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Biomedical subjects

R A Smith

Publications and source records attributed to R A Smith.

At least 127 records · Page 7Linked to original sources
PubMed1998

A microbore high performance liquid chromatography/electrospray ionization mass spectrometry method for the determination of the phytoestrogens genistein and daidzein in comminuted baby foods and soya flour.

A microbore high performance liquid chromatographic/electrospray/mass spectrometric (HPLC/ESI-MS) method has been developed for the determination of the phytoestrogens daidzein and genistein in soya flours and baby foods. The samples were hydrolysed and extracted with acetonitrile-water prior to analysis. LC was performed on a microbore Primesphere 5C8 column using a water/acetonitrile/acetic acid mobile phase at a flow rate of 60 microliters/min. Atmospheric pressure ionization in the form of pneumatically assisted electrospray mass spectrometry (ESI-MS) was used as the method of detection. The limit of detection was 0.2 mg/ kg for daidzein and 0.7 mg/kg for genistein in the flour and food samples. The method proved both robust and reliable when operated over a long time period (10 days, 463 injections) generating precision data with a coefficient of variation of 4-15%.

Calibration↗
PubMed1998

Environmental persistence of Bacillus thuringiensis spores following aerial application.

Soil and leaf populations of Bacillus thuringiensis (Bt) were monitored following aerial application of commercial Bt formulations at the rate of 72 billion international units per acre per year during a 5-year period. Data from soil sample spore counts suggested that Bt spores persisted in Wasatch forest soils for up to 2 years but they did not proliferate. Bt isolates were recovered from leaf samples 12 months post application from sprayed, previously sprayed and from nonsprayed areas. The frequency and diversity of Bt isolates recovered from leaves was independent of sample area spray history. In accordance with U.S. Forest Service criteria, aerial application of Bt during a 5-year period resulted in the eradication of gypsy moth (Lymantria dispar, L) from the Wasatch Front region of the Wasatch Mountain Range, Utah.

Bacillus thuringiensis↗
PubMed1998

Urinary physiologic and chemical metabolic effects on the urothelial cytotoxicity and potential DNA adducts of o-phenylphenol in male rats.

ortho-Phenylphenol (OPP), a fungicide and antibacterial agent with food residues, is carcinogenic to rat bladder. The present studies provide information on changes in urinary composition and urinary metabolites, urothelial cytotoxicity and regenerative hyperplasia, and DNA adducts in male F344 rats fed OPP. An initial experiment evaluated dietary doses of 0, 1,000, 4,000, and 12,500 ppm OPP fed for 13 weeks. There was no evidence of urinary calculi, microcrystalluria, or calcium phosphate-containing precipitate, but urothelial cytotoxicity and hyperplasia occurred at the highest dose only. In a second experiment, rats were fed dietary OPP levels of 0, 800, 4,000, 8,000, and 12,500 ppm. Urinary pH was > 7 in all groups. Urinary volume was increased at the 2 highest doses with consequent decreases in osmolality, creatinine, and other solutes. Total urinary OPP metabolite excretions were increased, mostly excreted as conjugates of OPP and of phenylhydroquinone. Free OPP or free metabolites accounted for less than 2% excreted in the urine without a dose response. Urothelial toxicity and hyperplasia occurred only at doses of 8,000 and 12,500 ppm. OPP-DNA adducts were not detected in the urothelium at any dose. In summary, OPP produces cytotoxicity and proliferation of the urothelium at dietary doses > or = 8,000 ppm without formation of urinary solids. The paucity of unconjugated metabolites and the lack of OPP-DNA adducts suggests that OPP is acting as a bladder carcinogen in male rats by inducing cytotoxicity and hyperplasia without it or its metabolites directly binding to DNA.

Administration, Oral↗
PubMed1998

Measurement of borate in occupational environments.

The hydration stability for inhalable borate particles has been characterized as a function of temperature and relative humidity when collected by a field personnel monitor. The rate of hydration was measured for boric acid (B[OH]3); Neobor borax 5 mol (Na2O x 2B2O3 x 5H2O); borax 10 mol (Na2O x 2B2O3 x 10H2O); anhydrous boric acid (B2O3); and anhydrous borax (Na2O x 2B2O3). The particle size is large in bulk commercial products, such that they can be handled and stored without problems. However, inhalable dust particles, in the range of 20 microm (MMD), undergo hydration/dehydration rapidly owing to their high surface-to-volume ratio. The hydration state of a collected air sample was found to be strongly dependent on the conditions of relative humidity and temperature during its collection. As a consequence, the actual chemical species of dust being inspired cannot be identified accurately. Inhalable particles of borax 10 mol placed in a field personal monitoring cartridge and exposed to dry air at 2.0 L/min at 70 degrees F for 7 h undergo rapid dehydration, producing a sodium borate residue having significantly less than four waters of hydration. Likewise, inhalable particles of anhydrous boric acid and anhydrous borax were found to hydrate under normal atmospheric conditions. Borax 5 mol and boric acid were found to be stable to dehydration. In most cases, the specific borate species or borate compounds collected in a field monitor cannot be accurately characterized other than by their boron (B) content.

Borates↗
PubMed1998

Protection against kainate-induced excitotoxicity by adenosine A2A receptor agonists and antagonists.

The neuroprotective role of adenosine receptor agonists in various models of ischaemia and neuronal excitotoxicity has been attributed to adenosine A1 receptor activation. In this study we examine the role of the A2A receptor in the kainate model of excitotoxicity. Kainate (10 mg/kg) was administered systemically 10 min after the intraperitoneal injection of adenosine analogues. The A2A agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS21680) protected the hippocampus at concentrations of 0.1 and 0.01 mg/kg, but not at 2 microg/kg. The addition of the centrally acting adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine partially reduced protection only in the CA3a region, suggesting that only a small proportion of the protection was attributable to the A1 receptor. A less potent A2A agonist, N6-[2-(3,5-dimethyoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (1 mg/kg), provided only partial protection against kainate. 4-(2-[7-Amino-2-[2-furyl][1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl -amino]ethyl)phenol, a selective A2A antagonist, also showed protection against kainate-induced neuronal death, when administered alone or in combination with CGS21680. These results show that adenosine A2A receptor activation is protective against excitotoxicity. The protection is largely independent of A, receptor activation or blockade.

Adenosine↗
PubMed1998

Feedlot health and management.

Health programs based solely on vaccination and treatment regimens are often short-lived and unrewarding. The basis of any successful ongoing health program is a working health management system. The key to the success of the system is a functioning record system that generates information meaningful to management. The basic information generated should include morbidity and mortality data categorized by cause, the number of repeat treatments, and the number of chronic animals or railers. Goals should be set for each major category so that a database can be established for a feedlot operation to assess problems and progress. The most common reason for expectations not being achieved is factors that are largely beyond the control of the feed yard. Although attempts to address these factors should be periodically reviewed, attention to the health program and potential modifications are among the factors that we can control and modify as appropriate. BRD is the most important economic disease in the feedlot. Prearrival management is extremely important in assessing the risk category of incoming calves and in applying a preventive health strategy. Good husbandry, proper nutrition, proper pen maintenance, and selective immunization help to ensure that the cattle adapt quickly to the feed yard environment. Careful observation, timely effective therapy, and excellent hospital management increase the opportunity to produce cost-competitive, safe, and wholesome beef in a humane fashion with limited effects of the environment.

Animal Husbandry↗
PubMed1998

The effects of age and gender on the pharmacokinetics of irbesartan.

AIMS: Single dose pharmacokinetics and safety of irbesartan, an angiotensin II receptor antagonist, were evaluated in healthy young and elderly male and female subjects. METHODS: Irbesartan was administered as two 25 mg capsules after a 10 h fast to 12 young men, 12 young women, 12 elderly men and 12 elderly women. Serial blood and urine sample were collected up to 96 h after the dose. Plasma and urine samples were analysed for irbesartan by h.p.l.c./fluorescence methods. RESULTS: No statistically significant gender effects were observed in peak plasma concentration (Cmax), area under the curve (AUC), and terminal elimination half-life (t1/2) of irbesartan. The geometric mean AUC and Cmax increased by about 43% and 49%, respectively, in the elderly subjects. Also the time to peak was significantly shorter in the elderly subjects compared with that observed in the young subjects. Renal clearance ofirbesartan was significantly reduced in the elderly females but this reduction is not likely to be of any clinical relevance since less than 3% of the administered dose of irbesartan is excreted unchanged in the urine. CONCLUSIONS: Although there was an effect of age on the pharmacokinetics of irbesartan, based on the safety and efficacy profile, no adjustment in irbesartan dosage is necessary with respect to age or gender.

Adolescent↗
PubMed1998

Pharmacokinetics and pharmacodynamics of avitriptan in patients with migraine after oral dosing.

Avitriptan (BMS-180048) is a 5-HT1-like receptor agonist for the treatment of migraine. This double-blind, placebo-controlled, randomized, parallel-group study evaluated the pharmacokinetics, safety, and preliminary efficacy of avitriptan in patients with migraine during migrainous and pain-free states. Patients met the IHS criteria for migraine with or without aura and suffered one to six migraines per month for at least 1 year. Patients in a clinic experiencing a migraine headache received avitriptan 75 mg, 150 mg, or 200 mg or matching placebo capsules. Blood samples were obtained before and 0.25, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, and 6 hours after dosing. Headache intensity was rated before and up to 6 hours after dosing. Seven to 30 days after the inclinic treatment, patients returned in a pain-free state for the same study medication. All pharmacokinetic and safety measures were repeated. Forty-eight patients (9 men and 39 women) participated. Peak plasma concentrations of avitriptan were achieved 1 to 2 hours following dosing in migraine and pain-free states for all doses. The pharmacokinetics of avitriptan were proportional to dose during a migraine attack over the 75- to 200-mg dose range. The 150- and 200-mg doses of avitriptan demonstrated a greater decrease in headache intensity scores at 2 hours postdose. The most common adverse event was paresthesia. Thus, avitriptan was rapidly absorbed, well tolerated, and demonstrated preliminary efficacy in this population.

Administration, Oral↗
PubMed1998

Intermittent CPAP: a new mode of ventilation during general anesthesia.

BACKGROUND: Airway pressure-release ventilation provides ventilation comparable to controlled mechanical ventilation (CMV), but with lower peak airway pressures and less dead-space ventilation. To obtain these advantages for patients administered general anesthesia, the authors (1) designed a mode similar to airway pressure-release ventilation, intermittent continuous positive airway pressure (CPAPI), and compared its efficiency with that of CMV; and (2) assessed the accuracy of end-tidal carbon dioxide tension (PETCO2) as a monitor of the partial pressure of carbon dioxide in arterial blood (PaCO2) during CPAPI compared with during CMV. METHODS: Twenty anesthetized, tracheally intubated patients received baseline CMV that produced a PETCO2 of approximately 35 mmHg and a pulse oximetry value > 90%. Patients were assigned to undergo alternating trials of CMV and CPAPI. During CPAPI, CPAP was applied to the airway, removed for 1 s, and reapplied at a rate equal to the ventilator rate during CMV. The difference between the carbon dioxide tension in arterial blood and end-tidal gas [P(a-ET)CO2] and the calculation of PaCO2/minute ventilation quantified the efficiency of ventilation. Data were summarized as mean +/- SD and compared using the Student's t-test. RESULTS: Peak airway pressure (13+/-2 vs. 23+/-5 cm H2O; P < 0.001) and minute ventilation (3.5+/-1 vs. 4.6+/-1.2 l/min; P < 0.0001) were lower during CPAPI than during CMV. The value for PaCO2/minute ventilation (11.1+/-2.9 vs. 7.9+/-2.6 mmHg x l(-1) x min(-1); P < 0.0001) was greater during CPAPI. P(a-ET)CO2 was always greater during CMV (6.3+/-1.6 vs. 1.7+/-0.9 mmHg; P < 0.0001) and was never > 3.5 mmHg during CPAPI. CONCLUSIONS: During CPAPI, less ventilation was necessary to produce a PaCO2 comparable to that during CMV. This represents a significant reduction in dead-space ventilation, improved efficiency of ventilation, and a lower value for P(a-ET)CO2. Compared with CMV, CPAPI also improves the accuracy of PETCO2 as a monitor of PaCO2.

Abdomen↗
PubMed1998

Reduction mammaplasty using the inferior pedicle technique.

A retrospective study of 350 reduction mammaplasties by the inferior pedicle technique performed over a 3-year period allows a critical evaluation of postoperative complications and patient satisfaction. The procedure can be done in a timely manner on an outpatient basis and is applicable to breasts of different shapes and sizes. The rate of postoperative complications (5%) was comparable with previous studies. Patient satisfaction was high (98%), with near-total relief of preoperative symptoms. Concern about the resultant scars was low (2%) when the incisions followed the natural contour of the breast.

Adult↗
PubMed1998

Synergism between Bacillus thuringiensis Spores and Toxins against Resistant and Susceptible Diamondback Moths (Plutella xylostella).

We studied the effects of combinations of Bacillus thuringiensis spores and toxins on the mortality of diamondback moth (Plutella xylostella) larvae in leaf residue bioassays. Spores of B. thuringiensis subsp. kurstaki increased the toxicity of crystals of B. thuringiensis subsp. kurstaki to both resistant and susceptible larvae. For B. thuringiensis subsp. kurstaki, resistance ratios were 1,200 for a spore-crystal mixture and 56,000 for crystals without spores. Treatment of a spore-crystal formulation of B. thuringiensis subsp. kurstaki with the antibiotic streptomycin to inhibit spore germination reduced toxicity to resistant larvae but not to susceptible larvae. In contrast, analogous experiments with B. thuringiensis subsp. aizawai revealed no significant effects of adding spores to crystals or of treating a spore-crystal formulation with streptomycin. Synergism occurred between Cry2A and B. thuringiensis subsp. kurstaki spores against susceptible larvae and between Cry1C and B. thuringiensis subsp. aizawai spores against resistant and susceptible larvae. The results show that B. thuringiensis toxins combined with spores can be toxic even though the toxins and spores have little or no independent toxicity. Results reported here and previously suggest that, for diamondback moth larvae, the extent of synergism between spores and toxins of B. thuringiensis depends on the strain of insect, the type of spore, the set of toxins, the presence of other materials such as formulation ingredients, and the concentrations of spores and toxins.

Journal Article↗
PubMed1998

A novel point mutation at position 156 of reverse transcriptase from feline immunodeficiency virus confers resistance to the combination of (-)-beta-2',3'-dideoxy-3'-thiacytidine and 3'-azido-3'-deoxythymidine.

Mutants of feline immunodeficiency virus (FIV) resistant to (-)-beta-2',3'-dideoxy-3'-thiacytidine (3TC) were selected by culturing virus in the presence of increasing stepwise concentrations of 3TC. Two plaque-purified variants were isolated from the original mutant population, and both of these mutants were resistant to 3TC. Surprisingly, these mutants were also phenotypically resistant to 3'-azido-3'-deoxythymidine (AZT) and to the combination of 3TC and AZT. Purified reverse transcriptase (RT) from one of these plaque-purified mutants was resistant to the 5'-triphosphates of 3TC and AZT. DNA sequence analysis of the RT-encoding region of the pol gene amplified from the plaque-purified mutants revealed a Pro-to-Ser mutation at position 156 of RT. A site-directed mutant of FIV engineered to contain this Pro-156-Ser mutation was resistant to 3TC, AZT, and the combination of 3TC and AZT, confirming the role of the Pro-156-Ser mutation in the resistance of FIV to these two nucleoside analogs. This represents the first report of a lentiviral mutant resistant to the combination of AZT and 3TC due to a single, unique point mutation.

Amino Acid Sequence↗
PubMed1998

In vitro techniques for the assessment of neurotoxicity.

Risk assessment is a process often divided into the following steps: a) hazard identification, b) dose-response assessment, c) exposure assessment, and d) risk characterization. Regulatory toxicity studies usually are aimed at providing data for the first two steps. Human case reports, environmental research, and in vitro studies may also be used to identify or to further characterize a toxic hazard. In this report the strengths and limitations of in vitro techniques are discussed in light of their usefulness to identify neurotoxic hazards, as well as for the subsequent dose-response assessment. Because of the complexity of the nervous system, multiple functions of individual cells, and our limited knowledge of biochemical processes involved in neurotoxicity, it is not known how well any in vitro system would recapitulate the in vivo system. Thus, it would be difficult to design an in vitro test battery to replace in vivo test systems. In vitro systems are well suited to the study of biological processes in a more isolated context and have been most successfully used to elucidate mechanisms of toxicity, identify target cells of neurotoxicity, and delineate the development and intricate cellular changes induced by neurotoxicants. Both biochemical and morphological end points can be used, but many of the end points used can be altered by pharmacological actions as well as toxicity. Therefore, for many of these end points it is difficult or impossible to set a criterion that allows one to differentiate between a pharmacological and a neurotoxic effect. For the process of risk assessment such a discrimination is central. Therefore, end points used to determine potential neurotoxicity of a compound have to be carefully selected and evaluated with respect to their potential to discriminate between an adverse neurotoxic effect and a pharmacologic effect. It is obvious that for in vitro neurotoxicity studies the primary end points that can be used are those affected through specific mechanisms of neurotoxicity. For example, in vitro systems may be useful for certain structurally defined compounds and mechanisms of toxicity, such as organophosphorus compounds and delayed neuropathy, for which target cells and the biochemical processes involved in the neurotoxicity are well known. For other compounds and the different types of neurotoxicity, a mechanism of toxicity needs to be identified first. Once identified, by either in vivo or in vitro methods, a system can be developed to detect and to evaluate predictive ability for the type of in vivo neurotoxicity produced. Therefore, in vitro tests have their greatest potential in providing information on basic mechanistic processes in order to refine specific experimental questions to be addressed in the whole animal.

Animals↗
PubMed1998

Impact of disease on feedlot performance: a review.

Morbidity and mortality of feedlot cattle have a variety of causes. Compared to respiratory disease, metabolic and digestive disorders generally are less prevalent and occur later in the feeding period. In addition to the obvious costs related to animal death and medication, subsequent performance of sick cattle often is depressed substantially. Closer coordination between veterinarians, nutritionists, and feedlot managers should help reduce the incidence of morbidity and mortality of feedlot cattle.

Animals↗
PubMed1998

The efficacy of hyaluronic acid foam as a middle ear packing agent in experimental tympanoplasty.

The efficacy of hyaluronic acid (HA) foam in the prevention of middle ear adhesions and other structural abnormalities in guinea pigs undergoing experimental tympanoplasty was investigated. Postoperative changes in the middle ear were evaluated by light microscopy after 6 weeks. The presence of adhesions, diminution of airspace, new bone formation, tympanic membrane (TM) formation, and mucosal inflammation was characterized by an objective grading system. Results were compared to absorbable gelatin sponge (AGS) and a control group (no middle ear packing). The control group showed the best average scores for all parameters tested except for adhesion formation. However, these results were statistically significant only when compared with those of the AGS group for airspace preservation, new bone formation, and TM formation. Although the HA foam group showed better average results than did the AGS group for all parameters tested, none were statistically significant. Although HA foam appears to be a promising middle ear packing agent, further experimental trials are warranted before any firm conclusions may be made.

Adjuvants, Immunologic↗
PubMed1997

Detection of DNA adducts by 32P postlabeling following chronic exposure of rats to snuff.

A surgically created canal was used as a reservoir for instillation of snuff into the lower lip of rats for 10 weeks. DNA was isolated and digested with micrococcal nuclease/spleen phosphodiesterase. Polar DNA adducts were detected in all tissues examined when digests were fractionated by high performance liquid chromatography (HPLC), 32P postlabeled, 3' dephosphorylated and analyzed by two-dimensional thin layer chromatography (TLC). DNA adducts derived from aromatic carcinogens were not detected when digests were 32P postlabeled and analyzed by four-dimensional thin layer chromatography. These results suggest that non-aromatic agents initiate carcinogenesis following exposure to snuff. The adduction to DNA in organs of the gastrointestinal tract and the kidneys indicates that snuff usage results in systemic exposure to carcinogens and may contribute to the incidence of neoplasms in organs outside the oral cavity.

Animals↗
PubMed1997

NMR analysis of main-chain conformational preferences in an unfolded fibronectin-binding protein.

A 130-residue fragment of the Staphylococcus aureus fibronectin-binding protein has been found to exist in a highly unfolded conformation at neutral pH. Measurement of experimental NMR 3JHNalpha coupling constants provides evidence for individual residues having distinct main-chain conformational preferences that are dependent both on the amino acid concerned and on neighbouring residues in the sequence. Analysis shows that these variations in the populations of individual residues can be explained in detail in terms of statistical distributions of conformational states derived from the protein data base. In particular, when the preceding residue has a beta-branched or aromatic side-chain, a significant increase occurs in the population of the less sterically restricted b region of phi,psi space. The results indicate that the local structure of the fibronectin binding protein in solution, under conditions where it displays full activity, approximates very closely to a statistical random coil structure. This may be an important feature in the biological role of this and other polypeptides involved in protein-protein interactions.

Adhesins, Bacterial↗