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Biomedical subjects

D R Smith

Publications and source records attributed to D R Smith.

At least 55 records · Page 3Linked to original sources

Blood carbon monoxide and hydrogen cyanide concentrations in the fatalities of fire and non-fire associated civil aviation accidents, 1991-1998.

Blood samples submitted to the Civil Aeromedical Institute (CAMI) from aviation accident fatalities are analyzed for carbon monoxide (CO), as carboxyhemoglobin (COHb), and hydrogen cyanide, as cyanide (CN(-)). These analyses are performed to establish possible exposure of victims to smoke from in-flight/post-crash fires or to CO from faulty exhaust/heating systems. The presence of both gases in blood would suggest that the victim was alive and inhaled smoke. If only COHb is elevated, the accident (or a death) could be the result of CO contamination of the interior. Information pertaining to blood levels of these gases in aviation fatalities, in relation to the associated accidents, is scattered or not available, particularly with regard to toxicity. Therefore, considering that COHb> or =10% and CN(-)> or =0.25 microg/ml are sufficient to produce some degree of toxicological effects, the necessary information was extracted from the CAMI database. Samples from 3857 fatalities of 2837 aviation accidents, occurring during 1991-1998, were received; 1012 accidents, encompassing 1571 (41%) fatalities, were fire associated, whereas 1820 accidents were non-fire related. The remaining five accidents were of unknown fire status. There were fewer fire related fatalities and associated accidents in the (COHb> or =10% and CN(-)> or =0.25 microg/ml) category than that in the (COHb<10% and CN(-)<0.25 microg/ml) category. No in-flight fire was documented in the former category, but in-flight fires were reported in 14 accidents (18 fatalities) in the latter category. No non-fire accident fatality was found wherein levels of both gases were determined to be at or above the stated levels. There were 15 non-fire accidents with 17 fatalities wherein only COHb (10-69%) was elevated. The present study suggests that aviation fire accidents/fatalities were fewer than aviation non-fire accidents/fatalities and confirms that aviation accidents related to in-flight fires and CO-contaminated interiors are rare.

Accidents, Aviation↗

Experimental verification of a negative index of refraction.

We present experimental scattering data at microwave frequencies on a structured metamaterial that exhibits a frequency band where the effective index of refraction (n) is negative. The material consists of a two-dimensional array of repeated unit cells of copper strips and split ring resonators on interlocking strips of standard circuit board material. By measuring the scattering angle of the transmitted beam through a prism fabricated from this material, we determine the effective n, appropriate to Snell's law. These experiments directly confirm the predictions of Maxwell's equations that n is given by the negative square root of epsilon.mu for the frequencies where both the permittivity (epsilon) and the permeability (mu) are negative. Configurations of geometrical optical designs are now possible that could not be realized by positive index materials.

Journal Article↗

Regulation of the catalytic activity of preexisting tyrosinase in black and Caucasian human melanocyte cell cultures.

The activity of tyrosinase, the rate-limiting enzyme for melanin synthesis, is higher in Black skin melanocytes than in melanocytes derived from Caucasian skin. This variation in enzyme activity is not due to differences in tyrosinase abundance or tyrosinase gene activity, but, rather, is due to differences in the catalytic activity of preexisting tyrosinase. In melanocytes, tyrosinase is localized to the membrane of melanosomes and in Caucasian melanocytes the melanosome-bound enzyme is largely inactive. Conversely, in melanosomes of Black melanocytes, tyrosinase has high catalytic activity. Treatment of Caucasian melanocytes with the lysosomotropic compound ammonium chloride or with the ionophores nigericin and monensin results in a rapid and pronounced increase in tyrosinase activity. This increase occurs without any change in tyrosinase abundance, indicating that these compounds are increasing the catalytic activity of preexisting enzyme. Inhibition of the vacuolar proton pump V-ATPase by treatment of Caucasian melanocytes with bafilomycin also increases tyrosinase activity. In contrast to the 10-fold increase in tyrosinase observed in Caucasian melanocytes, neither ammonium chloride, monensin, nigericin, nor bafilomycin is able to increase the already high level of tyrosinase activity present in melanosomes of melanocytes derived from Black skin. Finally, staining of Caucasian melanocytes with the fluorescent weak base acridine orange shows that melanosomes of Caucasian, but not Black, melanocytes are acidic organelles. These data support a model for racial pigmentation that is based on differences in melanosome pH in Black and Caucasian skin types. The models suggests that melanosomes of Caucasian melanocytes are acidic, while those of Black individuals are more neutral. Since tyrosinase is inactive in an acid environment, the enzyme is largely inactive in Caucasian melanosomes but fully active in Black melanosomes.

Acridine Orange↗

Phenyl benzenesulfonamides are novel and selective 5-HT6 antagonists: identification of N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (SB-357134).

Substituted N-phenyl-4-methoxy-3-piperazin-1-ylbenzenesulfonamides and conformationally restricted analogues have been identified as high affinity and selective 5-HT6 antagonists. Compounds from this series had a range of pharmacokinetic profiles in rat and in general there was a correlation between clearance and CNS penetration. Based on its overall biological profile 2 (SB-357134) was selected for further pre-clinical evaluation.

Animals↗

In vitro inhibition of Sphaeropsis sapinea by natural stilbenes.

The effects of pinosylvin, pinosylvin monomethyl ether, pinosylvin dimethyl ether, and resveratrol on the fungal shoot blight and canker pathogen of conifers Sphaeropsis sapinea were examined in vitro. Effects of compounds, isolates, and concentrations on both conidial germination and mycelial growth were significant (values of P < 0.001), indicating inhibitory activity of these compounds.

Ascomycota↗

Experimental intoxication by larvae of Perreyia flavipes Konow, 1899 (Hymenoptera: Pergidae) in pigs and some aspects on its biology.

Two pigs were dosed with 5 and 10g/kg bw of fresh Perreyia flavipes larvae collected at the municipality of Pelotas. Two other pigs were dosed with 0.87 and 1.7g/kg of dry P. flavipes (equivalent to 5 and 10g/kg bw of fresh larvae). Another pig was dosed with 0.17g/kg of dry larvae, daily, during 20d. Forty-eight hours after the ingestion, all pigs that ingested single doses showed clinical signs and marked rise in serum aspartate aminotransferase. Alanine aminotransferase and gamma glutamiltransferase were also slightly increased. The pig dosed with 10g/kg of fresh larvae died in 96h. The others recovered in 4-5days after ingestion. No clinical signs were observed in the pigs dosed during 20d with 0.17g/kg of dry larvae. The main lesion observed in the pig dosed whit 10g/kg of fresh larvae was a centrilobular liver necrosis. These results confirmed the toxicity of P. flavipes for swine, demonstrated that the larvae maintain the toxicity after being dried, and suggest no cumulative effect in the larval toxicity. The larvae collected in the field were conditioned in boxes containing swards of native grasses and covered with gauze to prevent the escape of adults on emergence. The larvae pupated from August 11 to September 25. Emergency of adults occurred from February 10 to March 4. Adult females and males live only for 18-36 and 24-48h, respectively. The eggs had an incubation period of 26-33d. The larval period extend from March 1 to August 24.

Animals↗

Measurement of potency and lipids in monensin fermentation broth by near-infrared spectroscopy.

A transmission near-infrared (NIR) spectroscopic method for quantification of potency and lipids in monensin fermentation broth was developed and validated. Two multiple linear regression calibration curves were established for a set of 100 fermentation samples, correlating the appropriate absorption bands in the NIR spectrum to the laboratory reference methods; high-performance liquid chromatography for potency, and chloroform extraction for lipids. During method development, potency was found to be well correlated to NIR absorbances specific for monensin. While acceptable, correlation of NIR absorbances characteristic of oil to the chloroform lipid method was weaker due to a greater amount of relative variation in the lipid measurements. Following establishment of the optimal calibration curves, the NIR method for potency and lipids was validated for selectivity, accuracy, precision, and robustness. In order to investigate long-term drift in the measurement system, samples were tested both by the NIR and the reference methods over a 7-month period. The differences between results from the two measurements were calculated and statistically analyzed.

Algorithms↗

Non-regularly shaped plasmon resonant nanoparticle as localized light source for near-field microscopy.

We study numerically two-dimensional nanoparticles with a non-regular shape and demonstrate that these particles can support many more plasmon resonances than a particle with a regular shape (e.g. an ellipse). The electric field distributions associated with these different resonances are investigated in detail in the context of near-field microscopy. Depending on the particle shape, extremely strong and localized near-fields, with intensity larger than 105 that of the illumination wave, can be generated. We also discuss the spectral dependence of these near-fields and show that different spatial distributions are observed, depending which plasmon resonance is excited in the particle.

Journal Article↗

Comparison of dissociation-enhanced lanthanide fluorescent immunoassays to enzyme-linked immunosorbent assays for detection of staphylococcal enterotoxin B, Yersinia pestis-specific F1 antigen, and Venezuelan equine encephalitis virus.

The dissociation-enhanced lanthanide fluorescent immunoassays (DELFIA) were developed for the detection of staphylococcal enterotoxin B, Yersinia pestis-specific F1 antigen, and Venezuelan equine encephalitis virus. These assays were compared to previously developed enzyme-linked immunosorbent assays (ELISAs) by determining the sensitivity or limit of detection (LOD), the dynamic range, and the reproducibility of each assay in a number of different sample matrices. The sensitivity and specificity of each assay were then determined by using a small panel of blinded spiked and nonspiked samples. All three DELFIAs demonstrated at least 1 log greater sensitivity than corresponding ELISAs utilizing the same reagents and showed an increase in dynamic range of at least 2 log(10) concentrations. This increased LOD resulted in higher sensitivity rates for the DELFIA. The specificity of all of the assays evaluated was 100%, and no sample matrix effects were observed in either format. However, the reproducibility of the DELFIA was poor due to randomly distributed wells exhibiting excessive background signal (hot wells), which occurred throughout the evaluation. As this technology matures, the reproducibility of these assays should improve, as will the ability to identify hot wells. Despite its sensitivity, the logistical burden associated with the DELFIA and the technical expertise required to complete assays and interpret the data limit the application of this technology to reference or large clinical laboratories.

Animals↗

Genome sequence and comparative analysis of the solvent-producing bacterium Clostridium acetobutylicum.

The genome sequence of the solvent-producing bacterium Clostridium acetobutylicum ATCC 824 has been determined by the shotgun approach. The genome consists of a 3.94-Mb chromosome and a 192-kb megaplasmid that contains the majority of genes responsible for solvent production. Comparison of C. acetobutylicum to Bacillus subtilis reveals significant local conservation of gene order, which has not been seen in comparisons of other genomes with similar, or, in some cases closer, phylogenetic proximity. This conservation allows the prediction of many previously undetected operons in both bacteria. However, the C. acetobutylicum genome also contains a significant number of predicted operons that are shared with distantly related bacteria and archaea but not with B. subtilis. Phylogenetic analysis is compatible with the dissemination of such operons by horizontal transfer. The enzymes of the solventogenesis pathway and of the cellulosome of C. acetobutylicum comprise a new set of metabolic capacities not previously represented in the collection of complete genomes. These enzymes show a complex pattern of evolutionary affinities, emphasizing the role of lateral gene exchange in the evolution of the unique metabolic profile of the bacterium. Many of the sporulation genes identified in B. subtilis are missing in C. acetobutylicum, which suggests major differences in the sporulation process. Thus, comparative analysis reveals both significant conservation of the genome organization and pronounced differences in many systems that reflect unique adaptive strategies of the two gram-positive bacteria.

Amino Acid Sequence↗

Oral succimer decreases the gastrointestinal absorption of lead in juvenile monkeys.

Although succimer (Chemet, meso-2,3-dimercaptosuccinic acid, DMSA) is considered to be a safe and effective chelating agent for the treatment of lead poisoning in humans, there is concern that it may increase the gastrointestinal (GI) absorption and retention of Pb from exposures suffered concurrent with treatment. This concern is justified because the availability of Pb-safe housing during outpatient treatment with oral succimer is limited. We used a juvenile nonhuman primate model of moderate childhood Pb intoxication and a sensitive double stable Pb isotope tracer methodology to determine whether oral succimer chelation affects the GI absorption and whole-body retention of Pb. Infant rhesus monkeys (n = 17) were exposed to Pb daily for 1 year postpartum to reach and maintain a target blood lead (BPb) level of 35-40 microg/dL. Animals were administered succimer (n = 9) or vehicle (n = 8) over two successive 19 day succimer treatment regimens beginning at 53 and 65 weeks of age. The present study was conducted over the second chelation regimen only. Animals received a single intravenous (iv) dose of stable (204)Pb tracer (5 microg, 24.5 nmol) followed by a single oral dose of stable (206)Pb tracer (72.6 microg, 352 nmol) immediately before chelation, in order to specifically evaluate GI Pb absorption and whole-body Pb retention with treatment. We collected complete urine and fecal samples over the first 5 days and whole blood over the first 8 days of treatment for analyses of stable Pb isotopes using magnetic sector inductively-coupled plasma mass spectrometry. Results indicate that succimer significantly reduced the GI absorption of Pb (vehicle, 64.9% +/- 5.5; succimer, 37.0% +/- 5.8; mean +/- SEM). Succimer also significantly increased the urinary excretion of endogenous Pb by approximately 4-fold over the vehicle treatment, while endogenous fecal Pb excretion was decreased by approximately 33%. Finally, although succimer reduced the whole-body retention of endogenous Pb by approximately 10% compared to vehicle, the majority (77%) of the administered internal dose of Pb tracer was retained in the body when assessed after 5 days of treatment. These data do not support the concern that succimer treatment increases GI Pb absorption.

Administration, Oral↗

An analysis of a discrete complex skill using Bernstein's stages of learning.

The purpose of this study was to provide quantitative data about changes in coordination after practicing a racquetball forehand drive serve. Novice women (N = 10) were videotaped before and after 10 min. of practicing a racquetball forehand drive serve on Day 1, and after 10-min. practice sessions on consecutive Days 2 through 5. The PEAK5 Motion Measurement System was used to evaluate the following dependent variables: (a) range of motion of the wrist, elbow, upper torso, and pelvis from backswing to ball contact: (b) racket head velocity at ball contact; and (c) coordination. Coordination was evaluated based on analysis of the angular velocity graphs of each performance to assess sequencing and timing of the segmental contributions. Shared positive contribution was assessed between adjacent 2-segment combinations: pelvis-torso and elbow-wrist. A repeated-measures analysis of variance indicated racket velocity, pelvic rotation, and upper torso rotation significantly increased over the 5 days of practice. Although participants increased their pelvic and torso ranges of motion and racket velocity, improvement in coordination was not documented.

Adult↗

Trauma-specific intensive care units can be cost effective and contribute to reduced hospital length of stay.

Our hypothesis was that clinical outcomes are improved and cost and hospital length of stay (LOS) reduced as a result of the opening of a closed trauma intensive care unit (ICU). We conducted a cross-sectional study in a university-affiliated Level I trauma center. Our study population comprised trauma patients admitted to the ICU between June 1, 1996 and July 1, 1998 for at least 24 hours and with an Injury Severity Score (ISS) >16 (excluding those with severe brain injury). The main outcome measures were changes in LOS and number of ventilator days, prevalence of complications, changes in patient charges, and hospital costs. Two hundred four patients were included [trauma ICU (TICU) 60, surgical ICU 144]. The two groups were not statistically different in age, ISS, mechanism of injury, infection rate, and mortality; however, the TICU patients had a lower number of ventilator hours (83.1 vs 100.0; P = 0.007), lower ICU LOS (9.4 vs 12.1 days; P = 0.06), and lower total hospital LOS (15.6 vs 22.3 days; P = 0.01). Although this was not of statistical significance TICU patients had lower hospital charges ($125,383 vs $152,994; P = 0.06) and lower cost per case ($42,306 vs $47,548; P = 0.35) for a net savings of $314,520 during the first 6 months of operation of the TICU. This study suggests that improved clinical outcomes and decreases in cost and LOS are directly related to the opening of a closed trauma ICU.

Adult↗

Nursing in Taiwan.

Although 10 years ago there was a crucial nursing shortage, Taiwan is currently experiencing an oversupply due to recent education reforms. Many new junior colleges have now been approved to take nursing courses. Taiwanese nurses are graduating at greater numbers than are leaving the profession, causing an ever increasing surplus.

Accreditation↗

Nursing in Japan.

Explore the source record for details and available documents.

Accreditation↗

Negative refractive index in left-handed materials.

The real part of the refractive index n(omega) of a nearly transparent and passive medium is usually taken to have only positive values. Through an analysis of a current source radiating into a 1D "left-handed" material (LHM)-where the permittivity and permeability are simultaneously less than zero-we determine the analytic structure of n(omega), demonstrating frequency regions where the sign of Re[n(omega)] must, in fact, be negative. The regime of negative index, made relevant by a recent demonstration of an effective LHM, leads to unusual electromagnetic wave propagation and merits further exploration.

Journal Article↗

Succimer and the reduction of tissue lead in juvenile monkeys.

The extent to which succimer (2,3-dimercaptosuccinic acid, DMSA) chelation reduces target organ lead (Pb) levels, including the skeleton, relative to the cessation of Pb exposure is a primary consideration in evaluating its efficacy for reducing toxicity in children. Here, we utilized a rhesus monkey model of childhood Pb exposure and a sensitive stable (204)Pb isotope tracer methodology to determine the efficacy of succimer for reducing Pb in blood, liver, and skeletal tissues from chronic (>/=1 year) versus short-term (3-4 days) Pb exposures. Specific attention was paid to the efficacy of succimer treatment compared to the cessation of Pb exposure. Infant rhesus monkeys (n = 48) were exposed to Pb daily for 1 year or >1 year postpartum to reach and maintain a target blood Pb level of 35-40 microg/dL. Two successive 19-day succimer treatment regimens were administered at 53 and 65 weeks of age (30 mg/kg/day x 5 days followed by 20 mg/kg/day x 14 days). Blood was collected over the course of treatment, and liver and bone biopsy samples were collected on days 0, 5, and 20, relative to the start of treatment (day 0). Complete 24-h urine collections were conducted over the course of treatment. Results of the first chelation indicate that a single regimen of succimer treatment led to significant reductions in blood and liver Pb levels, relative to the placebo group. However, the cessation of Pb exposure alone (i.e., placebo) also led to significant reductions in blood and liver compared to pretreatment levels. Neither succimer nor the cessation of Pb exposure had a significant impact on bone lead levels. Blood Pb levels in the succimer-treated group rebounded within 5 days after treatment ended, becoming comparable with levels in the placebo group from that point on. Results from the second chelation indicate that succimer treatment is essentially equally efficacious in reducing blood Pb at moderate (20 microg/dL) levels where exposures ended >3 months previously and more elevated (40-50 microg/dL) levels where exposures ended just prior to treatment, relative to the placebo treatment. Finally, similar overall outcomes were observed for tissue Pb from recent exposures (i.e., (204)Pb tracer levels), indicating little or no apparent difference in the chelation of Pb from recent (3-4 days) versus long-term exposures. These data demonstrate that succimer does not reduce skeletal Pb levels, and they show that the efficacy of succimer for reducing blood Pb levels does not persist beyond the completion of treatment due to posttreatment rebounds in blood Pb from endogenous sources. They also demonstrate the relative benefit of eliminating Pb exposures, which serves to underscore the importance of primary prevention of Pb exposure. The extent to which these data reflect the efficacy of succimer for reducing neurocognitive impairment is not yet known, although those data are forthcoming.

Animals↗