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Biomedical subjects

D G Smith

Publications and source records attributed to D G Smith.

At least 19 recordsLinked to original sources
PubMed2003

Efficacy of danofloxacin 18% injectable solution in the treatment of Escherichia coli diarrhoea in young calves in Europe.

The efficacy of danofloxacin 18% against naturally occurring Escherichia coli diarrhoea was investigated in calves at seven European sites. Treatment commenced on day 0, with either a single subcutaneous injection of danofloxacin 18% (n=267) at 6 mg/kg repeated on day 2 if required, or reference product containing baquiloprim/sulphadimidine (n=37) or gentamicin (n=98) administered as recommended. E. coli was isolated from 90% to 100% of calves pre-treatment, and the prevalence of serotypes K99 and F41 was 8-46% and 46-92%, respectively. In both treatments, the majority of calves (93.2-93.9%) showed clinical improvement and completed the studies. There were significant reductions for both treatments, in severity of clinical signs on days 4 and 10 compared to day 0 (P<0.0001), and between days 4 and 10 (P<0.05), but no significant differences between treatments (P>0.05). Danofloxacin 18% was clinically safe, and as effective as the reference products in the treatment of E. coli diarrhoea in calves.

Animals↗
PubMed2003

Chronic fatigue syndrome in children: a cross sectional survey.

BACKGROUND: Chronic fatigue syndrome (CFS) in children is a controversial diagnosis with unclear aetiology, ill defined but likely increasing incidence, and debatable clinical management options. However these children experience real and considerable suffering. Appropriate research in this clinical population is sparse and usually occurs in tertiary referral units. METHODS: Cross sectional survey of 36 children attending a GP specialist interest clinic in southeast England. RESULTS: Patient sociodemographics and clinical morbidity were largely comparable to the literature from tertiary referral research centres. Some prognostic indicators for adults did not readily transfer to this younger age group, although several children had a positive family psychiatric history. Receiving treatment was associated with increased school attendance, but one third of subjects obtained no qualifications. Return to normal health or significant overall improvement was reported by 29/36 subjects. CONCLUSIONS: The outcomes in this setting are favourable and comparable to those seen in a controlled setting; this study supports the concept that the prognosis for CFS in children and adolescents is generally good. However, the impact of the illness is significant and this is perhaps most evident in terms of education. Current methods of reporting educational outcomes in the literature are varied and merit development of standardised tools.

Absenteeism↗
PubMed2002

CD23 shedding: requirements for substrate recognition and inhibition by dipeptide hydroxamic acids.

CD23 (low affinity IgE receptor, FcepsilonRII) is expressed as a Type II extracellular protein on a variety of cells such as B cells, monocytes and macrophages and is cleaved from the cell surface to generate several distinct fragments. The expression of CD23 on the cell surface as well as the generation of soluble fragments of CD23 has been shown to be involved in regulation of IgE synthesis. CD23 is released from the cell surface by a metalloprotease, analogous to the cleavage of other cell surface molecules such as TNF-alpha. This activity has been extensively studied with respect to biochemical characterization and ability to cleave specific mutants of CD23. Both local sequence and distal domains have been shown to affect cleavage of CD23. Selective dipeptide hydroxamic acid inhibitors of CD23 processing have been identified and demonstrated to very potently and selectively inhibit CD23 processing.

Binding Sites↗
PubMed2002

Pharmacokinetics of selamectin following intravenous, oral and topical administration in cats and dogs.

The pharmacokinetics of selamectin were evaluated in cats and dogs, following intravenous (0.05, 0.1 and 0.2 mg/kg), topical (24 mg/kg) and oral (24 mg/kg) administration. Following selamectin administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). After intravenous administration of selamectin to cats and dogs, the mean maximum plasma concentrations and area under the concentration-time curve (AUC) were linearly related to the dose, and mean systemic clearance (Clb) and steady-state volume of distribution (Vd(ss)) were independent of dose. Plasma concentrations after intravenous administration declined polyexponentially in cats and biphasically in dogs, with mean terminal phase half-lives (t(1/2)) of approximately 69 h in cats and 14 h in dogs. In cats, overall Clb was 0.470 +/- 0.039 mL/min/kg (+/-SD) and overall Vd(ss) was 2.19 +/- 0.05 L/kg, compared with values of 1.18 +/- 0.31 mL/min/kg and 1.24 +/- 0.26 L/kg, respectively, in dogs. After topical administration, the mean C(max) in cats was 5513 +/- 2173 ng/mL reached at a time (T(max)) of 15 +/- 12 h postadministration; in dogs, C(max) was 86.5 +/- 34.0 ng/mL at T(max) of 72 +/- 48 h. Bioavailability was 74% in cats and 4.4% in dogs. Following oral administration to cats, mean C(max) was 11,929 +/- 5922 ng/mL at T(max) of 7 +/- 6 h and bioavailability was 109%. In dogs, mean C(max) was 7630 +/- 3140 ng/mL at T(max) of 8 +/- 5 h and bioavailability was 62%. There were no selamectin-related adverse effects and no sex differences in pharmacokinetic parameters. Linearity was established in cats and dogs for plasma concentrations up to 874 and 636 ng/mL, respectively. Pharmacokinetic evaluations for selamectin following intravenous administration indicated a slower elimination from the central compartment in cats than in dogs. This was reflected in slower clearance and longer t(1/2) in cats, probably as a result of species-related differences in metabolism and excretion. Inter-species differences in pharmacokinetic profiles were also observed following topical administration where differences in transdermal flux rates may have contributed to the overall differences in systemic bioavailability.

Administration, Oral↗
PubMed2001

Lawsonia intracellularis: getting inside the pathogenesis of proliferative enteropathy.

Although proliferative enteropathy (PE) has been recognised for several decades, Lawsonia intracellularis, the aetiological agent, was identified formally in only 1995. This organism is both highly fastidious and obligately intracellular bacterium, characteristics which have inevitably restricted investigations in all aspects of its biology. Despite these limitations, advances have been made in characterising and understanding L. intracellularis-host interaction both in vivo and in vitro. Based upon evidence provided by mainly pathological and histological investigations conducted to date, we review salient features of our current understanding of processes involved throughout the course of infection by this unique pathogen.

Animals↗
PubMed2001

Use of DNase to eliminate contamination in ancient DNA analysis.

Using polymerase chain reaction (PCR) amplification, it is possible to analyze DNA from limited source template. This method has proved especially valuable in studies of ancient DNA and in forensic investigations. However, PCR reactions containing minimal or damaged source template are prone to contamination by DNA from a number of other sources. While standard protocols to prevent and/or detect contamination do exist, methods of eliminating contamination are needed to ensure the validity of results obtained. We present a method to eliminate sources of contamination in reagents and labware through the use of a DNase prior to PCR amplification without damaging even the minimal amounts of template present in ancient DNA samples. This method, suggested previously for forensics applications, appears to be effective in eliminating contamination without interfering with the amplification of ancient template.

Deoxyribonucleases↗
PubMed2001

Ancient mitochondrial DNA evidence for prehistoric population movement: the Numic expansion.

The mitochondrial DNA of modern Native Americans has been shown to fall into one of at least five haplogroups (A, B, C, D, or X) whose frequencies differ among tribal groups. The frequencies of these five haplogroups in a collection of ancient individuals from Western Nevada dating to between approximately 350-9,200 years BP were determined. These data were used to test the hypothesis, supported by archaeological and linguistic data, that the current inhabitants of the Great Basin, the Numic speakers, are recent immigrants into the area who replaced the previous non-Numic inhabitants. The frequency distributions of haplogroups in the ancient and modern Native Americans differed significantly, suggesting that there is a genetic discontinuity between the ancient inhabitants and the modern Numic speakers, providing further support for the Recent Numic Expansion hypothesis. The distribution of mitochondrial haplogroups of the ancient inhabitants of the Great Basin is most similar to those of some of the modern Native American inhabitants of California.

Anthropology, Physical↗
PubMed2001

Major histocompatibility complex class II polymorphisms in Macaca mulatta: factors influencing comprehensive genotyping of Macaca mulatta (Mamu)-DQA1 alleles by PCR-RFLP in archival samples.

In the last 5 years, HLA class II genotyping methods have been adapted for genotyping of class II loci in rhesus macaques. Since previously published typing protocols were used on samples that were collected and stored under ideal conditions, it was of interest to determine if these methods were adequate for genotyping a large collection of archival samples from which DNA had been isolated and stored under various conditions. Established macaque DQA1 typing protocols were modified to optimize the typing procedure and enhance the ability to successfully genotype DNA from samples that were of poor quality and/or quantity. Long-term storage of whole-blood buffy coats or stored DNA extracted from whole-blood buffy coats did not affect typing success; however, amplification and typing of DNA extracted from archival samples of plasma were difficult and resulted in a low success rate. This suggests that amplification and DQA1-genotyping of archival samples is possible with a modified protocol, but is influenced by the age and source of the sample, and to a lesser extent, the method used to extract DNA from sample substrates.

Animals↗
PubMed2001

Phylogenetic relationships among the macaques: evidence from the nuclear locus NRAMP1.

The macaques, genus Macaca, represent one of the most successful radiations within the Order Primates, with a geographical distribution that ranks second in size only to that of humans among extant primates. Although the number of macaque species recognized depends on the classification scheme used, most authors currently follow the classifications of either Fooden or Delson, both of whom recognize 19 extant macaque species. These two classifications differ in their placement of macaque species into more inclusive taxa (i.e., species groups). While researchers have attempted to use mitochondrial DNA (mtDNA) to resolve these phylogenetic relationships, different studies have generated conflicting conclusions. Consequently, we screened nuclear DNA sequences of a large number of macaques to determine if such data provide greater insight into the phylogenetic relationships among macaques. The data generated from the comparison of two (noncoding) introns within the natural resistance-associated macrophage protein 1 (NRAMP1) gene generally agree with the classification scheme of Delson. However, the data also support several novel observations. Specifically, the NRAMP1 data demonstrate that M. silenus and M. nemestrina lack nuclear genetic variation, while M. assamensis and M. radiata exhibit the greatest amount of genetic variation. In addition, these data suggest that M. fascicularis may not be as "primitive" (with respect to other members of the fascicularis group) as the mtDNA based data suggest.

Animals↗
PubMed2001

Plains cottonwood's last stand: can it survive invasion of Russian olive onto the Milk River, Montana floodplain?

Russian olive (Elaeagnus angustifolia L.) was introduced in 1950 onto one site on the Milk River floodplain, northern Montana, 10 km downstream from the Canada/United States border. To analyze dispersal of Russian olive from the point source between 1950 and 1999, we compared distribution, numbers, size structure, and mortality of Russian olive and plains cottonwood (Populus deltoides Marsh:) on an unregulated reach of the Milk River floodplain in southeastern Alberta and north-central Montana. Within 50 years, Russian olive in this reach has moved upriver into Alberta and downriver to the Fresno Reservoir. It is now present on 69 of the 74 meander lobes sampled, comprising 34%, 62%, and 61% of all Russian olive and plains cottonwood seedlings, saplings, and trees, respectively. On some meander lobes, Russian olive has colonized similar elevations on the floodplain as plains cottonwood and is oriented in rows paralleling the river channel, suggesting that recruitment may be related to river processes. Breakup ice had killed 400 Russian olive saplings and trees and damaged >1000 others on 30 of the meander lobes in 1996. Nevertheless, Russian olive now outnumbers cottonwood on many sites on the Milk River floodplain because its seeds can be dispersed by wildlife (particularly birds) and probably by flood water and ice rafts; seeds are viable for up to 3 years and germination can take place on bare and well-vegetated soils; and saplings and trees are less palatable to livestock and beaver than plains cottonwood. Without control, Russian olive could be locally dominant on the Milk River floodplain in all age classes within 10 years and replace plains cottonwood within this century.

Animals↗
PubMed2001

Corneal bee sting with retained stinger.

Bee stings of the cornea are rarely reported, but have the potential for causing serious ophthalmologic injuries. We present a case of corneal bee sting with retained stinger apparatus and associated iritis and discuss the pathologic mechanisms of injury, evaluation, and treatment of these uncommon presentations.

Adult↗
PubMed2001

The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation.

BACKGROUND: Glycogen synthase kinase-3 (GSK-3) sequentially phosphorylates four serine residues on glycogen synthase (GS), in the sequence SxxxSxxxSxxx-SxxxS(p), by recognizing and phosphorylating the first serine in the sequence motif SxxxS(P) (where S(p) represents a phosphoserine). FRATtide (a peptide derived from a GSK-3 binding protein) binds to GSK-3 and blocks GSK-3 from interacting with Axin. This inhibits the Axin-dependent phosphorylation of beta-catenin by GSK-3. RESULTS: Structures of uncomplexed Tyr216 phosphorylated GSK-3beta and of its complex with a peptide and a sulfate ion both show the activation loop adopting a conformation similar to that in the phosphorylated and active forms of the related kinases CDK2 and ERK2. The sulfate ion, adjacent to Val214 on the activation loop, represents the binding site for the phosphoserine residue on 'primed' substrates. The peptide FRATtide forms a helix-turn-helix motif in binding to the C-terminal lobe of the kinase domain; the FRATtide binding site is close to, but does not obstruct, the substrate binding channel of GSK-3. FRATtide (and FRAT1) does not inhibit the activity of GSK-3 toward GS. CONCLUSIONS: The Axin binding site on GSK-3 presumably overlaps with that for FRATtide; its proximity to the active site explains how Axin may act as a scaffold protein promoting beta-catenin phosphorylation. Tyrosine 216 phosphorylation can induce an active conformation in the activation loop. Pre-phosphorylated substrate peptides can be modeled into the active site of the enzyme, with the P1 residue occupying a pocket partially formed by phosphotyrosine 216 and the P4 phosphoserine occupying the 'primed' binding site.

Amino Acid Motifs↗
PubMed2001

Amputation. Preoperative assessment and lower extremity surgical techniques.

Amputation surgery is an important part of the treatment for severe limb disorders. The decision-making process must be done thoughtfully, remembering that blood flow is not the only issue. Many factors enter into the decision to perform a partial foot amputation or to perform a more proximal level amputation. Adherence to good surgical principles, proven techniques, and gentle soft tissue handling can make the difference between a successful and durable amputation or continued complications and frustrations.

Amputation, Surgical↗
PubMed2001

Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection.

There is good evidence that the kynurenine pathway (KP) and one of its products, quinolinic acid (QUIN), play a role in the pathogenesis of neurological diseases, in particular AIDS dementia complex. Although QUIN has been shown to be produced in neurotoxic concentrations by macrophages and microglia, the role of astrocytes in QUIN production is controversial. Using cytokine-stimulated cultures of human astrocytes, we assayed key enzymes and products of the KP. We found that human astrocytes lack kynurenine hydroxylase so that large amounts of kynurenine and the QUIN antagonist kynurenic acid were produced. However, the amounts of QUIN that were synthesized were subsequently completely degraded. We then showed that kynurenine in concentrations comparable with those produced by astrocytes led to significant production of QUIN by macrophages. These results suggest that astrocytes alone are neuroprotective by minimizing QUIN production and maximizing synthesis of kynurenic acid. However, it is likely that, in the presence of macrophages and/or microglia, astrocytes become indirectly neurotoxic by the production of large concentrations of kynurenine that can be secondarily metabolized by neighbouring or infiltrating monocytic cells to form the neurotoxin QUIN.

AIDS Dementia Complex↗
PubMed2001

Emergency physician practice and steroid use in the management of acute exacerbations of asthma.

This study seeks to determine patterns of emergency physician (EP) practice regarding steroid use in the management of acute asthma attacks in the emergency department (ED), and to compare practices of academic and private practice EPs. Two hundred eight questionnaires were mailed to academic and private practice EPs. The survey requested information regarding the preferred initial route (oral or intravenous) for steroid administration; the initial dose of steroid; the preferred steroid regimen for outpatient management; and whether or not inhaled steroids were routinely prescribed at the time of discharge. The overall response rate was 74%; 91% for the academic EPs and 56% for private practice EPs. Sixty-five percent (99/143) of all EPs used the intravenous route for their initial dose of steroids. A significantly greater percentage of private practice EPs (45/58 or 78%) used intravenous steroids compared with academic EPs (54/95 or 57%; P = .009). A total of 41% (63/153) of EPs used a tapering steroid regime for outpatient therapy; a significantly greater percentage (34/58 or 59%; P = .0006) of private practice EPs used a tapering regimen of steroids compared with academic EPs (29/95 or 31%). A total of 32%(31) academic and 34% (20) private practice EPs prescribed inhaled steroids as part of their routine discharge instructions. Emergency physician practice patterns regarding initial steroid route of administration and dose, and outpatient-dosing regimens are variable. Only a minority of EPs prescribe steroid metered dose inhalers as part of their outpatient management of asthma.

Acute Disease↗
PubMed2001

Back pain as a secondary disability in persons with lower limb amputations.

OBJECTIVE: To evaluate the frequency, duration, intensity, and interference of back pain in a sample of persons with lower limb amputations. DESIGN: Retrospective, cross-sectional survey. SETTING: Community-based survey from clinical databases. PARTICIPANTS: Participants who were 6 or more months post lower limb amputation (n = 255). INTERVENTION: An amputation pain survey that included several standardized pain measures. MAIN OUTCOME MEASURES: Frequency, duration, intensity, and interference of back pain. RESULTS: Of the participants who completed the survey (return rate, 56%), 52% reported experiencing persistent, bothersome back pain. Of these, 43% reported average back pain intensity in the mild range (1-4 on 0-10 rating scale) and 25% reported pain of moderate intensity (5-6 on 0-10 scale). Most respondents with back pain rated the interference of their pain on function as none to minimal. However, nearly 25% of those with back pain described it as frequent, of severe intensity (>or=7 on 0-10 scale), and as severely interfering with daily activities including social, recreational, family, and work activities. CONCLUSIONS: Back pain may be surprisingly common in persons with lower limb amputations, and, for some who experience it, may greatly interfere with function.

Activities of Daily Living↗