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Biomedical subjects

R Barrett

Publications and source records attributed to R Barrett.

At least 19 recordsLinked to original sources
PubMed2006

High-resolution study of x-ray resonant Raman scattering at the K edge of silicon.

We report on the first high-resolution measurements of the K x-ray resonant Raman scattering (RRS) in Si. The measured x-ray RRS spectra, interpreted using the Kramers-Heisenberg approach, revealed spectral features corresponding to electronic excitations to the conduction and valence bands in silicon. The total cross sections for the x-ray RRS at the 1s absorption edge and the 1s-3p excitation were derived. The Kramers-Heisenberg formalism was found to reproduce quite well the x-ray RRS spectra, which is of prime importance for applications of the total-reflection x-ray fluorescence technique.

Journal Article↗
PubMed2006

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Adolescent↗
PubMed2006

Age-related differences in inter-digit coupling during finger pinching.

The present study was designed to examine the finger-pinch force control, digit force sharing and digit coupling relations of 13 young and 14 older adults. Subjects performed four isometric tri-digit finger-pinch force production conditions reflecting all combinations of mean force level (20 and 40% MVC) and target shape (constant and sinusoidal). Older adults had significantly reduced force control, as indicated by their greater levels of absolute and relative force variability and targeting error than young adults. The age-related loss of relative force control was more pronounced at low (20% MVC) than high (40% MVC) forces, and to a lesser extent, in sinusoidal than constant force conditions. Older adults had significantly greater peak and proportional power below 1.5 Hz than young adults, with this especially pronounced in constant force conditions. Digit force sharing results indicated that the index finger's contribution to total force was increased and the middle finger's contribution reduced in older than young adults. The results of the cross-correlation analyses revealed that older subjects had a significantly reduced level of coupling between the middle finger and the target force, thumb force and EMG signals, with longer time lags in comparison to young adults. These differences in force sharing and middle finger force coupling were more pronounced in sinusoidal than constant force conditions. Overall, these results suggest that the older adults' reduced force control reflected age-related differences in the sharing and coupling of the finger forces. The results also highlighted that tasks of this nature display a degree of task-dependency, with these overall differences in digit force output and coupling not consistently observed across all force conditions.

Adult↗
PubMed2005

Joint international evaluation of Milking Shorthorn dairy cattle for production traits.

Pedigree information and test-day records for the first 3 parities of Milking Shorthorn dairy cattle from 5 countries were analyzed. After editing, the data included 1,018,528 test-day records from 68,653 cows. A multiple-lactation random regression test-day model with Legendre polynomials of order 4 and a Bayesian method were used to estimate variance components for both single and multiple-countries. Fixed effects included herd-test-day class and regressions on DIM within age at calving-parity-season of calving. Random effects included animal genetic, permanent environmental, and residual effects. Average daily heritabilities from single country analyses ranged from 0.33 to 0.47 for milk yield and from 0.37 to 0.45 for protein yield across lactations and countries. Common sires (66) and their daughters were identified for creating a connected data set for simultaneous (co)variance component estimation of milk yield across all 5 countries. Between-country genetic correlations were low, with values from 0.08 to 0.46 and standard deviations from 0.08 to 0.12. Estimated breeding values for milk were generated for each animal using the same test-day animal model. Correlations among country estimated breeding values were higher than genetic correlations. Top 100 bull lists were generated on the scale of each country, and genetic progress was assessed. Future evaluation with increased genetic ties among countries may facilitate international comparison of Milking Shorthorns.

Analysis of Variance↗
PubMed2004

Augmented visual feedback increases finger tremor during postural pointing.

Physiological tremor in the upper limb of eight adults was examined during the performance of a unilateral pointing task under conditions where the visual feedback, limb used and target size were altered. All subjects were required to aim a hand-held laser pointer at a circular target 5.5 m away with the goal of keeping the laser emission within the centre of the target. Visual feedback was defined as either normal vision (NV) of their limb tremor, where the laser was switched off, or augmented vision (AV) where the laser was switched on. Postural tremor from the segments of the upper limb, forearm muscle EMG activity, and target accuracy measures were recorded and analysed in the time and frequency domains. Accuracy-tremor relations were assessed using cross correlation and linear regression. Results revealed a high degree of similarity in the general pattern of the tremor output seen for each limb segment across conditions with only scalar (amplitude) changes being seen as a function of the different constraints imposed. For any single condition the tremor amplitude increased from proximal to distal segments. The frequency profile for the tremor in any segment displayed two prominent frequency peaks (at 2-4 Hz and 8-12 Hz). A third, higher frequency peak (18-22 Hz) was observed in the index fingers only. Across all conditions significant coupling relations were observed only between the hand-finger and forearm-upper arm segment pairs. Altering the visual feedback was shown to have the greatest effect on limb tremor with increased tremor and EMG activity and decreased coupling being seen under AV conditions. In trying to reduce tremor output when the augmented feedback was provided novice subjects instead increased muscle activity which resulted in increased tremor. Overall these results indicate that the physiological tremor output observed in neurologically normal subjects is not simply the product of intrinsic oscillations but is influenced by the nature of the task being performed.

Adult↗
PubMed2004

Design and application of a novel brain slice system that permits independent electrophysiological recordings from multiple slices.

We describe a novel brain slice system 'SliceMaster' that allows electrophysiological recordings from eight brain slices independently. The system consists of two autonomous units each supporting four modular brain slice chambers enabling high signal-to-noise ratio recordings, each chamber has one stimulation electrode, one recording electrode, a twin camera system and a solution application system. The positioning of both electrodes and cameras are controlled from a remote user console. The software both acquires and performs on-line analysis of the data. We have demonstrated utility of this system in obtaining recordings of spontaneous firing activity and evoked synaptic activity from mouse hippocampal slices, with reduced variability within and between experiments. Furthermore, we show recordings of population spikes from the perirhinal cortex, indicating applicability of this system for further brain regions. In addition, stable recordings could be maintained until recording was terminated after 3 h, permitting investigation of the induction and maintenance of synaptic plasticity. Recordings of spontaneous and synaptic activity, and effects of pharmacological and electrophysiological manipulation, were consistent with reports using conventional methods. However, the described system permits concurrent and independent recordings from eight brain slices, thus improving throughput, statistical design, and reducing animal use.

Action Potentials↗
PubMed2001

B7/CD28 costimulation is critical in susceptibility to Pseudomonas aeruginosa corneal infection: a comparative study using monoclonal antibody blockade and CD28-deficient mice.

Evidence suggests that Pseudomonas aeruginosa stromal keratitis and corneal perforation (susceptibility) is a CD4(+) T cell-regulated inflammatory response following experimental P. aeruginosa infection. This study examined the role of Langerhans cells (LC) and the B7/CD28 costimulatory pathway in P. aeruginosa-infected cornea and the contribution of costimulatory signaling by this pathway to disease pathology. After bacterial challenge, the number of LC infiltrating the central cornea was compared in susceptible C57BL/6 (B6) vs resistant (cornea heals) BALB/c mice. LC were more numerous at 1 and 6 days postinfection (p.i.), but were similar at 4 days p.i., in susceptible vs resistant mice. Mature, B7 positive-stained LC in the cornea and pseudomonas Ag-associated LC in draining cervical lymph nodes also were increased significantly p.i. in susceptible mice. To test the relevance of these data, B6 mice were treated systemically and subconjunctivally with neutralizing B7 (B7-1/B7-2) mAbs. Treatment decreased corneal disease severity and reduced significantly the number of B7-positive cells as well as the recruitment and activation of CD4(+) T cells in the cornea. IFN-gamma mRNA levels also were decreased significantly in the cornea and in draining cervical lymph nodes of mAb-treated mice. When CD28(-/-) animals were tested, they exhibited a less severe disease response (no corneal perforation) than wild-type B6 mice and had a significantly lower delayed-type hypersensitivity response to heat-killed pseudomonas Ag. These results support a critical role for B7/CD28 costimulation in susceptibility to P. aeruginosa ocular infection.

Animals↗
PubMed2001

Transdermal dopaminergic D(2) receptor agonist therapy in Parkinson's disease with N-0923 TDS: a double-blind, placebo-controlled study.

N-0923 is a non-ergot, dopaminergic D(2) agonist designed to be transdermally available. It has anti-parkinsonian effects when infused intravenously. An adhesive matrix patch was developed to deliver N-0923 transdermally (N-0923 TDS). In this phase II trial, we evaluated the effectiveness of various doses of N-0923 TDS at replacing levodopa. Eighty-five Parkinson's disease (PD) patients were randomized to placebo or one of four doses of N-0923 TDS for 21 days. Change in daily levodopa dose was the primary efficacy measure. Significantly greater reductions in levodopa dose were achieved as compared to placebo for the two highest doses of N-0923 TDS. Patients treated with 33.5 mg and 67 mg N-0923 TDS decreased levodopa use by 26% and 28%, vs. 7% for placebo. N-0923 TDS was safe and well tolerated.

Administration, Cutaneous↗
PubMed2001

Measurement of paralytic shellfish toxins in molluscan extracts: comparison of the microtitre plate saxiphilin and sodium channel radioreceptor assays with mouse bioassay, HPLC analysis and a commercially available cell culture assay.

This study compared five methods of measuring paralytic shellfish toxins (PSTs) including the long-used mouse lethality bioassay, a commercially available cell culture test (MIST Quantification kit), HPLC analysis, and two newly developed radioreceptor assays utilizing mammalian sodium channels and saxiphilin. Methods were challenged with toxic shellfish extracts prepared according to the AOAC official method. The best correlations between predicted toxicity values being 0.9 or better, were those between HPLC analysis when compared with both radioreceptor assays and the mouse lethality bioassay, as well as that between the saxiphilin and the sodium channel radioreceptor assays. In all cases, statistically significant correlations existed between the toxicity measurements of the same extracts. The ratios between some methods were not unitary as measured by the slopes of the regression lines used for correlation analyses. HPLC analysis predicted more toxicity than all of the bioassays. The saxiphilin assay underestimated toxicity relative to the mouse bioassay, the MIST kit determinations and the sodium channel assay. The sodium channel assay predicted there to be less toxicity than the mouse bioassay and the MIST kit. Of all of the techniques used, the MIST kit correlation with the mouse bioassay was nearest to one. Each method possesses differentt virtues and it may be that a multi-method approach would harness the benefits of each method for various aspects of a shellfish testing regime.

Amphibian Proteins↗
PubMed2001

Screening for abuse: barriers and opportunities.

Domestic abuse is the leading cause of injuries and death among women of childbearing age in the United States. The broad purpose of this research is to discover how pregnant women's psychological and behavioral responses to abuse affect birth outcomes. To select a diverse sample of women, we identified 8 prenatal care sites and completed the human subjects approval process with each. Rates of screening for abuse range from all but 12 women over a 2-1/2-year period at one site to no screening for abuse at another site. In this article, we will review pertinent literature and discuss the supports and barriers we observed when implementing an abuse screening program using the Abuse Assessment Screen, a well-tested and valid clinical instrument. Suggestions will be made for improving the screening rates at those sites where screening is absent or inconsistent.

Attitude of Health Personnel↗
PubMed2001

Assessment of outcomes at alternative medicine cancer clinics: a feasibility study.

OBJECTIVE: This pilot study tested the feasibility of performing outcomes and more advanced research regarding cancer patients at two complementary and alternative (CAM) clinics. The primary objectives were to determine the feasibility of (1) obtaining and collecting data from medical records, (2) determining 5-year survival, and (3) comparing 5-year survival to that of conventional treatment. In addition, in this paper we present the barriers and recommend strategies to facilitate high-quality research. SETTINGS/LOCATION: The Bio-Medical Center in Tijuana, Mexico, and the Livingston Foundation Medical Center in San Diego, California. SUBJECTS: New patients who were treated for cancer during 1992 at the Livingston Foundation Medical Center and during the first quarter of 1992 at the Bio-Medical Center. RESULTS: Charts were available for 89.6% of the 307 new patients treated at the Bio-Medical Center; 149 (54%) patients were treated for cancer and 65 (43.6%) cases were confirmed by pathology reports. In contrast, all records were available for 193 new patients treated for cancer at the Livingston Clinic; 152 (78.8%) cases had pathology confirmation. At both clinics, patients were equally divided by gender and were predominantly Caucasian, were married, and were U.S. residents. On average, patients were 51-54 years old and within 1 year of diagnosis for breast, colorectal, lung, or male genital cancer. Most patients (61.1%-63.7%) arrived with distant or regional disease after conventional surgery and/or chemotherapy/radiotherapy. Survival at 5 years was determined for 57.0% at the Bio-Medical Center (11.4% were alive and 45.6% were deceased) and 94.8% at Livingston (14.5% were alive and 80.3% were deceased). The limited number of cases by cancer site prevented comparison to conventional treatment. CONCLUSIONS: Historical, widespread use of clinics such as these with anecdotal reports of extraordinary survival merit prospective, systematic monitoring of patient outcomes. For data to be meaningful, however, disease status must be pathologically confirmed and patient follow-up improved.

Adolescent↗
PubMed2000

Increased severity of Pseudomonas aeruginosa corneal infection in strains of mice designated as Th1 versus Th2 responsive.

PURPOSE: Mice favoring Th1 (C57BL/6, C57BL/10, and B10.D2/nSn) versus Th2 (BALB/c, BALB/cBy, BALB.B, and BALB.K) response development were evaluated for their response to infection with Pseudomonas aeruginosa. This study addresses the question of whether Th1 versus Th2 response propensity affects the pathogenesis of bacterial keratitis in mice. METHODS: Ocular disease was determined by mean clinical score, slit lamp, plate counts, and histopathology, and antigen-specific cellular responses were assessed by immunostaining and measurement of delayed type hypersensitivity (DTH). RESULTS: Strains of mice favoring Th1 (B6, BL10, and B10.D2) versus Th2 (BALB/c, BALB/cBy, BALB.B, and BALB.K) responsiveness were infected with P. aeruginosa. Mice favoring Th1 response development exhibited a similar course of disease and the infected eyes of all mice perforated by 7 days postinfection (p.i.). Strains (BALB/c, BALB/cBy, BALB.B, and BALB.K) favoring Th2 response development exhibited a milder course of disease, and none of the infected corneas perforated at 7 days p.i. In a Th1-responsive strain (B10.D2), positive immunostaining for CD4+ and CD8+ T cells was observed in the cornea by 3 days p.i. and by 5 days p.i., respectively, some cells stained positively for IL2-R, indicating that the cells were activated. In contrast, in a Th2 responder strain (BALB/c), there was no detectable positive immunostaining in cornea for any of the T-cell markers tested and DTH was significantly elevated in B10.D2 versus BALB/c mice. CONCLUSIONS: These studies are the first to provide evidence that in P. aeruginosa ocular infection, mouse strains favoring development of a Th1-type response are susceptible (cornea perforates), whereas strains favoring Th2 response development are resistant (no corneal perforation).

Animals↗
PubMed1999

Evidence for TIMP-1 protection against P. aeruginosa-induced corneal ulceration and perforation.

PURPOSE: To determine the biological significance of individual endogenous tissue inhibitors of metalloproteinases (TIMPs) in protection against tissue destruction using a Pseudomonas aeruginosa-induced model of corneal ulceration. METHODS: Corneal TIMP-1, -2, and -3 mRNA levels were compared between young adult (resistant) and aged (susceptible) mice challenged with P. aeruginosa. Resistant mice that demonstrated greater amounts of an individual TIMP were treated with polyclonal antibody (pAb) to that TIMP. To determine whether TIMP neutralization exacerbated P. aeruginosa-induced corneal disease, TIMP pAb- and normal rabbit serum (NRS)- (control) treated mice were examined macroscopically and histopathologically after infection. Corneal neutrophil (PMN) myeloperoxidase (MPO) levels also were examined in these mice. RESULTS: Greater amounts of TIMP-1 mRNA only were found in corneas of resistant versus suscep tible mice after P. aeruginosa challenge. Systemic treatment of resistant mice with TIMP-1 pAb resulted in corneal perforation by 5 to 7 days after infection (PI). Histopathologic evaluation of corneal tissues from TIMP-1 pAb- versus NRS-treated mice confirmed that TIMP-1 pAb treatment resulted in extensive stromal dissolution. This treatment also was associated with loss of epithelium within the central cornea. Both the histopathology and PMN MPO enzyme assays also showed an increase in corneal PMN number following TIMP-1 pAb treatment. CONCLUSIONS: These studies provide evidence that, after P. aeruginosa infection, adequate endogenous expression of TIMP-1 in cornea protects against extensive corneal tissue destruction. The protective effects of TIMP-1 may be multifactorial. In addition to directly protecting extracellular matrix components from active matrix metalloproteinases, TIMP-1 may either directly or indirectly influence recruitment of PMNs into infected cornea. Finally, TIMP-1 also may affect wound healing and resurfacing of the corneal epithelium.

Animals↗
PubMed1998

Kinetics of triglyceride rich lipoproteins: chylomicrons and very low density lipoproteins.

Lipoprotein dynamics are complex during the postprandial state. A significant rise in chylomicron concentration is associated with increased competition for LPL with VLDL particles. This results in an increased concentration of large VLDL. The concentration of small VLDL is reduced as a result of diminished conversion of large to small VLDL. Such changes, induced in the postprandial state, complicate the application and development of models that describe lipoprotein particle kinetics. The development of models that integrate chylomicron and VLDL particle information, rather than surrogate markers, together with data including other variables will provide insight into the complexity of lipoprotein metabolism in the postprandial state.

Animals↗
PubMed1998

Repositioning a slumped person in a wheelchair. A biomechanical analysis of three transfer techniques.

The purpose of this study was to determine the effect of three lifting techniques (unassisted lift, vertically assisted lift, and horizontally assisted lift) and two patient masses (65 kg and 75 kg) on loads acting on the lifter's spine when repositioning a wheelchair bound patient to a more upright sitting position. A static biomechanical model was used in conjunction with ground reaction force and videographic data to estimate compression and shear forces at the lumbosacral (L5/S1) joint. Results indicated that: L5/S1 compression forces associated with both unassisted and assisted transfers were of sufficient magnitude to warrant mechanical assistance; the two person technique with the assistant pushing the legs toward the back of the chair was associated with the lowest spinal loads; and L5/S1 compression forces were significantly greater for the vertically assisted lift compared to the unassisted lift. If a manual transfer is to be performed, the horizontally assisted lift is recommended to minimize loads on the lumbar spine of the lifter.

Adult↗
PubMed1997

A familial combined hyperlipidemic kindred with impaired apolipoprotein B catabolism. Kinetics of apolipoprotein B during placebo and pravastatin therapy.

Familial combined hyperlipidemia (FCHL) is a heterogeneous disorder characterized by multiple lipoprotein phenotypes, a high risk for coronary heart disease, and predominance among the LDL fraction of smaller and denser particles. We report on an FCHL kindred (the M-kindred) in which decreased VLDL- and LDL-apoB elimination rates rather than enhanced production rates were the main kinetic abnormalities. Lipoprotein levels and metabolic parameters of all apoB-containing lipoproteins (including light and dense LDLs) were determined during placebo and pravastatin treatment periods. ApoB metabolism was studied by endogenous labeling with stable isotopes and a multicompartmental model. Five members of the M-kindred participated. The study was doubly blinded, randomized, and placebo controlled. Treatment periods of 6 weeks were separated by 2-week washout periods. All subjects had high apoB levels, 2 had a mixed lipemia, 1 had hypercholesterolemia, and 2 had hypertriglyceridemia. Familial dysbetalipoproteinemia, hypercholesterolemia, and defective apoB-100 were excluded by genetic, testing. Kinetic parameters were remarkably similar in the five study subjects during the placebo period, despite their diverse plasma lipid profiles. Compared with nine normolipidemic control subjects, low VLDL-apoB fractional catabolic rates (FCRs) (3.6 +/- .1 versus 9.3 +/- 2.9 pools per day) and low LDL-apoB FCRs (0.19 +/- 0.05 versus 0.41 +/- 0.13 pool per day) were observed in every case. The majority of the LDL particles were identified in the denser fraction (d = 1.036 to 1.063 g/mL). A clear precursor-product relationship was observed from VLDL to IDL to light LDL to dense LDL, ie, there was no "metabolic channeling." Light LDL had significantly higher FCR than dense LDL (0.82 +/- 0.21 versus 0.22 +/- 0.08 pool per day). VLDL-apoB production rates were normal (19.7 +/- 6.0 versus 21.6 +/- 6.1 mg/kg per day for control subjects). In contrast, in two subjects drawn from two other FCHL kindreds (the C- and K-kindreds), VLDL-apoB production rates were increased (35.6 and 32.1 mg/kg per day, respectively). In these two, more "typical" FCHL subjects, FCRs of LDL-apoB were near normal (0.351 and 0.311 pool per day, respectively). Pravastatin (20 mg/d) resulted in significantly lower plasma cholesterol (265 +/- 30 to 218 +/- 16 mg/dL, P < .01), LDL cholesterol (186 +/- 31 to 145 +/- 15 mg/dL, P < .03), and apoB levels (168 +/- 14 to 125 +/- 16 mg/dL, P < .01) in the five FCHL subjects of the M-kindred. No changes were observed in plasma HDL cholesterol, apoA-I, or lipoprotein(a). Pravastatin significantly increased the LDL-apoB FCR (from 0.19 +/- 0.05 to 0.34 +/- 0.04 pool per day). The FCRs of both LDL subclasses increased with treatment. No pravastatin-induced changes were seen in apoB production rates.

Adolescent↗
PubMed1997

The effect of ofloxacin on the human corneal endothelium.

PURPOSE: Possible toxic effects of ofloxacin on human corneal endothelia were assessed by using electron microscopy and in vitro specular perfusion. METHODS: Five pairs of corneas [with one cornea of each pair receiving balanced salt solution (Endosol; Allergan, Irvine, CA, U.S.A.) and the other receiving Endosol with 10 micrograms/ml of ofloxacin] underwent perfusion for 3 h with corneal pachymetry every 15 min followed by tissue fixation. A mean corneal swelling rate was calculated from a first-order regression line fit for each of the five experiments. The swelling rates between groups was compared by-using a paired t test. Scanning and transmission electron micrographs were examined for cellular architecture. Another group of five pairs of corneas was perfused the same way with the only difference being a test dose of 30 micrograms/ml. RESULTS: The mean swelling rate for corneas perfused with 10 micrograms/ml of ofloxacin of -3.5 microns/h was not significantly different from that of the Endosol-alone corneas at -3.0 microns/h (p = 0.71). The mean swelling rate for corneas perfused at 30 micrograms/ml of ofloxacin was -4.1 microns/h, not significantly different from Endosol-alone perfused corneas at -6.5 microns/h (p = 0.08). No consistent ultrastructural changes could be attributed to exposure to 10 or 30 micrograms/ml of ofloxacin. CONCLUSION: Human corneal endothelium can be exposed to ofloxacin at a dose of 30 micrograms/ml for a period of 3 h without adverse ultrastructural or physiologic side effects.

Anti-Infective Agents↗