosphorylation isomers from different signalling complexes and thereby activate separate downstream signalling cascades.

A conserved amino-terminal Shc domain binds to phosphotyrosine motifs in activated receptors and phosphopeptides.

BACKGROUND: Signal transduction by growth factor receptor protein-tyrosine kinases is generally initiated by autophosphorylation on tyrosine residues following ligand binding. Phosphotyrosines within activated receptors form binding sites for the Src homology 2 (SH2) domains of cytoplasmic signalling proteins. One such protein, Shc, is tyrosine phosphorylated in response to a large number of growth factors and cytokines. Phosphorylation of Shc on tyrosine residue Y317 allows binding to the SH2 domain of Grb2, and hence stimulation of the Ras pathway. Shc is therefore implicated as an adaptor protein able to couple normal and oncogenic protein-tyrosine kinases to Ras activation. Shc itself contains an SH2 domain at its carboxyl terminus, but the function of the amino-terminal half of the protein is unknown. RESULTS: We have found that the Shc amino-terminal region binds to a number of tyrosine-phosphorylated proteins in v-src-transformed cells. This domain also bound directly to the activated epidermal growth factor (EGF) receptor. A phosphotyrosine (pY)-containing peptide modeled after the Shc-binding site in polyoma middle T antigen (LLSNPTpYSVMRSK) was able to compete efficiently with the activated EGF receptor for binding to the Shc amino terminus. This competition was dependent on phosphorylation of the tyrosine residue within the peptide, and was abrogated by deletion of the leucine residue at position -5. The Shc amino-terminal domain also bound to the autophosphorylated nerve growth factor receptor (Trk), but bound significantly less well to a mutant receptor in which tyrosine Y490 in the receptor's Shc-binding site had been substituted by phenylalanine. CONCLUSION: These data implicate the amino-terminal region of Shc in binding to activated receptors and other tyrosine-phosphorylated proteins. Binding appears to be specific for phosphorylated tyrosine residues within the sequence NPXpY, which is conserved in many Shc-binding sites. The Shc amino-terminal region bears only very limited sequence identify to known SH2 domains, suggesting that it represents a new class of phosphotyrosine-binding modules. Consistent with this view, the amino-terminal Shc domain is highly conserved in a Drosophila Shc homologue. Binding of Shc to activated receptors through its amino terminus could leave the carboxy-terminal SH2 domain free for other interactions. In this way, Shc may function as an adaptor protein to bring two tyrosine-phosphorylated proteins together.

GJB2 mutations and additional disabilities in a pediatric cochlear implant population.

BACKGROUND: Children with severe to profound sensorineural hearing loss due to GJB2 mutations have often been deemed good cochlear implant candidates. Studies on children with GJB2 mutations and cochlear implants have typically excluded children with additional disabilities. OBJECTIVE: To investigate the presence of additional disabilities among children with and without GJB2 mutations in a cochlear implant population. METHODS: A retrospective chart review was performed of children with non-syndromic sensorineural hearing loss (SNHL) who received a cochlear implant between 1993 and 2004. RESULTS: Among 108 children within the cochlear implant database; 46 patients met the inclusion criteria of idiopathic non-syndromic hearing loss. Sixteen children had GJB2 mutations, 12 were GJB2 negative, and 17 did not receive GJB2 testing but had no other identifiable etiology or risk factor contributing to hearing loss. The proportion of children with additional disabilities that would affect either pre-operative assessments or post-operative results in the GJB2 positive group was 44% compared to 33% of children in the GJB2 negative. Additional disabilities were present in 41% of the children who did not receive GJB2 testing. The disabilities in the GJB2 positive group included specific learning disability, apraxia, epileptiform aphasia, attention deficit disorder, global developmental delay, and gross motor delay. The GJB2 negative and those children not receiving GJB2 testing had motor delays, language delay, autism, specific learning disability, and attention deficit disorder. The proportion of children with at least 6 months CI use who relied on oral communication was 62% in the GJB2 positive group, 66% in the GJB2 negative group, and 38% in the untested group. A majority of the genetic alleles were 35delG (81%) and 10 of 16 (63%) patients with GJB2 mutations were homozygous 35delG. The rate of developmental diagnoses was similar in patients with homozygous GJB2 compared to compound heterozygous genotypes. CONCLUSIONS: The presence of biallelic GJB2 mutations does not rule out non-hearing related disorders that can have an effect on speech, language and learning. Forty-four percent of children with GJB2 mutations had other conditions that could directly affect pre-implant evaluation and post-implant performance. This rate is similar to the reported prevalence among the overall population of children with hearing loss. All children should have a comprehensive evaluation of development and behavior regardless of the etiology of hearing loss.

Re-engineering the target specificity of the insulin receptor by modification of a PTB domain binding site.

Shc and IRS-1 (and their relatives) are cytoplasmic docking proteins that possess phosphotyrosine-binding (PTB) domains, through which they bind specific activated receptor tyrosine kinases (RTK). The subsequent phosphorylation of Shc or IRS-1 creates binding sites for the SH2 domains of multiple signaling proteins, leading to the activation of intracellular biochemical pathways. The PTB domains of Shc and IRS-1 both recognize autophosphorylation sites in RTKs with the consensus sequence NPXpY, but show distinct abilities to bind stably to RTKs such as the TrkA nerve growth factor receptor and the insulin receptor. In vitro analysis has suggested that residues N-terminal to the NPXpY motif may determine the affinity with which phosphopeptide ligands are recognized by the Shc and IRS-1 PTB domains. Unlike IRS-1, the Shc PTB domain binds poorly to the insulin-receptor (IR) beta subunit in vitro, owing to its low affinity for the NPXpY autophosphorylation site at Tyr 960 of the IR. As a consequence, Shc does not bind stably to the activated IR in cells. We show that substitution of Ser 955, five residues N-terminal to the Tyr 960 autophosphorylation site (the -5 position), with Ile alters the target specificity of the IR such that it stably associates with Shc in insulin-stimulated cells. A triple substitution of the -5, -8 and -9 residues relative to Tyr 960 of the IR to the corresponding amino acids found in the Shc PTB domain binding site of TrkA results in even stronger binding of the IR to Shc in vivo. The variant IRs with enhanced ability to bind Shc showed an increased ability to activate the MAPK pathway in response to insulin stimulation. These results demonstrate that subtle differences in residues N-terminal to NPXpY autophosphorylation sites determine the ability of RTKs to bind specific PTB domain proteins in vivo, and thus modify the signaling properties of activated receptors.

Estrogen-related receptor alpha 1 functionally binds as a monomer to extended half-site sequences including ones contained within estrogen-response elements.

The human estrogen-related receptor alpha 1 (hERR alpha 1) is an orphan member of the steroid/thyroid hormone receptor superfamily. A cDNA encoding this protein was originally isolated on the basis of sequence similarity in its DNA-binding domain with estrogen receptor alpha (ER alpha). Previously, we reported the purification of hERR alpha 1 from HeLa cell nuclear extracts on the basis of its ability to bind two sites in the late promoter of simian virus 40 (SV40). We have now determined the primary structure and the DNA and protein binding specificities of hERR alpha 1 and developed in vivo and in vitro assays for its functional activities. hERR alpha 1 was found to bind as a monomer, with a high-affinity binding site containing the extended half-site sequence 5'-TCAAG-GTCA-3'. Binding sites for hERR alpha 1 were identified in many cellular promoters, including some that were previously shown to function as estrogen-response elements (EREs). hERR alpha 1 was shown to function as a sequence-specific repressor of the SV40 late promoter in both cell culture and cell-free transcription systems. It was also shown to interact with both ER alpha and the transcription factor TFIIB by direct protein-protein contacts. Thus, hERR alpha 1 may play a role in the response of some genes to estrogen via heterodimerization with ERs or competition with ERs for binding to EREs.

Genomics in the real world.

The term genomics has evolved into a catch-all term for a variety of information intensive biological methodologies. While the promise of genomics in the bio/pharmaceutical industry is great, its impact on the drug discovery pipeline has not yet been realized, excluding a few notable exceptions. As companies acquire several years of experience in working with genomic data, it is likely that the impact on the discovery process will slowly emerge as we learn to integrate these new technologies into individual discovery programs. It is clear that extracting novel biologically valid targets targets from exponentially growing amounts of sequence data requires time and considerable investment in biological research infrastructure. In order to accelerate the process of target validation, a variety of functional genomics technologies are also being developed to try to predict the effect of inhibitory compounds in advance of development. Resources spent on early stage exploratory efforts such as these can pay off by improving the success rate for screening and medicinal chemistry.

Ipecac administration in children younger than 1 year of age.

The efficacy of ipecac syrup in the induction of emesis and safety of its administration was studied in 105 poison-exposed infants 6 through 11 months of age (study subjects) and compared prospectively with 302 poison-exposed infants and children 12 through 35 months of age who served as age controls. Of the 105 study subjects 101 (96.2%) vomited. The failure of ipecac to induce emesis in six patients (four of 105 study subjects two of 302 age control subjects) is comparable with ipecac failure rates reported elsewhere. The frequency of side effects caused by ipecac syrup did not differ between study and control subjects. There were no serious medical complications resulting from the administration of ipecac syrup. When not readily available at home, ipecac administration was delayed an additional 21.8 minutes if obtained from a pharmacy and 38.4 minutes if obtained from an emergency department. Because of the time delay and the increased health care cost, home rather than emergency department administration of ipecac should be advised. These data demonstrate that ipecac syrup effectively induces emesis and is safe for home administration to poisoned infants 6 to 11 months old.

Infection control practices in the home: a survey of households of HIV-infected persons with hemophilia.

OBJECTIVE: To assess infection control practices and risk for human immunodeficiency virus (HIV) transmission in households where home infusion for hemophilia is used. DESIGN: Cross-sectional prospective survey from 1992 through 1994. SETTING: Hemophilia treatment centers. PARTICIPANTS: Human immunodeficiency virus (HIV)-infected persons with hemophilia who receive home infusions of clotting factor concentrate and their household members. MAIN OUTCOME MEASURES: Frequency of specific infection control practices in the home and the risk of HIV transmission to household members. RESULTS: We surveyed 235 persons from 75 families (79 HIV-infected persons with hemophilia and 156 household members) about infection control practices in the home. Forty-eight percent of household members surveyed helped with the infusion process. Of 74 members who assisted with infusion, 13 (18%) had sustained a needlestick injury, 11 of whom were injured during the past year. One hundred fifty household members tested for antibody to HIV were antibody negative. These household members had a total of 903 person-years of contact after HIV was diagnosed in the index case. Household members' adherence to recommended infection control measures was highest for washing hands after cleaning up infusion equipment and waste, and for using sharps disposal containers. Adherence was lowest for wearing gloves when helping with infusions and proper disposal of bloody waste from the infusion. CONCLUSIONS: No HIV transmission was found among persons living with HIV-infected persons with hemophilia, although there was a high rate of needlestick injuries during home infusion. Because persons who assisted with infusions often did not wear gloves and many households did not dispose of bloody waste properly, hemophilia treatment center personnel should emphasize these areas when training for home infusion. Adherence to appropriate infection control practices should help to keep the risk of HIV transmission in households extremely low.

Deception and detection in psychiatric diagnosis.

Deception is ubiquitous in all communication and relationships. It can be conscious, unconscious, or both. It is present in all psychiatric diagnoses as alterations of history, symptom fabrication, symptom enhancement or minimization, and noncompliance with treatment recommendations. We are born better deceivers than we are detectors and untrained intuition may result in very unreliable discrimination. In order to improve our ability to distinguish fact from fiction, the diagnostician must attend to clues in the patient's history and physical and mental status examinations. Laboratory examination, psychological testing, and polygraphy also can be useful adjuncts in detection; however, the first step is always suspicion.

Attitudes and practices of hemophilia care providers involved in HIV risk-reduction counseling.

Hemophilia physicians, nurses, and social workers attending a national conference were asked to complete a questionnaire assessing their attitudes and practices regarding HIV risk-reduction counseling. All of the 150 respondents reported recommending the use of condoms to their clients, but only two-thirds felt comfortable demonstrating a condom, while fewer could explain condom choices or how to make safe sex more pleasurable. Less than half questioned their clients about history of STDs, sexual practices, or level of sexual satisfaction. Those who devoted 50 percent or more time to HIV risk-reduction efforts reported being more complete in their assessment and more comfortable in their counseling role. Providers claimed it would help if they had more time (84%) and better skills (64%, especially nurses) for this practice. Because HIV prevention services in hemophilia are delivered by a team, further studies are required to determine the aggregate impact of their intervention on the client.

Assessment of quadriceps muscle performance by a hand-held dynamometer and an isokinetic dynamometer.

Assessment of muscle performance is an integral component of patient evaluation. The primary purposes of this study were to examine the relationship between isokinetic dynamometer isokinetic peak force values and hand-held dynamometer isometric peak force values when assessing quadriceps muscle performance in subjects with orthopaedic knee dysfunctions (N = 21) and to test for differences in muscle performance between injured and noninjured lower extremities using a hand-held dynamometer and an isokinetic dynamometer. An analysis of variance was used to compare injured and noninjured extremities for both testing devices. A Pearson product moment correlation was used to examine the relationship between the hand-held dynamometer and isokinetic dynamometer values. No significant difference between extremities at 0 degrees (p = 0.1224) or 60 degrees (p = 0.8267) was revealed when testing with the hand-held dynamometer. The isokinetic dynamometer, however, revealed a significant difference between extremities at 60 degrees/sec (p = 0.0041). Correlations between the two devices were significant, ranging from r = 0.57 to 0.80. We concluded that these correlations were misleading because more force was generated by the quadriceps muscles tested than a tester of average strength could resist. Further research is needed to validate the use of the hand-held dynamometer by a tester of average strength.