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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 325 records · Page 18Linked to original sources
PubMed2000

Kinematic correlates of speaking rate changes in stuttering and normally fluent adults.

Articulatory kinematics were analyzed to determine if adults who stutter are generally poorer at speech movement pattern generation and if changing speech rate affects their stability in the same way that it affects normally fluent controls. Adults who stutter (n = 14) and a matched group of controls produced fluent repetitions of a simple phrase at normal, slow, and fast rates. A composite index of spatiotemporal stability (STI), as well as independent measures of timing and spatial variability, revealed that adults who stutter can operate within normal movement parameter ranges under low-demand speaking conditions. However, some of the stuttering participants showed evidence of abnormal instability even when repeating a simple utterance at habitual rate. Also, measures of relative timing indicated that adults who stutter, unlike their matched controls, are not better timers at habitual vs. nonpreferred speech rates. Overall, the results suggest that the kinematic characteristics of the fluent speech of adults who stutter generally overlap that of normally fluent speakers; however, subtle differences in kinematic parameters are interpreted to reveal their susceptibility to speech motor breakdown when performance demands increase.

Adult↗
PubMed2000

Influences of length and syntactic complexity on the speech motor stability of the fluent speech of adults who stutter.

The purpose of the present study was to investigate the impact of utterance length and syntactic complexity on the speech motor stability of adults who stutter. Lower lip movement was recorded from 8 adults who stutter and 8 normally fluent controls. They produced a target phrase in isolation (baseline condition) and the same phrase embedded in utterances of increased length and/or increased syntactic complexity. The spatiotemporal index (STI) was used to quantify the stability of lower lip movements across multiple repetitions of the target phrase. Results indicated: (a) Adults who stutter demonstrated higher overall STI values than normally fluent adults across all experimental conditions, indicating decreased speech motor stability; (b) the speech motor stability of normally fluent adults was not affected by increasing syntactic complexity, but the speech motor stability of adults who stutter decreased when the stimuli were more complex; (c) increasing the length of the target utterance (without increasing syntactic complexity) did not affect the speech motor stability of either speaker group. These results indicate that language formulation processes may affect speech production processes and that the speech motor systems of adults who stutter may be especially susceptible to the linguistic demands required to produce a more complex utterance. The present findings, therefore, support the hypothesis that linguistic complexity is one factor that contributes to the disruptions of speech motor stability characteristic of stuttering.

Adult↗
PubMed2000

Influences of utterance length and complexity on speech motor performance in children and adults.

The possible influences of utterance length and complexity on speech motor performance were examined by assessing the effects of increased processing demands on articulatory movement stability. Eight 5-year-old children and 8 young adults repeated a 6-syllable phrase in isolation (baseline condition) and embedded in sentences of low and high syntactic complexity. Lower lip movements for the target phrase were analyzed to produce the spatiotemporal index (STI), an index that reflects the stability of lip movement over 10 repetitions of the phrase. It was predicted that movement stability would be lower (reflected by higher values of the STI) for the phrase when it was spoken embedded in complex sentences and that, compared to adults, children's movement output would be more negatively affected by increased processing demands. The STI was significantly increased for the phrase spoken in the complex sentences compared to the baseline condition, and STIs of the children were consistently higher than those of the adults across conditions. These findings provide novel evidence that speech motor planning, execution, or both are affected by processes often considered to be relatively remote from the motor output stage.

Adult↗
PubMed2000

Respiratory control in stuttering speakers: evidence from respiratory high-frequency oscillations.

This study tested the hypothesis that, in stuttering speakers, relations between the neural control systems for speech and life support, or metabolic breathing, may differ from relations previously observed in normally fluent subjects. Bilaterally coherent high-frequency oscillations in inspiratory-related EMGs, measured as maximum coherence in the frequency band of 60-110 Hz (MC-HFO), were used as indicators of participation by the brainstem controller for metabolic breathing in 10 normally fluent and 10 stuttering speakers. In all controls and most stuttering subjects, MC-HFO for speech was higher than or comparable to MC-HFO for deep breathing. For 4 stuttering subjects, higher MC-HFO was observed for speech than for deep breathing. Comparison of deep breathing to a speechlike breathing task yielded similar results. No relationship between MC-HFO during speech and severity of disfluency was observed. We conclude that in some stuttering speakers, the relations between respiratory controllers are atypical, but that high participation by the HFO-producing circuitry in the brainstem during speech is not sufficient to disrupt fluency.

Adult↗
PubMed2000

Pathology characteristics that optimize outcome prediction of a breast screening trial.

The ability of pathology characteristics to predict outcome was tested with the 1029 cancers accumulated in the Edinburgh Randomized Trial of breast screening after 14 years follow-up. The majority (55.7%) were in the screening arm, which also had more operable cases (81.3% vs 62.2%); the reduction in the proportion of inoperable breast cancers in a UK female population invited to mammographic screening is a notable effect of the trial. In the 691 operable invasive cases the size, histological type, grade, node status and node number group individually showed highly significant (P<0.001) association with survival. In multivariate analysis the Nottingham Prognostic Index (NPI) derived from these features showed highly significant association with survival (P<0.001). However, when first adjusted for NPI, combined addition of pathological size in 6 categories and histological type as special or not had an independent association with survival that was statistically firmly based (P<0.001). For operable breast cancer the gains are in smaller sizes, better histological features, and higher proportion node negative. The weighting factors applied to pathology indicators of survival in the NPI are not optimal for a population included in a trial of screening. In particular, a linear trend of the index with pathological size is not appropriate. Inclusion of histological type as special or not improves the index further.

Analysis of Variance↗
PubMed2000

Abciximab provides cost-effective survival advantage in high-volume interventional practice.

BACKGROUND: Placebo-controlled randomized trials of platelet glycoprotein (GP) IIb/IIIa blockade during percutaneous coronary intervention have demonstrated efficacy of these agents for reducing the risk of periprocedural ischemic events. However, cost-effectiveness of this adjunctive pharmacotherapy has been scrutinized. Extrapolation of cost-efficacy observations from clinical trials to "real world" interventional practice is problematic. METHODS: Consecutive percutaneous coronary interventions (n = 1472) performed by Ohio Heart Health Center operators at The Christ Hospital, Cincinnati, Ohio, in 1997 were analyzed for procedural and long-term (6-month) outcomes and charges. Observations on cost and efficacy (survival) were adjusted for nonrandomized abciximab allocation by means of "propensity scoring" methods. RESULTS: Abciximab therapy was associated with a survival advantage to 6 months after percutaneous coronary intervention. The average reduction in mortality rate at 6 months was 3.4% (unadjusted) and 4.9% when adjusted for nonrandomization. The average charge increment to 6 months was $1512 (unadjusted) and $950 when adjusted for nonrandomization. Patients deriving the greatest reduction in mortality rates also had a reduction in total cardiovascular charges to 6 months. Distinguishing demographics of this population included multivessel coronary intervention, coronary stent deployment, intervention within 1 week of myocardial infarction, and lower left ventricular ejection fraction. The average cost per life-year gained in this study was $2875 for all patients (unadjusted) and $1243 when adjusted for nonrandomization. CONCLUSIONS: Abciximab provides a cost-effective survival advantage in high-volume interventional practice that compares favorably with currently accepted standards. Clinical and procedural demographics associated with increased cost-effectiveness included multivessel coronary intervention, stent deployment, recent (<1 week) myocardial infarction, and impaired left ventricular function.

Abciximab↗
PubMed2000

Vascular endothelial growth factor and basic fibroblast growth factor are found in resolving venous thrombi.

OBJECTIVE: Resolution of venous thrombi is accompanied by an ingrowth of capillaries, which appears to be analogous to angiogenesis in other tissues. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are major regulators of angiogenesis. The aim of this study was to determine the temporal changes and the location of VEGF and bFGF expression in a rat model of venous thrombus resolution. DESIGN AND METHODS: Thrombi were induced in the inferior venae cavae of rats by creating a stenosis to reduce blood flow by 80% to 90%. Thrombi, adjacent inferior vena cava wall, and systemic blood were collected at 1, 3, 7, 14, 21, and 28 days after thrombus generation (n = 9). Sham operations were performed (n = 5), and blood was collected at 1, 3, and 7 days. VEGF and bFGF were measured with specific immunoassays, and levels in tissues were expressed as picogram per milligram soluble protein. Tissues from two animals that were humanely killed 7 days after thrombus formation were prepared for histological examination. Immunohistochemistry was performed by the use of antibodies against VEGF, bFGF, and ED-1 (a monocyte/macrophage marker). RESULTS: Laminated thrombi were reliably produced with a median weight at 1 day of 39 mg (range, 23-63 mg). There was a significant increase in thrombus VEGF concentration between 1 day (median, 247; range, 0-514) and 7 days (median, 556; range, 254-1741) (P =.02). There was no difference between the seventh day and subsequent days. There was a positive linear correlation between thrombus bFGF concentration and time (R = 0.74, P <.0001), with a more than 300-fold increase in bFGF concentration over the 28 days of the study. VEGF and bFGF concentrations in the adjacent vena caval wall did not change significantly with time. The serum VEGF was significantly raised at 1 day (median, 5520 pg/mL; range, 4040-7912 pg/mL) and 3 days (median, 3880 pg/mL; range, 2564-7232 pg/mL) compared with 7 days (median, 1790 pg/mL; range, 232-3228 pg/mL) (P <.0001). Similar changes in the serum VEGF also developed in the sham-operated animals. The serum bFGF (day 1 median, 15.5 pg/mL; range, 1-42 pg/mL) did not change with time. Immunohistochemistry showed that the VEGF antigen was localized to monocytes, endothelial cells, and spindle-shaped cells within the thrombus. The bFGF antigen was localized to mononuclear cells and spindle-shaped cells and was also present in the extracellular matrix. CONCLUSION: VEGF and bFGF are found in organizing thrombi and have characteristic temporal expression patterns, which suggest that they have a role in thrombus resolution. Augmenting angiogenic growth factor expression may enhance thrombus recanalization, thus reducing long-term complications.

Animals↗
PubMed2000

Effects of upper respiratory tract illnesses on mood and performance over the working day.

The present study examined whether volunteers with common colds showed impairments in objective and subjective indicators of alertness over the course of the working day. All the volunteers (n = 21) were tested when healthy to provide baseline data for simple and choice reaction time tasks, visual search tasks and ratings of mood. These measures were taken before work (08.30 hours), at lunchtime (13.00) and after work (17.30). When participants developed a cold (n = 6) they repeated the procedure. Volunteers (n = 15) who remained healthy were recalled as controls and also repeated the procedures. The results showed that those with colds had significantly slower simple and choice reaction times, and felt less alert, more tense and less sociable. The effects of having a cold on simple reaction time, alertness and anxiety increased over the day. This extends earlier research and shows that some of the effects of upper respiratory tract illnesses on mood and performance will depend on when assessments are made. These results also imply that performance and well-being at work will be impaired by upper respiratory tract illnesses.

Adult↗
PubMed2000

After-effects of the common cold on mood and performance.

The present study examined whether volunteers who had recently had common colds showed impairments in mood and performance in the weeks following the illness. All volunteers (n = 24) were tested when healthy to provide baseline data for simple and choice reaction time tasks, attention and memory tasks and ratings of mood. When participants developed a cold (n = 13) they returned to the laboratory so that the illness could be verified. When they were symptom free they returned to the laboratory and repeated the procedure. They then completed the study with a final session 1 week later. Volunteers (n = 11) who remained healthy over 10 weeks were recalled as controls and also repeated the procedures. The results showed that those who had recently had colds showed few impairments in mental performance and mood. Taken together with the results of previous studies, this suggests that after-effects of viral infection are largely restricted to severe illnesses such as infectious mononucleosis and influenza. After-effects of colds may occur but these probably reflect poor learning at the time of the illness.

Adolescent↗
PubMed2000

The effect of changing the excreta moisture of caged laying hens on the excreta and microbial contamination of their egg shells.

1. An experiment that included 1440 caged laying hens in 24 experimental units was conducted to determine the effect of differences in excreta moisture on the proportion of dirty eggs and the microbial contamination of eggs that were ostensibly uncontaminated by excreta. Excreta moisture contents were changed by giving the hens diets that contained 4 different concentrations of sodium. 2. Diets containing 1.6, 5, 10 or 15 g/kg dietary sodium were fed ad libitum to 1140 laying hens for a 12-week feeding period. A sample of excreta was collected from each experimental unit each week and its moisture content determined. All eggs produced were classified as clean or dirty according to the European Community Egg Marketing Regulations. A sample of eggs were collected from each experimental unit on 4 separate occasions in the last 4 weeks of the feeding period and the total bacterial numbers on ostensibly clean egg shells were determined. 3. Increasing dietary sodium concentration gave linear (P<0.01) increases in excreta moisture. Each 100 g/kg increase in excreta moisture increased (P<0.001) dirty egg numbers by 0.52% of the total eggs produced. Increasing excreta moisture gave a linear increase (P<0.001) in the (log-transformed) numbers of microorganisms that contaminated ostensibly clean egg shells.

Animals↗
PubMed2000

Effect of excess dietary sodium, potassium, calcium and phosphorus on excreta moisture of laying hens.

1. Four experiments were conducted to investigate the effects of dietary concentrations of sodium, potassium, calcium or phosphate on the water intake and excreta moisture of laying hens. A fifth experiment examined the effect on these variables of increasing amounts of 2 different sodium salts (chloride or bicarbonate) and the interactions with 2 levels of dietary phosphorus. 2. All experiments involved individually caged laying hens fed on diets varying in 1 or 2 minerals in replacement for washed sand. The experimental diets contained mineral concentrations that either met or exceeded the expected requirement of the hens. The diets were given for a 7 or 8 d feeding period and food and water intakes were measured and excreta were collected for the last 48 h of each feeding period. These data were corrected for evaporative water loss to the environment during the collection period. 3. Increasing dietary concentrations of sodium, potassium or phosphorus gave linear increases (P<0.001) in the water intake of the laying hens and linear increases (P<0.01) in the moisture content of their excreta. Each 1 g/kg increase in dietary mineral increased the moisture content of the excreta by 9.04 (+/- 1.57), 11.95 (+/- 2.02) and 5.59 (+/- 0.31) g/kg (+/- standard error) for sodium, potassium and phosphorus, respectively. Increasing concentrations of dietary calcium did not significantly affect the water intakes or excreta moisture levels of the laying hens. 4. The fifth experiment showed that, although there was a sodium x phosphorus interaction (P<0.05), the effects of the 2 mineral additions were approximately additive. There were no significant differences (P>0.05) in water intakes or excreta moisture contents due to the 2 different sodium salts (chloride or bicarbonate).

Animal Feed↗
PubMed2000

Links between cell-surface events involving redox-active copper and gene regulation in the hemopexin heme transport system.

Heme is considered to play an instrumental role in the pathology of hemolysis, trauma, and reperfusion following ischemia. However, data are sparse and experimental models are required. The transport of heme by hemopexin to tissues is a specific, membrane receptor-mediated process. Hemopexin recycles after endocytosis like transferrin. Heme oxygenase-1 (HO-1), transferrin, the transferrin receptor, and ferritin are regulated by heme-hemopexin. Genes that encode proteins important for cellular defenses against oxidative stress, such as the cysteine-rich metallothioneins (MTs), are also activated by hemopexin, as are proteins that regulate cell cycle control including p21WAF1 and the tumor suppressor p53. The hemopexin system is being investigated to establish how intracellular events are affected by signal(s) from the plasma membrane due to hemopexin receptor occupancy and heme transport. A transient oxidative modification of proteins, shown by carbonyl production, takes place. Redox processes at the cell surface, which generate cuprous ions, are involved in the regulation of the MT-1 and HO-1 genes by heme-hemopexin before heme catabolism and intracellular release of iron. The "redox-sensitive" transcription factors activated by the hemopexin system include c- Jun, RelA/NFkappaB and MTF-1. The specific copper chelator bathocuproine disulfonate prevents carbonyl production, the nuclear translocation of MTF-1, and the induction of MT-1 revealing a novel, pivotal role for copper in the hemopexin system. In addition, surface redox-active copper is the first link shown for the concomitant regulation of HO-1 and MT-1 and is required for the activation of the amino-terminal c-Jun kinase (JNK) by heme-hemopexin.

Animals↗
PubMed2000

Role for copper in transient oxidation and nuclear translocation of MTF-1, but not of NF-kappa B, by the heme-hemopexin transport system.

Heme-hemopexin (2-10 microM) is used as a model for intravenous heme released in trauma, stroke, and ischemia-reperfusion. A transient increase in cellular protein oxidation occurs during receptor-mediated heme transport from hemopexin which is inhibited by the nonpermeable Cu(I) chelator, bathocuproinedisulfonate. Thus, participation of surface redox process involving Cu(I) generation are proposed to be linked to the induction of the protective proteins heme oxygenase-1 (HO-1) and metallothionein-1 (MT-1) by heme-hemopexin. The region (-153 to -42) in the proximal promoter of the mouse MT-1 gene responds to heme- and CoPP-hemopexin in transient transfection assays and contains metal-responsive elements for MTF-1 and an antioxidant-responsive element (ARE) overlapping a GC-rich E-box to which USF-1 and -2 bind. No decreases in DNA binding of the diamide-oxidation sensitive USF-1 and -2 occur upon exposure of cells to heme-hemopexin. MTF-1 and the ARE-binding proteins are relatively resistant to diamide oxidation and are induced approximately eight- and two-fold, respectively, by heme-hemopexin. BCDS prevents the nuclear translocation of MTF-1 by both heme- and CoPP-hemopexin complexes as well as MT-1 mRNA induction by CoPP-hemopexin. Thus, copper is needed for the surface oxidation events and yet the nuclear translocation of MTF-1 in response to hemopexin occurs via copper, probably Cu(I),-dependent signaling cascades from the hemopexin receptor rather than the oxidation per se.

Animals↗
PubMed2000

Cell-surface events for metallothionein-1 and heme oxygenase-1 regulation by the hemopexin-heme transport system.

A model has been developed for the hemopexin receptor-mediated heme transport system based on iron uptake in yeast. Two steps are required: reduction followed by oxidation by a multi-copper-oxidase. Furthermore, in the hemopexin system, the surface redox events have been linked with gene regulation. The impermeable Cu(I) chelator bathocuproinedisulfonate (BCDS) is shown here to abrogate heme oxygenase-1 (HO-1) mRNA induction by heme-hemopexin. A role for Cu(I) in the regulation of HO-1 and MT-1 (Sung et al., 1999) by hemopexin supports the participation of electron transport processes at the cell surface as does competition by the reductase activator, ferric citrate, which inhibits the induction of MT-1 and HO-1 mRNA by heme-hemopexin. There is a key role for the hemopexin receptor because neither ferric citrate nor iron-transferrin alone regulates MT-1 or HO-1. Cell-surface copper is the first molecule to link the concomitant regulation of HO-1 and MT-1 by the hemopexin receptor. In addition, cytochrome b5 and cytochrome b5 reductase are implicated here in the response of cells to heme-hemopexin. Reduction of one or more electron donors of the reductase and oxidation of the electron acceptor, b5 heme, leads to gene regulation, but only when heme-hemopexin is bound to its receptor. Protein kinase cascades, including JNK, are activated by the hemopexin receptor itself upon ligand binding but are modulated by a Cu(I)-dependent process likely to be heme uptake.

Animals↗
PubMed2000

Myeloablative chemotherapy for recurrent aggressive oligodendroglioma.

The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving aggressively at recurrence were eligible for this study. Only complete responders or major partial responders (75 % reduction in tumor size) to induction chemotherapy--either intensive-dose procarbazine, lomustine, and vincristine or cisplatin plus etoposide-could receive high-dose thiotepa (300 mg/m2/day for 3 days) followed by hematopoietic reconstitution using either bone marrow or peripheral blood stem cells. Thirty-eight patients began induction chemotherapy and 20 (10 men, 10 women; median age 46 years; median Karnofsky score 80) received high-dose thiotepa. For the high-dose group, the median event-free, progression-free, and overall survival times from recurrence were 17, 20, and 49 months, respectively. Tumor control in excess of 2 years was observed in 6 patients (30%). Four patients (20%) are alive and tumor free 27 to 77 months (median, 42 months) from the start of induction therapy; however, fatal treatment-related toxicities also occurred in 4 patients (20%). Three patients died as a result of a progressive encephalopathy which, in 2 instances, was accompanied by a wasting syndrome; 1 patient died as a consequence of an intracerebral (intratumoral) hemorrhage. Fatal toxicities occurred in patients with pretreatment Karnofsky scores of 60 or 70. High-dose thiotepa to consolidate response was a disappointing treatment strategy for patients with recurrent aggressive oligodendroglial neoplasms, although several patients had durable responses. Moreover, as prescribed, high-dose thiotepa had significant toxic effects in previously irradiated patients, especially those with poorer performance status.

Adult↗
PubMed2000

The scale of perceived occupational stress.

This article reviews previous research on the scale of occupational stress and describes in detail the Bristol Stress and Health at Work study. This study had three main aims: firstly, to determine the scale and severity of occupational stress in a random population sample; secondly, to distinguish the effects of stress at work from those of stress in general life; and finally, to determine whether objective indicators of health status and performance efficiency were related to perceived occupational stress. These aims were investigated by conducting an epidemiological survey of 17,000 randomly selected people from the Bristol electoral register, a follow-up survey 12 months later, and detailed investigation of a cohort from the original sample. The results revealed that approximately 20% of the sample reported that they had very high or extremely high levels of stress at work. This effect was reliable over time, related to potentially stressful working conditions and associated with impaired physical and mental health. The effects of occupational stress could not be attributed to life stress or negative affectivity. The cohort study also suggested that high levels of occupational stress may influence physiology and mental performance. The prevalence rate obtained in this study suggests that 5 million workers in the UK have very high levels of occupational stress.

Cohort Studies↗
PubMed2000

Linkage analysis of chromosome 2q in osteoarthritis.

BACKGROUND: In independent linkage studies chromosome 2q11-q24 and chromosome 2q23-35 have previously been implicated as regions potentially harbouring susceptibility loci for osteoarthritis (OA). OBJECTIVE: To test chromosome 2q for linkage to idiopathic osteoarthritis. METHODS: Using a cohort of 481 OA families that each contained at least one affected sibling pair with severe end-stage disease (ascertained by hip or knee joint replacement surgery), we conducted a linkage analysis of chromosome 2q using 16 polymorphic microsatellite markers at an average spacing of one marker every 8.5 cM. RESULTS: Our results provide suggestive evidence for a locus at 2q31 with a maximum multipoint logarithm of the odds score (MLS) of 1.22 which increased to 2.19 in those families concordant for hip-only disease (n = 311). This suggestive linkage was greater in male-hip families (MLS = 1.57, n = 71) than in female-hip families (MLS = 0.71, n = 132). CONCLUSIONS: Chromosome 2q is likely to contain at least one susceptibility locus for OA.

Adult↗