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Biomedical subjects

D Bennett

Publications and source records attributed to D Bennett.

At least 37 records · Page 2Linked to original sources

Treatment of canine and feline diaphyseal radial and tibial fractures with low-stiffness external skeletal fixation.

The healing of 62 cases of radial and tibial fractures treated with low-stiffness Kirschner-Ehmer external skeletal fixation frames (frame types 1a, 1a plus intramedullary pin [1aIMP], 1b and 2b) was evaluated. The mean time to clinical union was 65 days. All cases treated with 1b, 2b or 1aIMP frames healed. Four of 25 cases treated with 1a frames failed to heal due to premature pin loosening; these failures were in heavier patients than 1a cases which healed (P=0.041). Complications occurred in 40 of 62 cases, and were more common in cases treated with type 2b frames. Pin loosening was the most frequent complication (35 cases) and most commonly involved the most proximal pin (P<0.001). In type 2b frames, full pins loosened more frequently than half pins (P<0.001). This study indicates that canine and feline fractures can heal readily when treated with these frames, suggesting that more rigid type 2a or type 3 frames are unnecessary in the majority of cases. Increased morbidity compared with the use of more rigid frames need not be expected, but 1a frames should be avoided in heavier patients.

Animals↗

Health and access issues among Australian adolescents: a rural-urban comparison.

INTRODUCTION: Previous research has reported rural-urban differences in health concerns and access issues. However, very little of this has concerned young people, and what has been published has been mainly from countries other than Australia and may not generalise to Australian youth. The study described in this paper is a subset of a larger study on health concerns and access to healthcare for younger people (12-17 years) living in New South Wales (NSW), Australia. This paper reports findings on rural-urban similarities and differences. The specific study objective was to identify and describe rural-urban differences, especially those associated with structural disadvantage. METHOD: The reported findings form part of a larger state-wide cross-sectional study of access to healthcare among NSW adolescents. Adolescents were drawn from high schools in ten of the 17 Area Health Services in NSW. These Area Health Services were selected because they represent most aspects of rural-urban NSW with respect to population characteristics and health services. Eighty-one focus groups were conducted with adolescents (35 with boys and 46 with girls), of which 56 were conducted in urban, 22 in rural and 3 in regional areas. The focus groups were tape-recorded, transcribed and analysed using the computer software package NUD*IST 4. RESULTS: The analysis revealed certain health concerns that were common to both rural and urban adolescents: use of alcohol and illicit drugs, bullying, street safety, diet and body image, sexual health, stress and depression. However, certain concerns were mentioned more frequently in rural areas (eg depression), and two concerns were raised almost exclusively by rural youth (youth suicide and teenage pregnancy). There were also structural differences in service provision: adolescents in rural areas reported disadvantage in obtaining access to healthcare (limited number of providers and lengthy waiting times); having only a limited choice of providers (eg only one female doctor available), and cost (virtually no bulk billing--ie direct charge to Medicare with no patient co-payment). A lack of confidentiality as a barrier to seeking service access was raised by both rural and urban youth, but was a major concern in rural areas. No issues specific to urban areas were raised by urban youth. Male and female rural adolescents were more likely than urban adolescents to express concerns over limited educational, employment and recreational opportunities, which they believed contributed to their risk-taking behaviour. Gender differences were evident for mental health issues, with boys less able to talk with their peers or service providers about stress and depression than girls. These gender differences were evident among adolescents in both rural and urban areas, but the ethos of a self-reliant male who does not ask for help was more evident among rural boys. CONCLUSIONS: While Australian rural and urban youth shared many health concerns, rural-urban differences were striking in the almost exclusive reporting of youth suicide and teenage pregnancy by rural adolescents. The findings suggest that structural disadvantage in rural areas (limited educational, employment opportunities, and recreational facilities) impact adversely on health outcomes, particularly mental health outcomes, and contribute to risk-taking behaviour. Such disadvantages should be considered by health-service policy makers and providers to redress the imbalance. Gender differences were also evident and efforts to target the specific needs of Australian adolescent boys are warranted.

Journal Article↗

Preliminary study of joint disease in poultry by the analysis of synovial fluid.

Samples of synovial fluid and synovial membrane were obtained from the hock joints of several groups of broilers, including lame birds and two strains of broilers raised on different feeding regimens and given different drug treatments (carprofen or placebo). There were more significant differences between the groups on the basis of the analysis of the synovial fluid samples than the synovial membrane samples. Experimental birds fed ad libitum had the highest median red blood cell counts and median ghost cell counts of all of the groups, but there were no differences between the groups in the thickness of the synovial lining cell layer or the degree of cellular infiltrate in the synovial membrane. The synovial fluid from the broilers and lame birds fed ad libitum was more turbid, suggestive of intra-articular pathology, and the large numbers of heterophils in samples from the lame birds indicated an inflammatory arthropathy. The birds fed ad libitum which were treated with carprofen had more cells in the synovial fluid than the birds given the placebo. A large number of the samples of synovial fluid from the ad libitum-fed broilers contained blood.

Animal Husbandry↗

Progressive resistance strength training for physical disability in older people.

BACKGROUND: Muscle weakness in old age, is associated with physical disability and an increased risk of falls. Progressive resistance strength (PRT) training exercises (i.e. movements performed against a specific external force that is regularly increased during training) are designed to increase strength in older people. OBJECTIVES: To assess the effect of PRT on measures of physical disability, functional limitation and impairment in older people, and identify adverse events. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialized register (to August 2002), CENTRAL/CCTR (The Cochrane Library Issue 2, 2002), MEDLINE (1966 to February 1, 2002), EMBASE (1980 to February 1, 2002), CINAHL (1982 to February 1, 2002), Sports Discus (1948 to February 1, 2002), PEDro - The Physiotherapy Evidence Database (accessed February 1, 2002) and Digital Dissertations (accessed February 1, 2002). We also searched reference lists of articles, reviewed conference abstracts and contacted authors. SELECTION CRITERIA: Randomised trials of PRT alone for older people (i.e. mean age of 60 or over) were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Weighted mean differences (WMD) were obtained using fixed or random effect models as appropriate. When measures with different units were pooled, standardised mean differences (SMD) were calculated. Relative risks were calculated for dichotomous outcomes. MAIN RESULTS: Sixty-six trials with 3783 participants were included. Most studies were small and of poor quality. PRT had a large positive effect on strength (41 trials, 1955 participants), but there was statistical heterogeneity that was not explained by differences in study quality, participant characteristics or the exercise program. Some functional limitation measures showed modest improvements (i.e. gait speed, 14 trials, 798 participants, WMD 0.07 m/s, 95% CI 0.04 to 0.09). However, there was no evidence that PRT had an effect on physical disability when activity measures or health related quality of life measures (HRQOL) were assessed (10 trials, 798 participants, SMD 0.01, 95% CI -0.14 to 0.16 ). Adverse events were poorly recorded, but musculoskeletal injuries were detected in most of the studies that prospectively defined and monitored these events. REVIEWER'S CONCLUSIONS: PRT appears to be an effective intervention to increase strength in older people and has a positive effect on some functional limitations. However, the effect of this intervention on more substantive outcomes such as measures of disability or HRQOL remains unclear. It is difficult to determine the balance of risks and benefits of PRT because adverse events have generally been poorly collected and recorded.

Aged↗

Direct lung delivery of para-aminosalicylic acid by aerosol particles.

Para-aminosalicylic acid (PAS), a tuberculostatic agent, was formulated into large porous particles for direct delivery into the lungs via inhalation. These particles possess optimized physical properties for deposition throughout the respiratory tract, a drug loading of 95% by weight and physical stability over 4 weeks at elevated temperatures. Upon insufflation in rats, PAS concentrations were measured in plasma, lung lining fluid and homogenized whole lung tissue. Systemic drug concentrations peaked at 15 min, with a maximum plasma concentration of 11+/-1 microg/ml. The concentration in the lung lining fluid was 148+/-62 microg/ml at 15 min. Tissue concentrations were 65+/-20 microg/ml at 15 min and 3.2+/-0.2 microg/ml at 3h. PAS was cleared within 3 h from the lung lining fluid and plasma but was still present at therapeutic concentrations in the lung tissue. These results suggest that inhalation delivery of PAS can potentially allow for a reduction in total dose delivered while providing for higher local and similar peak systemic drug concentrations as compared to those obtained upon oral PAS dosing. Similar particles could potentially be used for the delivery of additional anti-tuberculosis agents such as rifampicin, aminoglucosides or fluoroquinolones.

Administration, Inhalation↗

Molecular epidemiology of group B streptococci in Ireland: associations between serotype, invasive status and presence of genes encoding putative virulence factors.

Group B streptococcal isolates (n = 159) from the three Dublin maternity hospitals, were serotyped and analysed for the bac, bca, hylB, pepB, and rib genes. The serotype distribution of the isolates was Ia, 19.5%; Ib, 18.9%; II, 10.7%; III, 29.5%; IV, 1.9%; V, 15.1%; non-typeable, 4.4%. There was a statistically significant association between the serotype and invasive status (carriage or infection) of isolates (P < 0.005), but no significant association between serotype and degree of invasiveness was demonstrated. The presence or absence of each analysed gene was not associated with the invasive status of isolates. Statistically significant associations were revealed between bca and hylB (IS1548) (P = 0.0004) and between bac and bca (P=0.014). The bac, bca, hylB (IS1548) and rib genes and the numbers of tandem repeats in the bca gene showed significant associations with serotype. Almost 50% of serotype III isolates possessed at least one of the bac and bca genes and 55-65% of strains of serotypes Ia, Ib and II possessed the rib gene. Most serotype III isolates had IS1548 in their hylB genes. Serotype Ib was the only serotype in which more than half of the strains contained more tandem repeats in the bca gene than the overall mean for the GBS population studied of 7.4 repeats. These findings indicate that some previously reported associations between putative virulence factors and GBS disease require further study and clarification.

Chi-Square Distribution↗

Fracture of the proximal tibial epiphysis and tuberosity in 10 dogs.

Ten dogs were presented with fractures of the proximal tibial epiphysis and tuberosity. All dogs had a cranioproximal-caudodistal angulation of the tibial plateau. Six dogs had marked caudal displacement of the proximal tibial epiphysis, five of which had also sustained fractures of the proximal fibula. The estimated mean angle of inclination of the tibial plateau of affected limbs was 45.8 +/- 9.6 degrees, which was significantly greater (P<0.0005) than the estimated mean angle of the normal contralateral limb 26.2 +/- 6.6 degrees. The mean angle of inclination of the tibial plateau of dogs with fibular fractures (n=5) was not significantly different from dogs without fibular fractures (n=5) (P>0.25). Five dogs were treated conservatively and five were treated by three different methods of surgical repair. Surgically treated dogs had significantly greater preoperative tibial plateau angles (P<0.05). All dogs regained full limb usage, regardless of the method of treatment chosen.

Animals↗

Penicillin susceptibility and epidemiological typing of invasive pneumococcal isolates in the Republic of Ireland.

A national study was undertaken to investigate the incidence of invasive pneumococcal disease in the Republic of Ireland and to examine the associated isolates. In 1999, 144 S. pneumoniae isolates, all recovered from cases of invasive disease, were received from 12 microbiology laboratories. The incidence of invasive pneumococcal disease was estimated to be 6.6/100000 population. All isolates were analyzed for serotype, penicillin susceptibility, chromosomal relatedness (by using pulsed-field gel electrophoresis [PFGE]), and penicillin-binding protein (pbp) fingerprinting. Several findings of note were observed regarding the pneumococcal population in Ireland. First, isolates of 25 different serotypes were represented, with serotypes 14, 9V, 8, 5, 4, and 3 being the most common. This finding, together with the pbp fingerprinting and PFGE typing results, indicated the clonal spread of strains of these serotypes in Ireland. Second, 27 (18.7%) isolates had reduced susceptibility to penicillin, and 74% of these were serotype 9V. Of these, 80% appeared to belong to the same clone. This could suggest the spread of the international Spanish/French 9V penicillin-resistant clone into Ireland. Third, nine different pbp genotypes were identified, four of which were new. Two pbp genotypes accounted for the majority of isolates dividing them according to their penicillin susceptibility status but irrespective of serotype and PFGE type. This is strong evidence for the occurrence of horizontal transfer of pbp genes between strains, observed with both penicillin-susceptible and penicillin-nonsusceptible isolates. Fourth, there was evidence of serotype transformation since isolates, indistinguishable by pbp fingerprinting and PFGE typing, expressed different capsular types.

Base Sequence↗

Trojan particles: large porous carriers of nanoparticles for drug delivery.

We have combined the drug release and delivery potential of nanoparticle (NP) systems with the ease of flow, processing, and aerosolization potential of large porous particle (LPP) systems by spray drying solutions of polymeric and nonpolymeric NPs into extremely thin-walled macroscale structures. These hybrid LPPs exhibit much better flow and aerosolization properties than the NPs; yet, unlike the LPPs, which dissolve in physiological conditions to produce molecular constituents, the hybrid LPPs dissolve to produce NPs, with the drug release and delivery advantages associated with NP delivery systems. Formation of the large porous NP (LPNP) aggregates occurs via a spray-drying process that ensures the drying time of the sprayed droplet is sufficiently shorter than the characteristic time for redistribution of NPs by diffusion within the drying droplet, implying a local Peclet number much greater than unity. Additional control over LPNPs physical characteristics is achieved by adding other components to the spray-dried solutions, including sugars, lipids, polymers, and proteins. The ability to produce LPNPs appears to be largely independent of molecular component type as well as the size or chemical nature of the NPs.

Biocompatible Materials↗

Cognition and the inhibitory control of saccades in schizophrenia and Parkinson's disease.

Historically, various lines of evidence have converged on the view that the brain expends much of its neural resources on inhibiting its own activity in a critical step towards the cognitive control of behaviour. The loss of inhibitory control is widely reported in neurological and psychiatric disorders; however, the consequences of reduced inhibition in terms of wider cognitive effects on cognitive control operations such as planning, abstract thought, working memory and the ability to appreciate the perspective of others ('theory of mind') has been widely overlooked. The antisaccade paradigm examines the conflict between a prepotent stimulus that produces a powerful urge to fixate the target, and the overriding goal to 'look' in the opposite direction. In this chapter we illustrate how this paradigm is increasingly used to explore the relationship of inhibitory control and cognition in Parkinson's disease, schizophrenia and healthy participants. Evidence is presented that is consistent with the theory of cognitive inhibition as a distinct process that can be dissociated from working memory. We conclude that the inhibitory control of saccadic eye movement should be studied in the wider context of cognitive operations.

Cognition↗

Extensive interbreed, but minimal intrabreed, variation of DLA class II alleles and haplotypes in dogs.

The DLA class II genes in the dog major histocompatibility complex are highly polymorphic. To date, 52 DLA-DRB1, 16 DLA-DQA1 and 41 DLA-DQB1 allelic sequences have been assigned. The aim of this study was to examine the intrabreed and interbreed variation of DLA allele and haplotype frequencies in dogs, and to ascertain whether conserved DLA class II haplotypes occur within and between different breeds. One thousand and 25 DNA samples from over 80 different breeds were DLA class II genotyped, the number of dogs per breed ranging from 1 to 61. DNA sequence based typing and sequence specific oligonucleotide probing were used to characterize dogs for their DLA-DRB1, DQA1 and DQB1 alleles. The high frequency of DLA class II homozygous animals (35%), allowed the assignment of many haplotypes despite the absence of family data. Four new DLA alleles were identified during the course of this study. Analysis of the data revealed considerable interbreed variation, not only in allele frequency, but also in the numbers of alleles found per breed. There was also considerable variation in the number of breeds in which particular alleles were found. These interbreed variations were found in all three DLA class II loci tested, and also applied to the three-locus haplotypes identified. Within this data set, 58 different DLA-DRB1/DQA1/DQB1 three-locus haplotypes were identified, which were all found in at least two different animals. Some of the haplotypes appeared to be characteristic of certain breeds. The high interbreed, and relatively low intrabreed, variation of MHC alleles and haplotypes found in this study could provide an explanation for reports of interbreed variation of immune responses to vaccines, viruses and other infections.

Alleles↗

The influence of shape and sliding distance of femoral head movement loci on the wear of acetabular cups in total hip arthroplasty.

Wear of the polyethylene acetabular component is the most serious threat to the long-term success of total hip replacements (THRs). Greatly reduced wear rates have been reported for unidirectional, compared to multidirectional, articulation in vitro. This study considers the multidirectional motions experienced at the hip joint as described by movement loci of points on the femoral head for individual THR patients. A three-dimensional computer program determined the movement loci of selected points on the femoral head for THR patients and normal subjects using kinematic data obtained from gait analysis. The sizes and shapes of these loci were quantified by their sliding distances and aspect ratios with substantial differences exhibited between individual THR patients. The average sliding distances ranged from 10.0 to 18.1 mm and the average aspect ratios of the loci ranged from 2.5 to 9.2 for the THR patients. Positive correlations were found between wear rate and average sliding distance, the inverse of the average aspect ratio of the loci and the product of the average sliding distance and the inverse of the average aspect ratio of the loci. Patients with a normal hip joint range of motion produce multidirectional motion loci and tend to experience more wear than patients with more unidirectional motion loci. Differing patterns of multidirectional motion at the hip joint for individual THR patients may explain widely differing wear rates in vivo.

Acetabulum↗

Age-related morphometry of equine calcified cartilage.

Although there are many studies in the equine literature focused on articular diseases and the aetiology of osteoarthritis, few have concentrated on normal articular structures and how they change with age. The objective of this investigation was to study the thickness and morphology of the calcified cartilage layer of the distal metacarpus over a range of ages. A parasagittal slab of bone was sectioned from the region of sesamoid contact on the medial condyle of the metacarpi from 34 horses. The slab of bone was preserved, dehydrated and embedded, undecalcified, in methylmethacrylate and then stained with toluidine blue. Six repeatable fields of interest from the distal aspect of each metacarpus were digitised and examined to determine the morphology of the calcified cartilage layer. The thickness of the calcified cartilage, range 88-426 microm, was estimated using a method of integration. The results indicate an age-related influence on the thickness of the calcified cartilage layer, generally increased in older horses. While this finding is significant, perhaps more importantly a positional relationship was also identified, indicating that pressures endured by different regions within a joint may dictate morphological development of the tissues. This study has begun to lay the groundwork to determine whether the calcified layer of the hyaline cartilage could be involved in the development of osteoarthritis.

Age Factors↗

Dog MHC alleles containing the human RA shared epitope confer susceptibility to canine rheumatoid arthritis.

To determine whether canine rheumatoid arthritis (CRA) is associated with dog MHC (DLA-DRB1) alleles which contain the QRRAA/RKRAA conserved third hypervariable region (3HVR) sequence, DNA samples were extracted from 61 dogs with clinically diagnosed small-joint polyarthritis and from 425 controls. Breed-matched controls were available for 41 cases. DLA-DRB1 genotypes were identified using molecular typing methods. Phenotype frequencies were compared between cases and controls and odds ratios with 95% confidence intervals calculated. Several DLA-DRB1 alleles were associated with increased risk for CRA: DLA-DRB1*002, DRB1*009, and DRB1*018. This was also observed for the presence of any shared epitope (SE)-bearing allele. The associations with DLA-DRB1*002 and the SE were maintained when only breed-matched cases and controls were compared. This study suggests that a conserved amino acid motif in the 3HVR present in some DRB1 alleles of both dogs and humans is associated with rheumatoid arthritis in both species.

Alleles↗

Molecular cloning and characterization of canine metalloproteinase-9 gene promoter.

This paper describes the cloning and characterization of the canine matrix metalloproteinase-9 (MMP-9) gene promoter. The 5' untranslated region was obtained by genome walking upstream of the canine MMP-9 translation start site using canine genomic DNA as template. A DNA fragment of 1894 bp was isolated and on analysis demonstrated regions of sequence homology with the MMP-9 promoter sequences already determined for other species. In general, conserved regions correlated with DNA binding motifs such as a TATA-like box, AP-1 sites, GC boxes and a nuclear factor-kappaB binding domain. The DNA promoter fragment was sufficient to drive basal expression of a luciferase reporter gene in Madin Darby canine kidney (MDCK) cells and to a lesser extent in feline embryonic fibroblast (FEA) cells. Activity of the promoter was enhanced by the treatment of transfected MDCK cells with phorbol 12-myristate 13-acetate but no effect was observed in the FEA cells. Promoter deletion studies revealed that regions of promoter were necessary for induction of reporter gene expression.

Amino Acid Sequence↗

Targeting mutants of PTEN reveal distinct subsets of tumour suppressor functions.

The tumour suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a lipid phosphatase which can antagonize the phosphoinositide 3-kinase (PI 3-kinase) signalling pathway, promoting apoptosis and inhibiting cell-cycle progression and cell motility. We show that very little cellular PTEN is associated with the plasma membrane, but that artificial membrane-targeting of PTEN enhances its inhibition of signalling to protein kinase B (PKB). Evidence for potential targeting of PTEN to the membrane through PDZ domain-mediated protein-protein interactions led us to use a PTEN enzyme with a deletion of the C-terminal PDZ-binding sequence, that retains full phosphatase activity against soluble substrates, and to analyse the efficiency of this mutant in different cellular assays. The extreme C-terminal PDZ-binding sequence was dispensable for the efficient down-regulation of cellular PtdIns(3,4,5)P3 levels and a number of PI 3-kinase-dependent signalling activities, including PKB and p70S6K. However, the PDZ-binding sequence was required for the efficient inhibition of cell spreading. The data show that a PTEN mutation, similar to those found in some tumours, affects some functions of the protein but not others, and implicate the deregulation of PTEN-dependent processes other than PKB activation in the development of some tumours. Significantly, this hypothesis is supported by data showing low levels of PKB phosphorylation in a glioblastoma sample carrying a mutation in the extreme C-terminus of PTEN compared with tumours carrying phosphatase-inactivating mutations of the enzyme. Our data show that deregulation of PKB is not a universal feature of tumours carrying PTEN mutations and implicate other processes that may be deregulated in these tumours.

Animals↗

Cloning of canine IL-1ra, TNFR and TIMP-2.

This paper describes the cloning and sequence analysis of the cDNA's encoding the canine homologues of interleukin-1 receptor antagonist (IL-1ra), tumour necrosis factor receptor extra-cellular domain (TNFR/ECD) and tissue inhibitor of metalloproteinase-2 (TIMP-2). The coding sequences for canine IL-1ra and TNFR/ECD were obtained using reverse transcription polymerase chain reaction (RT-PCR) using RNA harvested from canine peripheral blood mononuclear cells (PBMC) and TIMP-2 was isolated in a similar fashion from the canine D17 osteosarcoma cell line. Sequence analysis of the canine genes demonstrated open reading frames of 531, 633 and 663 base pairs (bp), respectively. All three canine proteins IL-1ra, TNFR/ECD and TIMP-2 (177, 211 and 221 amino acids, respectively) showed considerable sequence similarity with the homologous sequences published for other species.

Amino Acid Sequence↗

BETR North America: a regionally segmented multimedia contaminant fate model for North America.

We present the Berkeley-Trent North American contaminant fate model (BETR North America), a regionally segmented multimedia contaminant fate model based on the fugacity concept. The model is built on a framework that links contaminant fate models of individual regions, and is generally applicable to large, spatially heterogeneous areas. The North American environment is modeled as 24 ecological regions, within each region contaminant fate is described using a 7 compartment multimedia fugacity model including a vertically segmented atmosphere, freshwater, freshwater sediment, soil, coastal water and vegetation compartments. Inter-regional transport of contaminants in the atmosphere, freshwater and coastal water is described using a database of hydrological and meteorological data compiled with Geographical Information Systems (GIS) techniques. Steady-state and dynamic solutions to the 168 mass balance equations that make up the linked model for North America are discussed, and an illustrative case study of toxaphene transport from the southern United States to the Great Lakes Basin is presented. Regionally segmented models such as BETR North America can provide a critical link between evaluative models of long-range transport potential and contaminant concentrations observed in remote regions. The continent-scale mass balance calculated by the model provides a sound basis for evaluating long-range transport potential of organic pollutants, and formulation of continent-scale management and regulatory strategies for chemicals.

Air Movements↗