Biomedical subjects

T L Williams

Publications and source records attributed to T L Williams.

At least 19 recordsLinked to original sources

PubMed2006

Reversible delayed posthypoxic leukoencephalopathy.

Hypoxic ischemic encephalopathy may cause early deep white matter abnormalities on MR imaging that usually progress to include gray matter and basal ganglia change. Toxic leukoencephalopathy due to heroin inhalation predominantly causes cerebellar and posterior cerebral radiologic change. Both conditions rarely present clinically and radiologically in a delayed manner with subsequent recovery. We report a case of reversible delayed posthypoxic/toxic leukoencephalopathy with no clinical or radiologic evidence of gray matter insult.

Adult↗

PubMed2003

Noninvasive ventilation in ALS: indications and effect on quality of life.

BACKGROUND: Noninvasive ventilation (NIV) probably improves survival in ALS, but the magnitude and duration of any improvement in quality of life (QoL) and the optimal criteria for initiating treatment are unclear. METHODS: QoL (Short Form-36 [SF-36], Chronic Respiratory Disease Questionnaire, Sleep Apnea Quality of Life Index) and respiratory function were assessed every 2 months and polysomnography every 4 months in 22 subjects with ALS. A trial of NIV was offered when subjects met one or more predefined criteria: orthopnea, daytime sleepiness, unrefreshing sleep, daytime hypercapnia, nocturnal desaturation, or an apnea-hypopnea index (AHI) of >10. Seventeen subjects were offered a trial of NIV; 15 accepted, and 10 continued treatment subsequently. Outcome was assessed by changes in QoL and NIV compliance (h/day). Subjects were followed to death or for at least 26 months. RESULTS: QoL domains assessing sleep-related problems and mental health improved (effect sizes 0.88 to 1.77, p < 0.05) and were maintained for 252 to 458 days. Median survival following successful initiation of NIV was 512 days, and survival and duration of QoL benefit were strongly related to NIV compliance. Vital capacity declined more slowly following initiation of NIV. Orthopnea was the best predictor of benefit from, and compliance with, NIV. Daytime hypercapnia and nocturnal desaturation also predicted benefit but were less sensitive. Sleep-related symptoms were less specific, and AHI > 10 was unhelpful. Moderate or severe bulbar weakness was associated with lower compliance and less improvement in QoL. CONCLUSIONS: NIV use was associated with improved QoL and survival. Subjects with orthopnea and preserved bulbar function showed the largest benefit.

Adult↗

PubMed2002

Non-invasive ventilation in motor neuron disease: current UK practice.

OBJECTIVE: To evaluate the clinical application of non-invasive ventilation (NIV) in motor neuron disease (MND) in the UK. METHOD: We conducted a postal survey of the current clinical practice of all consultant neurologists in the UK, with a second mailing to non-responders after 6 weeks. The principal outcome measures assessed were: 1. the percentage of patients with MND receiving NIV, 2. access to a NIV service, 3. routine monitoring of respiratory function, and 4. influence of symptoms, respiratory function, rate of disease progression, level of disability and bulbar involvement on referral for NIV. RESULTS: The response rate was 76%, 1719 new patients had been diagnosed in the preceding 12 months and a total of 2280 patients were under review. Of these, 126 were currently receiving NIV (5.5% of patients under review, estimated 2.6-3.5% of all MND patients). Most neurologists (172/265) had referred no patients for NIV in the preceding year, while three neurologists made 30% of all referrals nationally. Referral was based primarily on symptoms, and was influenced by the number of MND patients under review, level of disability, rate of disease progression and availability of a NIV service. Bulbar involvement was considered a relative contra-indication to NIV by 51% of responders. CONCLUSIONS: In the UK, few patients with MND are treated with NIV. There is marked variation in clinical practice. This may reflect uncertainty about the role of non-invasive ventilation in MND, and emphasizes the need for a randomized controlled trial to assess the impact of NIV on quality of life and survival.

Humans↗

PubMed2002

Factors influencing the evaluation of telehealth interventions: preliminary results from a qualitative study of evaluation projects in the UK.

We have carried out a qualitative study of factors that influence the evaluation of telehealth. The study concerned six telehealth projects that are being tracked over two years. In the first 12 months of the study we carried out semistructured interviews and made observations of the participants in the projects. Each case study involved 5-15 subjects, many of whom were interviewed several times. The results indicate that important issues affecting telehealth evaluation include developing and maintaining the technology, reorganization of clinical and administrative duties, professional dynamics, and the difficulty of integrating service provision and evaluation. The findings suggest that the evaluation of telehealth interventions is highly complex, and that this complexity is often underestimated in the design and conduct of evaluation studies.

Computer Communication Networks↗

PubMed2001

ClpX-mediated remodeling of mu transpososomes: selective unfolding of subunits destabilizes the entire complex.

E. coli ClpX, a member of the Clp/Hsp100 family of ATPases, remodels multicomponent complexes and facilitates ATP-dependent degradation. Here, we analyze the mechanism by which ClpX destabilizes the exceedingly stable Mu transpososome, a natural substrate for remodeling rather than degradation. We find that ClpX has the capacity to globally unfold transposase monomers, the building blocks of the transpososome. A biochemical probe for protein unfolding reveals that ClpX also unfolds MuA subunits during remodeling reactions, but that not all subunits have their structure extensively modified. In fact, direct recognition and unfolding of a single transposase subunit are sufficient for ClpX to destabilize the entire transpososome. Thus, the ability of ClpX to unfold proteins is sufficient to explain its role in both complex destabilization and ATP-dependent proteolysis.

ATPases Associated with Diverse Cellular Activitie↗

PubMed2001

Patient satisfaction with teledermatology is related to perceived quality of life.

BACKGROUND: There is a lack of good data about patient satisfaction with teledermatology and about its potential interaction with quality-of-life factors. OBJECTIVES: To assess the association between perceived skin-related quality of life and patient satisfaction with a nurse-led teledermatology service. METHODS: In a mobile nurse-led teledermatology clinic located in four inner city general practices in Manchester, the teledermatology service used digital cameras to capture and store images of skin conditions for remote diagnosis by dermatologists. One hundred and twenty-three adult patients, non-urgent dermatology referrals from primary care, completed the Dermatology Life Quality Index (DLQI) and a 15-item patient satisfaction questionnaire. RESULTS: In common with other studies of patient satisfaction, subjects reported highly favourable views of 'hotel' aspects of the service (93%) and found it 'convenient' (86%). However, 40% of patients would have preferred to have had a conventional face-to-face consultation with a dermatologist, and 17% felt unable to speak freely about their condition. Patient satisfaction with the service was related to quality of life. Patients reporting lower quality of life as measured by the DLQI were more likely to prefer a face-to-face encounter with a dermatologist (r = 0.216, P < 0.05), and to evince anxiety about being photographed (r = 0.223, P < 0.05). CONCLUSIONS: Patient acceptance and satisfaction with telemedicine services is complicated by patients' subjective health status. Telehealthcare providers need to recognize that patients with poor quality of life may want and benefit from face-to-face interaction with expert clinicians.

Adolescent↗

PubMed2001

Limitations of patient satisfaction studies in telehealthcare: a systematic review of the literature.

The objective of this study is to provide a systematic review of studies on patient satisfaction with telemedicine. The review included empirical studies that investigated patient satisfaction with that telemedicine service. The search strategy involved matching at least one of 11 'telemedicine' terms with one of 5 'satisfaction' terms. The following databases were searched: Telemedicine Information Exchange (TIE) database, MEDLINE, Science Citation Index (SCI), Social Science Citation Index (SSCI), Psycinfo, and Citation Index of Nursing and Allied Health (CINAHL). A highly structured instrument was used for data extraction. The review included 93 studies. Telepsychiatry represents the largest portion of these studies (25%), followed by multispecialty care (14%), nursing (11%), and dermatology (8%). Real-time videoconferencing was used in 88% of these studies. Only 19 (20%) included an independent control group, including 9 (10%) randomized control trial (RCT) studies. One third of studies were based on samples of less than 20 patients, and only 21% had samples of over 100 patients. Aspects of patient satisfaction most commonly assessed were: professional-patient interaction, the patient's feeling about the consultation, and technical aspects of the consultation. Only 33% of the studies included a measure of preference between telemedicine and face-to-face consultation. Almost half the studies measured only 1 or 2 dimensions of satisfaction. Reported levels of satisfaction with telemedicine are consistently greater than 80%, and frequently reported at 100%. Progression of telemedicine services from "trial" status to routine health service must be supported by improved research into patients' satisfaction with telemedicine. Further investigation of factors that influence patient acceptance of telemedicine is indicated.

Humans↗

PubMed2001

Targeting angiogenic processes by combination rofecoxib and ionizing radiation.

Tumor growth and angiogenesis are interdependent. Cyclooxygenase (COX) catalyzes the synthesis of prostaglandins from arachidonic acid. Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit COX-mediated synthesis of prostaglandins. COX-1 is constitutively expressed in a wide range of tissues, whereas COX-2 is cytokine inducible. Enhanced COX-2 expression has been attributed a key role in the development of inflammation and related processes observed in pathologically altered disease states. Two specific COX-2 inhibitors, namely rofecoxib (Vioxx) and celecoxib (Celebrex), both oral agents and U.S. Food and Drug Administration approved, have been shown preclinically and clinically to have efficacy comparable to that of NSAIDs for relief of pain and inflammation in osteoarthritis, with decreased risk of gastrointestinal damage. Little is known about how angiogenesis is affected by the combination of rofecoxib and radiation. We have evaluated the combination of rofecoxib, at various concentrations, and radiation on cytokine-induced angiogenesis in vitro. We have found that rofecoxib inhibited endothelial cell proliferation, migration, and tube formation (differentiation) at clinically relevant doses. In combination with radiation, inhibition of endothelial cell function further increased twofold. The combination of rofecoxib and radiation suggests a complementary strategy with clinical ramifications to target angiogenesis-dependent malignancies.

Angiogenesis Inhibitors↗

PubMed2001

The reliability and validity of a group-administered version of the body image assessment.

The Body Image Assessment (BIA) is a simple measure of body image disturbance. However, it has currently only been used with an individual administration format and only to assess ratings of current body size, ideal body size, and body dissatisfaction. It has also only been validated for use with women. In the current two studies, the reliability and validity of a group-administered version of the BIA procedure for both men and women that also assessed ratings of the ideal opposite sex and predictions about what the opposite sex would prefer as most attractive was examined. In the first study, results indicated good test-retest reliability for the group version for current and ideal body size and good concurrent validity with the individual administration format of the BIA. The results of the second study supported the construct and predictive validity of the group administered BIA, suggesting that it is a time-efficient alternative to the original, individually administered assessment.

Adolescent↗

PubMed2001

Mechanical properties of red and white swimming muscles as a function of the position along the body of the eel Anguilla anguilla.

The way in which muscles power steady swimming depends on a number of factors, including fibre type and recruitment, muscle strain, stimulation pattern and intensity, and the intrinsic mechanical properties of the muscle fibres. For a number of undulatory swimming fish species, in vivo studies have shown that muscles at different positions along the body are stimulated during different phases of the strain cycle. Moreover, some intrinsic contractile properties of the muscles have been found to vary according to their position along the body. We report the first results on the mechanical properties of the red and white muscles of an anguilliform swimmer, Anguilla anguilla. Small preparations (0.147-1.335 mg dry mass) were dissected from positions at fractions of 0.2, 0.4, 0.6 and 0.8 of total body length (BL). We determined the time to 50% and 100% peak force and from the last stimulus to 50% relaxation for isometric contractions; we measured the sarcomere lengths that coincided with in situ resting length. None of these quantities varied significantly with the longitudinal position from which the fibres were taken. We also measured power and work output during contractions under conditions approximating those used in vivo (cycle frequency, 1Hz; strain amplitude, +/- 10%L(0), where L(0) is the length giving maximum isometric force). During these experiments, work output was affected by stimulation phase, but did not depend on the longitudinal position in the body from which the muscles were taken. Our results indicate that red and white eel muscles have uniform properties along the body. In this respect, they differ from the muscle of most non-anguilliforms, in which muscle kinetics varies in a systematic way along the body. Uniform properties may be beneficial for anguilliform swimmers, in which the amplitude of the travelling wave can be pronounced over the entire body length.

Anguilla↗

PubMed2000

Molecular biology. Transposase team puts a headlock on DNA.

Transposable DNA elements jump from one location in the genome to another. But, the cut-and-paste molecular machinations that support this nomadic lifestyle are still being unraveled. In their Perspective, Williams and Baker at the Massachusetts Institute of Technology discuss new details of transposon relocation revealed through resolution of the structure of a transposase enzyme bound to DNA (Davies et al.).

Amino Acid Motifs↗

PubMed2000

The development and validation of Spanish versions of the State and Trait Food Cravings Questionnaires.

OBJECTIVE: We developed and tested the psychometric properties of Spanish versions of the Trait and State Food Cravings Questionnaires (FCQ-T and FCQ-S respectively). METHOD: The instruments were translated and adapted to Spanish and administered to undergraduate students from a Southern university in Spain (N = 271). The data were analyzed using confirmatory factor analysis to compare the factor structure of the English and Spanish versions of both questionnaires. RESULTS: The factors structure of both questionnaires obtained excellent fit indices across their Spanish versions with the one exception that some factors of the FCQ-S were more highly intercorrelated among the Spanish sample than the American. DISCUSSION: This study supports the conceptualization of food cravings as universal multidimensional motivational states that can be reliably measured and supports the use of the Spanish versions of the FCQ.

Adolescent↗

PubMed2000

Photoscreening for amblyogenic factors by public health personnel: the Eyecor Camera System.

OBJECTIVES: This pilot study was designed to assess the ability of a photoscreening camera to detect amblyogenic factors such as high refractive error, anisometropia, media opacities and strabismus in children, compared to the standard vision screening techniques employed by the local state public health screening personnel. METHODS: Public health personnel in Illinois used the Eyecor prototype to the current commercially available MTI PS-100 photoscreening camera (manufactured by Medical Technology Inc.) to screen 127 non-dilated subjects, ages 7 months to 20 years (mean age, 6 years), for amblyogenic factors. All participants were concurrently subjected to the "standard" vision screening employed routinely by state public health personnel. The study participants included a group of normal inner-city children and one group of special-needs children. The normal children came from both a public school and a private school. The special-needs children included a group of children from a state-run school for the deaf and hard-of-hearing and a separate group of children attending a multi-disciplinary Easter Seals clinic. RESULTS: In the population of normal children, the mean sensitivity and specificity for the observers using the Eyecor Camera system was 81% and 83% with a mean positive predictive value of 83%, and a mean negative predictive value of 55%. Standard vision screening techniques employed by public health service certified vision screeners had a sensitivity of 88%, a specificity of 91%, a positive predictive value of 67% and a negative predictive value of 97% in the same subjects. In the population of special-needs children with hearing impairment and developmental delay, the mean sensitivity and specificity for the observers using the Eyecor Camera system was 74% and 82% with a mean positive predictive value of 69% and a mean negative predictive value of 85%. Standard vision screening techniques employed by public health service certified vision screeners had a sensitivity of 100%, a specificity of 55%, a positive predictive value of 62% and a negative predictive value of 100% in the same subjects. (See Table 1) CONCLUSIONS: This study shows that the Eyecor Photoscreening Camera is useful in screening normal children for amblyogenic factors. Photoscreening was at least as effective as standard screening methodologies performed by certified vision screeners as required by state public health policy. In addition, photoscreening is particularly useful in testing those children "unscreenable" by conventional vision screening procedures.

Adolescent↗

PubMed1999

Organization and dynamics of the Mu transpososome: recombination by communication between two active sites.

Movement of transposable genetic elements requires the cleavage of each end of the element genome and the subsequent joining of these cleaved ends to a new target DNA site. During Mu transposition, these reactions are catalyzed by a tetramer of four identical transposase subunits bound to the paired Mu DNA ends. To elucidate the organization of active sites within this tetramer, the subunit providing the essential active site DDE residues for each cleavage and joining reaction was determined. We demonstrate that recombination of the two Mu DNA ends is catalyzed by two active sites, where one active site promotes both cleavage and joining of one Mu DNA end. This active site uses all three DDE residues from the subunit bound to the transposase binding site proximal to the cleavage site on the other Mu DNA end (catalysis in trans). In addition, we uncover evidence that the catalytic activity of these two active sites is coupled such that the coordinated joining of both Mu DNA ends is favored during recombination. On the basis of these results, we propose that the DNA joining stage requires a cooperative transition within the transposase-DNA complex. The cooperative utilization of active sites supplied in trans by Mu transposase provides an example of how mobile elements can ensure concomitant recombination of distant DNA sites.

Bacteriophage mu↗

PubMed1999

Low expression of GluR2 AMPA receptor subunit protein by human motor neurons.

Disturbance of glutamate neurotransmission may contribute to motor neuron injury in amyotrophic lateral sclerosis. There is evidence that human motor neurons may express a specific profile of glutamate receptors, with low or absent expression of mRNA for the GluR2 AMPA receptor subunit, which has a crucial role in controlling calcium permeability. This study, using an immunocytochemical approach with a GluR2 specific antibody, shows that human upper and lower motor neurons have a very low/absent expression of GluR2 protein, in contrast to many other neuronal groups. Thus, it is likely that human motor neurons express a high proportion of atypical, calcium permeable AMPA receptors which may contribute to selective vulnerability and may allow cell-specific modulation of the actions of glutamate.

Aged↗

PubMed1999

Association between a CYP3A4 genetic variant and clinical presentation in African-American prostate cancer patients.

Prostate cancer incidence, clinical presentation, and mortality rates vary among different ethnic groups. A genetic variant of CYP3A4, a gene involved in the oxidative deactivation of testosterone, has been associated recently with prostate cancer development in Caucasians. To further investigate this variant, we evaluated its genotype frequencies in different ethnic groups and its association with clinical presentation of prostate cancer in African Americans. CYP3A4 genotypes were assayed in healthy male Caucasian (n = 117), Hispanic (n = 121), African-American (n = 116), Chinese (n = 46), and Japanese (n = 34) volunteers using the TaqMan assay. The association between CYP3A4 genotype and prostate cancer presentation was determined in 174 affected African-American men. Genotype frequency of the CYP3A4 variant differed substantially across ethnic groups, with African Americans much more likely to carry one or two copies than any other group (two-sided P < 0.0001). Among African Americans, 46% (80 of 174) of men with prostate cancer were homozygous for the CYP3A4 variant, whereas only 28% (32 of 116) of African-American healthy volunteers were homozygous (two-sided P < 0.005). A consistent positive association was observed between being homozygous for the CYP3A4 variant in African-American prostate cancer patients and clinical characteristics. Men homozygous for the CYP3A4 variant were more likely to present with higher grade and stage of prostate cancer in a recessive model [odds ratio (OR), 1.7; 95% confidence interval (CI), 0.9-3.4]. This association was even stronger for men who were >65 years of age at diagnosis (n = 103; OR, 2.4; 95% CI, 1.1-5.4). In summary, the CYP3A4 genotype frequency in different ethnic groups broadly followed trends in prostate cancer incidence, presentation, and mortality in the United States. African-American prostate cancer patients had a higher frequency of being homozygous for the CYP3A4 variant than healthy African-American volunteers who were matched solely based on ethnicity. Among the patients, those who were homozygous for the CYP3A4 variant were more likely to present with clinically more advanced prostate cancer.

Adult↗

PubMed1997

Calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors: a molecular determinant of selective vulnerability in amyotrophic lateral sclerosis.

The cause of the selective degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) remains unexplained. One potential pathogenetic mechanism is chronic toxicity due to disturbances of the glutamatergic neurotransmitter system, mediated via alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-sensitive glutamate receptors. Functional AMPA receptors consist of various combinations of four subunits (designated GluR1-4). The GluR2 subunit is functionally dominant and renders AMPA receptors impermeable to calcium. Most native AMPA receptors in the mammalian central nervous system (CNS) contain the GluR2 subunit and are calcium impermeable. We have investigated the composition of AMPA receptors expressed on normal human spinal motor neurons by in situ hybridization to determine their likely subunit stoichiometry. Highly significant levels of mRNA were detected for the GluR1, GluR3, and GluR4 subunits. However, GluR2 subunit mRNA was not detectable in this cell group. The absence of detectable GluR2 mRNA in normal human spinal motor neurons predicts that they express calcium-permeable AMPA receptors unlike most neuronal groups in the human CNS. Expression of atypical calcium-permeable AMPA receptors by human motor neurons provides a possible mechanism whereby disturbances of glutamate neurotransmission in ALS may selectively injure this cell group.

Aged↗

PubMed1997

The calculation of frequency-shift functions for chains of coupled oscillators, with application to a network model of the lamprey locomotor pattern generator.

Chains of coupled limit-cycle oscillators are considered, in which the coupling is assumed to be weak and only between adjacent oscillators. For such a system the change in frequency of an oscillator due to the coupling can be expressed, up to first order in the coupling strength, by functions that depend only on the phase difference between the coupled oscillators. In this article a numerical algorithm is developed for the evaluation of these functions (the H-functions) in terms of a single oscillator and the interactions between coupled oscillators. The technique is applied to a connectionist model for the locomotor pattern generator in the lamprey spinal cord. An H-function so derived is compared to a function derived empirically (the C-function) from simulations of the same system. The phase lags that develop between adjacent oscillators in a simulated chain are compared with those predicted theoretically, and it is shown that coupling that is functionally "strong" is nonetheless weak enough to behave as predicted.

Animals↗