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Biomedical subjects

R K Smith

Publications and source records attributed to R K Smith.

At least 19 recordsLinked to original sources

Microdisplacement printing.

We describe a new patterning technique that employs microcontact printing to replace preformed labile self-assembled monolayers (SAMs) selectively; we call this "microdisplacement printing". We demonstrate that this technique results in ordered molecular regions of both the patterning ("displacing") molecule as well as the remnant labile film, here 1-adamantanethiolate. The existence of the 1-adamantanethiolate SAM before patterning hinders lateral surface diffusion of the patterning molecules, and therefore permits the use of molecules that are otherwise too mobile to pattern by other methods.

Journal Article↗

Effect of age at presentation on outcome following arthroscopic debridement of subchondral cystic lesions of the medial femoral condyle: 85 horses (1993--2003).

REASONS FOR PERFORMING STUDY: Subchondral cystic lesions of the medial femoral condyle (SCMFC) are well documented in horses < or =3 years; arthroscopic debridement or enucleation of the cyst is currently the surgical treatment of choice. However, studies of occurence and outcome following surgery in older horses are lacking. OBJECTIVE: To identify factors important in outcome for horses with SCMFC treated by arthroscopic debridement. HYPOTHESIS: Age of horse at presentation has a significant influence on return to work following arthroscopic treatment for SCMFC. Clinical and diagnostic findings are also significant with respect to prognosis. METHODS: A retrospective review of medical records from 6 equine referral centres identified 85 horses that underwent arthroscopic debridement of SCMFC. Clinical examination, radiographic and arthroscopic findings were analysed together with follow-up data. Univariable analysis and multivariable logistic regression models were used to determine factors affecting return to soundness. Event-time analysis was performed to evaluate return to work. RESULTS: Older horses (>3 years) were less likely to return to soundness (P = 0.02) or to work (P = 0.04) than younger horses (< or = 3 years). Of 39 horses age 0-3 years, 25 (64%, 95% CI 49-79%) returned to soundness. Of 46 horses age >3 years, 16 (35%,95% CI 21-49%) returned to soundness. In addition, cartilage damage at sites other than the SCMFC negatively affected prognosis (P = 0.05). The hospital where treatment was performed had no influence on return to soundness. CONCLUSIONS: Older horses carry a worse prognosis for both return to soundness and return to work. POTENTIAL RELEVANCE: It is important for clients to be made aware of the difference in outcome between age groups.

Age Factors↗

Healthy and pre-eclamptic placental basal plate lining cells: quantitative comparisons based on confocal laser scanning microscopy.

Immunocytochemical confocal laser scanning microscope images of the monolayer of cells lining the intervillus space at the basal plate of term placentae were analysed using stereology. Immunoreactively-distinct regions of this mosaic layer were measured. In basal plate from healthy pregnancies, trophoblast epithelium occupied 18.91% of the surface area and endothelium 60.81%. In pre-eclampsia the equivalent areas were 15.57% and 67.63%. Acellular fibrinoid covers the remaining area and this component decreases in area in pre-eclampsia. The statistically significant increase in the cellular endothelial compartment may be relevant to the hypertensive pathology of pre-eclampsia as endothelial signalling plays a major role in regulation of blood pressure.

Endothelial Cells↗

Confocal laser scanning microscope study of cytokeratin immunofluorescence differences between villous and extravillous trophoblast: cytokeratin downregulation in pre-eclampsia.

Pre-eclampsia is a disease characterized by failures in interstitial implantation. One product of the implantation process is the basal plate; a structure whose complexity makes it hard to fully appreciate the pathological changes in significant diseases of pregnancy. This article describes our use of CLSM immunofluorescence to examine the cytokeratin composition of the cells of trophoblastic origin in the term placental basal plate. Large differences in the content of the structural polymeric protein were compared using analysis of digital images. We show that greater pancytokeratin immunofluorescence is observed in extravillous cytotrophoblast cells as compared with villous trophoblast. There is a >30-fold difference in the mean area percent of the most intensely immunofluorescent pixels in the tissue containing these cells. This is a very high, statistically significant difference as defined by the Wilcoxon Signed Ranks Test Asym. Sig. (two-tailed): P < 0.001. The most invasive population of cells of the trophoblast lineage (the extravillous trophoblast) exhibits a significant reduction in cytokeratin immunofluorescence when comparisons of healthy and pre-eclamptic pregnancies are made. This ratio was 2.4:1. It was tested using the Mann-Whitney U-test. From healthy to pre-eclamptic the reduction was from mean rank 83.42((healthy)) to 51.13((pre-eclamptic)). The difference was very highly statistically significant (n = 53 + 75 = 128; U = 984.500; Z = -4.852; P < 0.001). There was also less cytokeratin-related immunofluorescence in villous trophoblast when healthy villi were compared with pre-eclamptic villi. The observed alterations in trophoblastic cytoskeletal components are expected to damage the anchorage and motility of cells. The extravillous trophoblast is known to be necessary for implantation. This leads to a cellular hypothesis of the failure of implantation resulting in reduced depth of uterine invasion and failure to adapt the spiral arterioles for low-pressure perfusion of the intervillus space, two well-known features of pre-eclampsia. The reduction in cytokeratin-related immunofluorescence in the villus trophoblast seen on comparing healthy term placentae with those from pre-eclamptics implies that the trophoblast is a weaker epithelial layer in the hypertensive pregnancy. This could account for the rise in deported trophoblast associated with pre-eclampsia. Deported trophoblast has been invoked as the systemic messenger that leads to generalized maternal hypertension seen in this condition.

Cell Differentiation↗

Retrospective study of 24 cases of septic calcaneal bursitis in the horse.

REASONS FOR PERFORMING STUDY: Wounds to the plantar aspect of the tarsus present a diagnostic and treatment challenge. This study was undertaken to describe specific features of traumatic wounds involving the calcaneal bursa, with a view to determining which clinical examination findings and diagnostic tests results could provide reliable indicators of prognosis. OBJECTIVES: To report clinical presentation, diagnostic findings, treatment and outcome of 24 cases of septic calcaneal bursitis; and to determine the importance of the involvement of specific anatomical structures in relation to the prognosis for survival and return to athletic function. METHODS: Records of 24 horses that had suffered traumatic wounds involving the calcaneal bursae were reviewed and divided into 3 groups, based on the bursa involved and presence or absence of involvement of the tuber calcanei. Clinical, diagnostic imaging and surgical findings were recorded for each case. Differences between groups and outcome were examined for significance with Chi-squared, Fisher's Exact or Kruskal-Wallis tests, as appropriate. RESULTS: Wounds involving only the subcutaneous bursa had an excellent prognosis for survival. Seventy-five percent of horses with wounds involving the intertendinous calcaneal bursa survived. Involvement of the tuber calcanei presented a fair to guarded prognosis, with only 44% of horses with involvement of this structure surviving. CONCLUSIONS: In contrast to other studies of septic synovial structures, the time between initial injury and referral did not affect the outcome. Correct identification of invasion of the calcaneal bursa(e) and/or tuber calcanei in wounds to the plantar aspect of the tarsus allows for more accurate pronostication. Damage to the tuber calcanei presents a poorer prognosis than for cases that involve only the soft tissue structures in the region. POTENTIAL RELEVANCE: This study demonstrates the importance of correct anatomical identification of structures involved in wounds in the region of the calcaneal bursa. The use of radiography, ultrasonography and synoviocentesis are essential in these cases to provide the most appropriate treatment for the horse and accurate prognosis for the owner.

Animals↗

Use of a bioabsorbable implant for the repair of severed digital flexor tendons in four horses.

A new bioabsorbable implant composed of poly-L-lactic acid was used to repair the severed digital flexor tendons of four horses. The limbs were immobilised with distal casts which were changed after six to eight weeks and removed after 12 to 16 weeks. The horses were followed clinically and ultrasonographically for from seven to 19 months after the surgery. The ultrasonographic examination after the cast had been removed showed that the implants had been well incorporated into scar tissue. Two of the horses were mildly lame at the trot seven months after the surgery, but had returned to work after 12 months. The other two horses are still lame. No complications were observed with the implant.

Absorbable Implants↗

Treatment of sepsis in the small tarsal joints of 11 horses with gentamicin-impregnated polymethylmethacrylate beads.

Gentamicin-impregnated polymethylmethacrylate beads were used to treat infective arthritis in the small tarsal joints of 11 severely lame horses. Under general anaesthesia, between five and 10 beads were placed into a 7 to 8 mm tract drilled across the affected joint and, in all except one horse, they were left in place for 14 days. Two of the horses were euthanased for reasons other than persistent tarsal joint sepsis, but the other nine survived and seven of them returned to their previous level of athletic performance.

Animals↗

The distribution of cartilage oligomeric matrix protein (COMP) in equine carpal articular cartilage and its variation with exercise and cartilage deterioration.

Based on previous studies where tendons receiving the most load have been shown to have the highest levels of cartilage oligomeric matrix protein (COMP), we hypothesized that COMP distribution in articular cartilage may be influenced by mechanical loading. This investigation aimed (a) to describe the pattern of COMP immunoreactivity in middle carpal joint cartilage of two-year-old Thoroughbred horses; (b) to determine topographical variations; (c) to compare high (group 1) and low (group 2) intensity training and (d) to describe COMP immunoreactivity at sites with early osteoarthritis. Group 1 (n =6) underwent a 19 week high-intensity treadmill training programme and group 2 (n =6) were given daily walking until euthanasia. Dorsal and palmar sites on radial and third carpal articular surfaces were prepared. Immunohistochemistry was performed with polyclonal rabbit anti-equine COMP antiserum using a biotin-streptavidin/peroxidase method. Results showed: (a) intracellular immunoreactivity was present in all cartilage zones, but the distribution of COMP staining within the matrix varied between cartilage zones; (b) differences in distribution between sites were not observed, but total COMP levels in exercised horses (n =2) did vary between sites with dorsal sites containing less COMP than palmar sites on the radial, intermediate and third carpal lateral facet; (c) group 1 cartilage showed marked interterritorial distribution in the deep layer compared to group 2 where staining was more generalized throughout the matrix and (d) fibrillated cartilage showed increased local immunoreactivity in the matrix. These findings demonstrate zonal variations in equine COMP distribution which may be influenced by loading.

Animals↗

The Arabidopsis dnd1 "defense, no death" gene encodes a mutated cyclic nucleotide-gated ion channel.

Gene-for-gene disease resistance typically includes a programmed cell death response known as the hypersensitive response (HR). The Arabidopsis thaliana dnd1 mutant was previously isolated as a line that failed to produce the HR in response to avirulent Pseudomonas syringae pathogens; plants homozygous for the recessive dnd1-1 mutation still carry out effective gene-for-gene resistance. The dnd1-1 mutation also causes constitutive systemic resistance and elevated levels of salicylic acid. In the present study, a positional cloning approach was used to isolate DND1. DND1 encodes the same protein as AtCNGC2, a cyclic nucleotide-gated ion channel of previously unknown organismal function that can allow passage of Ca(2+), K(+) and other cations [Leng, Q., Mercier, R. W., Yao, W. & Berkowitz, G. A. (1999) Plant Physiol. 121, 753-761]. By using a nahG transgene, we found that salicylic acid is required for the elevated resistance caused by the dnd1 mutation but that removal of salicylic acid did not completely eliminate the dwarf and loss-of-HR phenotypes of mutant dnd1 plants. A stop codon that would severely truncate the DND1 gene product was identified in the dnd1-1 allele. This demonstrates that broad-spectrum disease resistance and inhibition of the HR can be activated in plants by disruption of a cyclic nucleotide-gated ion channel.

Arabidopsis↗

Sequence heteroplasmy of D-loop and rRNA coding regions in mitochondrial DNA from Holstein cows of independent maternal lineages.

A mitochondrial DNA (mtDNA) fragment containing the D-loop, phenylalanine tRNA, valine tRNA, and 12S and 16 rRNA genes was cloned and sequenced from 36 cows of 18 maternal lineages to identify the polymorphic sites within those regions and to detect the existence of heteroplasmic mtDNA in cows. Seventeen variable sites were observed within the D-loop and rRNA coding regions of bovine mtDNA within a 2.5-kb span. The hypervariable sites in the D-loop and rRNA coding regions were identified at nucleotide positions 169, 216, and 1594. Heteroplasmic mtDNA (variable mtDNA within a tissue) existed extensively in cows and was detected within the above regions in 11 of 36 cows sequenced. The insertion, deletion, and nucleotide transversion polymorphisms were found only in homopolymer regions. Heteroplasmy was observed frequently and seemingly is persistent in cattle. Though heteroplasmy was demonstrated, most lineages and mtDNA sites showed no heteroplasmy.

Animals↗

Superficial digital flexor tendonitis in the horse.

The superficial digital flexor tendon (SDFT) is an elastic structure that during maximal exercise appears to operate close to its functional limits. The biomechanical and biochemical responses to exercise, injury, and healing are still poorly understood but ongoing research is providing valuable new information which is addressed in this review. It appears that the SDFT matures early, after which time it has limited ability to adapt to stress and undergoes progressive degeneration. Focal hypocellularity, collagen fibril degeneration, selective fibril loading and alterations in the noncollagenous matrix occur primarily within the central core region of the midmetacarpal segment. Current treatment strategies have had equivocal results in returning animals to optimal athletic activity. To date it would seem that progressive rehabilitation programmes coupled with regular ultrasonographic evaluations are a cost-effective and comparable strategy when compared to surgical treatment methods. Recent interest in pharmacological modulation of intrinsic healing of collagenous structures has led to the investigation of various growth factors as potential therapeutic aids in the healing of tendon injuries. However, one of the major goals in tendon research, and one which holds the most optimism for success in the immediate future, is the prevention of tendon injuries.

Animals↗

Cartilage oligomeric matrix protein (COMP) levels in digital sheath synovial fluid and serum with tendon injury.

Cartilage oligomeric matrix protein (COMP) is a noncollagenous extracellular matrix protein found predominantly in cartilage, but also in tendon, ligament and meniscus. Studies in man have demonstrated that it may be used as a prognostic marker in rheumatoid arthritis and osteoarthritis. The present study investigated whether tendon injury contributes to serum and tendon sheath synovial fluid levels of COMP in horses. COMP levels, analysed by competitive ELISA, in the digital sheath synovial fluid were more than 10-fold higher than in the serum. Levels were significantly raised when tendon damage or sepsis was present within the tendon sheath but showed only mild, statistically insignificant, elevation in cases of tenosynovitis alone. COMP concentrations in serum were found to vary with age. Foals (age < or = 1 year) had significantly (P<0.001) higher levels in comparison to older control horses. Total COMP concentrations in an age-matched group with tendinitis were not significantly different from the control group. Measurements of COMP levels in tendon sheath synovial fluid are therefore useful in depicting processes in tendon tissue, while elevated serum levels are likely to be more representative of joint disease than tendinitis.

Age Factors↗

Federation of the Person Identification Service between enterprises.

The Person Identification Service (PIDS) is a standard that has been adopted by the Object Management Group for managing identities of persons within a particular domain. That standard includes an interface that supports the ability to connect multiple PIDS servers together in a federated manner. The specification leaves great flexibility as to how to accomplish the federation. In this paper, we examine some of the federated approaches being considered by the Government Computer-based Patient Record Framework (G-CPR) project and discuss their advantages and disadvantages and the details of a specific, scalable approach to federation.

Government Agencies↗