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Biomedical subjects

J Saunders

Publications and source records attributed to J Saunders.

At least 19 recordsLinked to original sources
PubMed2007

Preliminary work on the development of a novel detection method for osteoporosis.

Osteoporosis affects both the organic and mineral phases of bone resulting in a decrease in resistance to fracture. Dual x-ray absorptiometry (DEXA) scans are used for diagnosing osteoporosis, which is conventionally characterised by a decrease in mineral density. Unfortunately, some patients who suffer osteoporotic fractures have normal bone density, because both the organic and the mineral phase are affected. However, there are currently no methods of evaluating the health of the organic phase. Patients undergoing treatment for osteoporosis have reported hardening of their fingernails. As the properties of nail and bone may be linked in a comparable, measurable way, this work used both mechanical (nano-indentation) and chemical (Raman spectroscopy) methods to evaluate differences between fingernails sourced from osteoporotic and non-osteoporotic patients. The difference in mean modulus between the nails sourced from the groups was 1.1 GPa. The disulphide bond content of fingernail samples from each group was measured by Raman spectroscopy and disulphide bond content of fingernail was found to be significantly lower in the osteoporotic group. It can be concluded that a relationship between the mechanical and chemical properties of nail and bone may exist in a measurable way. This work has suggested that changes in the organic phase of bone are reflected in similar proteins, such as keratin, from which fingernails are composed. Collagen and keratin are two distinct structural proteins, but they share the need for protein sulphation and disulphide bond formation, via cysteine, for their structural integrity. A disorder of either process should lead to disordered collagen and keratin synthesis.

Bone Density↗
PubMed2006

Raman spectroscopy of the human nail: a potential tool for evaluating bone health?

Dual X-ray absorptiometry (DEXA) is the current gold standard for the diagnosis of osteoporosis. However, patients can suffer osteoporotic fractures despite normal bone mineral density, partly because of unmeasured influences of both the protein and mineral phases of bone that are affected in osteoporosis. There is currently no clinically applicable method of evaluating the health of the protein phase. The proteins in human nail (keratin) and bone (collagen) require sulphation and disulphide bond (S-S) formation for structural integrity and disorders of either sulphur metabolism or cystathione beta-synthase can lead to structural abnormalities in these tissues. Raman protein spectra provide a method of non-invasive measurement of the degree of sulphation of structurally related proteins that may be indicative of bone health. Raman spectroscopy was used to evaluate the disulphide (S-S) content of fingernails. The nail samples came from from 169 women (84 pre- and 85 post-menopausal), of which 39 had a history of osteoporotic fracture. BMD was measured by DXA at the spine. Analyses included parametric and non-parametric tests, dependent on the distribution of the test variable. Mean disulphide content of the nail reduced with age and was slightly higher in pre-, compared to post-menopausal women (P = 0.187). Significantly lower disulphide content was observed in nails obtained from subjects with a history of fracture (P = 0.025). When either disulphide content or BMD was used as a predictor, the odds ratio of these two measures were found to be comparable predictors for fracture status. This suggests that measurements of change in the protein phase of structural proteins such as keratin in the human nail may be correlated with clinically relevant changes in bone proteins that are important in fracture risk.

Absorptiometry, Photon↗
PubMed2006

Spinodal decomposition in solid isotopic helium mixtures.

We report the first observations of spinodal decomposition in solid helium isotopic mixtures, using NMR measurements. The experiments were performed at a 3He concentration of 50% where the transition proceeds through the critical point. We used an initial pressure such that the system remained solid. Our observations indicate that the transition occurs by the mechanism of spinodal decomposition and we are able to study its evolution in real time.

Journal Article↗
PubMed2006

High latent drug administration error rates associated with the introduction of the international colour coding syringe labelling system.

BACKGROUND AND OBJECTIVES: The potential for increased drug administration errors during the transition to the International Colour Coding syringe labelling system has been highlighted. The purpose of this study was to assess the potential effects before their introduction into our department. METHODS: Thirty-one anaesthetists, 19 with no previous practical experience of the new labelling system (Group 1), and 12 with previous experience (Group 2), volunteered to induce general anaesthesia for a standardized simulated patient in a designated theatre. They were presented with a scenario designed to suggest the need for a rapid sequence induction and provided with drug syringes labelled with the International Colour Coding system. All drug administrations were recorded. Active error was defined as the injection of the wrong drug. Latent error was defined as the selection of a syringe in error but stopping short of administering the drug. RESULTS: In Group 1 a total of 107 drug injections were recorded of which 1 (0.9%) was an active error and 16 (15%) involved latent errors. Eleven anaesthetists (58%) performed at least one latent error. Group 2 had an error rate of 3%, a 6.9 (1.3-26.7) fold reduction in the rate of error (P = 0.023). CONCLUSIONS: Although only one drug was given in active error, latent errors occurred in 15% of drug administrations. The only factor conferring protection against error was prior experience of the new labelling system. The period of transition to the International Colour Coding syringe labelling system represents a time of increased risk of drug administration error.

Adult↗
PubMed2006

True hermaphroditism in six female littermates after administration of synthetic androgens to a pregnant bitch.

A pregnant bitch was treated with a synthetic testosterone mixture on approximately day 40. The female offspring (six pups) showed an increased anogenital distance, vaginal enlargement and a variable amount of vaginal discharge. The urinary orifice was found dorsally in the vestibulum, stooled on a protruding phallus-like structure. All six pups underwent a laparotomy and subsequent spaying and a modified ventral episioplasty technique to lift up the labia to a more vertical position in order to prevent urine accumulation. Histopathological examination of the genital tracts demonstrated the presence of bilateral ovotestis and remnants of the Wolffian duct system in all cases. The finding of true hermaphroditism of the offspring after exogenous androgen administration during gestation of the bitch has not yet been reported elsewhere.

Animals↗
PubMed2005

Premedication for bronchoscopy in older patients: a double-blind comparison of two regimens.

INTRODUCTION: Older patients are the most prevalent age cohort requiring bronchoscopy. Prior sedation should be offered to improve patient comfort and operator technical ease. Older patients have increased sensitivity to centrally acting drugs increasing the procedural risk. This perceived risk may limit access to bronchoscopy in older patients. There have been no systematic prospective placebo-controlled studies in older patients. We compared a novel premedication regimen-oral temazepam plus nebulised Lignocaine (new treatment) to an established regimen of intravenous alfentanyl (control). METHODS: Consecutive patients 75 years and older referred for bronchoscopy were considered. Twenty-five patients were randomly assigned to each group. The primary outcome measure was the lowest oxygen saturation recorded from the administration of IV drugs and for 30 min post-bronchoscopy. RESULTS: The lowest mean oxygen saturation in the new treatment group was 92.2% (90.3-94.2) and in the control group 91.1% (89.2-93.1). This was not statistically different (P = 0.370). There were no adverse events. CONCLUSION: This is the largest prospective study to date on an older population undergoing bronchoscopy supporting previous retrospective findings regarding the safety of this procedure. Determined by oxygen saturations there is no difference in safety between premedication regimens comprising oral temazepam/nebulised lignocaine or intravenous alfentanyl.

Aged↗
PubMed2005

The use of fingernails as a means of assessing bone health: a pilot study.

BACKGROUND: Anecdotally, patients volunteer reports of increasing hardness of their fingernails within months of starting diverse treatments for osteoporosis. The properties of both nail and bone may be linked in a comparable, measurable way. METHODS: We examined the fingernails of two groups of patients, with (n = 9) and without (n = 13) osteoporosis at either the hip or lumbosacral spine. We performed nanoindentation to assess the degree of nail brittleness and Raman spectroscopy to assess the disulfide bond content of nail. RESULTS: The mean moduli of fingernails of patients with low bone mineral density (BMD) are lower than those of patients with normal BMD. The mean difference in mean modulus between the groups was found to be 0.996 (p = 0.15 between groups). The spectroscopy data also showed differences between the two sets of nails. The disulfide bond content of the nails sourced from osteoporotic patients was lower than that from healthy patients (p = 0.06 between groups). CONCLUSIONS: Bone collagen and nail keratin are two distinct structural proteins, and both require protein sulfation and disulfide bond formation, via cysteine, for structural integrity. A disorder of either process may lead to disordered collagen and keratin synthesis. This is reflected in the structural abnormalities seen in clinical syndromes in which there is either protein deficiency, disorders of sulfur metabolism, or cystathione beta-synthase deficiency. The relationship between nail and bone may exist in a measurable way. This pilot study should lead to further work to explore this relationship. Could nail prove to be a valuable adjunct to diagnosis or provide a means of more rapid follow-up after commencement of therapy?

Aged↗
PubMed2005

A review of ENT consultant postal questionnaires.

In recent years, there appears to have been an increase in the number of postal questionnaires being received by ENT consultants. Questionnaires with unsound methodology waste the time of those who send and receive them, as inferences cannot be made from their results. In this study,a review was performed on a sample of 19 questionnaire studies published in two ENT journals between January 1998 and December 2002. Each study was given a 30-point score, based on the quality of its methodology. The average score assigned to each study was 32 percent, suggesting that the quality of methodology was generally poor. These results should serve as a warning to those embarking on and those interpreting research of this kind.

Consultants↗
PubMed2004

Interfacial friction of thin 3He slabs in the Knudsen limit.

A high precision torsional oscillator has been used to study 3He films of thickness from 100 to 350 nm, in the temperature range 5<T<200 mK. This thickness is much smaller than the viscous penetration depth, and also much smaller than the low temperature inelastic mean-free path of 3He quasiparticles. Such films are observed to decouple from the motion of the oscillator below 60 mK. We interpret the frequency shift and dissipation data in terms of an interfacial friction model.

Journal Article↗
PubMed2004

Joint acceleration during gait in relation to age.

Forty-four male and female subjects with no history of falling and whose ages ranged from 10 to 68 years participated in a series of experiments to assess movement at the joints during gait while walking in a straight line, in pivot turns and in turns of 0.33 and 0.66 m diameter. Acceleration at the joints in the forward and side-to-side direction was measured by dual-axis accelerometers placed at the ankles, knees, hips, shoulders, and on the head. Eye movement was assessed from electrodes placed on the sides of the eyes. The results of the experiments showed that for people whose age was above 40 years, significant increases in the forward-back and side-to-side movements occurred at all joints and progressively increased with age. By age 60, adverse movement of the joints as much as quadrupled in many subjects when compared to people whose age was 20-30 years. The increase in joint acceleration occurred equally in the front-back and side-to-side planes. The mechanism of the increased joint movement may be due to tendon laxness, peripheral neuropathy or loss of central control of gait due to age. Accelerometry may be a much more sensitive technique to analyze abnormalities in gait than standard video or observational gait analysis. Results are given as mean (SD) unless otherwise stated.

Acceleration↗
PubMed2004

Gastrointestinal transit time of nondisintegrating radio-opaque pellets in suckling and recently weaned piglets.

The objective was to determine the gastrointestinal (GI) transit times of pellets in piglets at different time points around weaning, as transit times are essential criteria to develop oral drug delivery systems. Nondisintegrating radio-opaque pellets were given orally in order to define the transit times by radiography. The radiographs were analysed with a software programme to calculate the number of pellets present in the different parts of the GI tract. In suckling piglets, the gastric emptying was faster (75% in 1.5 to 3.5 h), and the colonic accumulation (to 73%) was greater than in weaned piglets (3 days, 2 and 3 weeks postweaning, 65% gastric emptying in 18 h, 75% in 17 h, and 75% in 7 h, respectively; maximal colonic accumulations of 48%). Immediately after weaning, the transit was markedly prolonged but shortened with increased postweaning time (3 days, 2 and 3 weeks postweaning, 85% excretion in 175.5, 77, and 50.5 h, respectively). Three weeks postweaning, the transit was no longer affected by weaning as transit times were similar to values reported in growing and adult pigs, and retention appeared to be restricted to the stomach and the colon. These data are of crucial importance in the design of enteric-coated formulations for oral administration of vaccines and therapeutics to young piglets and for human research using the pig model.

Animals↗
PubMed2004

What are local issues? The problem of the local review of research.

Local review of research by ethics committees in the UK has long been held to be an important right of the local research ethics committee and, even with the introduction of the European Clinical Trials Directive, the governance arrangements for research ethics committees continue to allow for local review of multicentre studies. There is no requirement for local review in either the European Union directive or in the guidelines on good clinical practice, and there is little evidence of it anywhere else in Europe. The idea that there can be "local", as opposed to "central" ethical issues in research is an interesting one, which raises important issues about the nature of research ethics and ethical review. The aim of this paper is to argue that there are no such things as local issues in research ethics, and suggest that those questions currently addressed as local issues properly belong within the research governance framework.

Bioethical Issues↗
PubMed2004

Chlamydia trachomatis prevalence in men in the mid-west of Ireland.

OBJECTIVES: To estimate the prevalence of chlamydia infection in young men in the Mid-Western Health Board Region of Ireland, and to determine risk factors for its acquisition. METHODS: Consecutive men attending orthopaedic clinics (OPD), and a university sports arena (UL) were recruited to a chlamydia prevalence study. All men aged 17-35 who had been sexually active and had not passed urine in the last hour were eligible. Information about chlamydia was given, informed consent obtained, and a self administered questionnaire was completed. A first void urine (FVU) was collected and tested by ligase chain reaction (LCR). RESULTS: 82% (207/252) of men from OPD, and 60% (186/310) from UL participated. 6.3% (13/207) from the OPD and 5.4% (10/186) from UL tested LCR positive, giving an overall prevalence of 5.9% (23/393). Proved risk factors for chlamydial positivity were: (1) more than one sexual partner in previous 6 months, (2) more than eight lifetime sexual partners, (3) current symptoms (dysuria or discharge). No statistical significance was found for age, condom use, smoking, days since last sexual intercourse and previous GUM clinic attendance. No statistically significant difference to cost effective prevalence of 6% was shown. CONCLUSIONS: A 5.9% prevalence of Chlamydia trachomatis was found which is cost effective to screen and treat. Non-invasive screening of men in the community was possible. Numbers of sexual partners and current symptoms were significant risk factors. Since only 25% of men in this laboratory were diagnosed with chlamydia outside the GUM clinic, compared with 59% of women, it is important that community screening of men is promoted.

Adolescent↗
PubMed2003

Evidence for a Mott-Hubbard transition in a two-dimensional 3He fluid monolayer.

The heat capacity and magnetization of a fluid 3He monolayer adsorbed on graphite plated with a bilayer of HD have been measured in the temperature range 1-60 mK. Approaching the density at which the monolayer solidifies into a sqrt[7]xsqrt[7] commensurate solid, we observe an apparent divergence of the effective mass and magnetization corresponding to a T=0 Mott-Hubbard transition between a 2D Fermi liquid and a magnetically disordered solid. The observations are consistent with the Brinkman-Rice-Anderson-Vollhardt scenario for a metal-insulator transition. We observe a leading order T2 correction to the linear term in heat capacity.

Journal Article↗
PubMed2003

A glycine to aspartic acid substitution of COL2A1 in a family with the Strudwick variant of spondyloepimetaphyseal dysplasia.

BACKGROUND: Spondyloepimetaphyseal dysplasia (SEMD) is one of a clinically heterogeneous group of skeletal disorders, characterized by defective growth and modelling of the spine and long bones. Common clinical features include disproportionate short stature, malformed vertebrae and abnormal epiphyses or metaphyses. Some cases have been associated with mutations in the COL2A1 gene. AIM: To determine whether the autosomal dominant Strudwick-type SEMD in a three-generation family, showing specific phenotypical features such as chest deformity, limb shortening, myopia and early-onset degenerative osteoarthrosis, might be caused by a novel COL2A1 mutation. DESIGN: Genetic testing and clinical examination of family members. METHODS: Direct sequencing of PCR-amplified genomic DNA from the COL2A1 gene. RESULTS: A point mutation within exon 20 of the COL2A1 gene was identified that substituted a glycine for an aspartic acid residue at codon 262. DISCUSSION: All previously reported autosomal dominant mutations causing SEMD have substituted an obligate glycine within the triple helix, in particular at codons 292, 304 and 709 in the three reported Strudwick-type patients. Additionally, a recurrent glycine substitution at codon 154 has been identified in two unrelated Finnish cases with radiological features consistent with the Strudwick subtype. Our sixth helical glycine substitution extends the mutational spectrum and genotype/phenotype correlations of Strudwick-type SEMD.

Aspartic Acid↗
PubMed2003

Resolution of chylothorax after resection of rib chondroma in a dog.

A six-year-old, male dobermann was presented with a history of dyspnoea and bouts of coughing. Radiography and computed tomography of the thorax showed pleural effusion and a well-circumscribed, calcified mass of 10 cm in diameter, appearing to originate from the left first rib. Thoracocentesis revealed that the pleural fluid was chylous in nature. An incisional biopsy was performed, which gave a histological diagnosis of chondroma. Resolution of the chylothorax after en-bloc surgical removal of the tumour suggested that the rib tumour was the initiating cause of the chylothorax. Seventeen months later, rib neoplasia recurred without pleural effusion, and was removed successfully. To the authors' knowledge, rib chondroma, which is an unusual tumour in dogs, has not been previously documented as a cause of chylothorax.

Animals↗
PubMed2001

4-Hydroxy-5,6-dihydropyrones as inhibitors of HIV protease: the effect of heterocyclic substituents at C-6 on antiviral potency and pharmacokinetic parameters.

Due largely to the emergence of multi-drug-resistant HIV strains, the development of new HIV protease inhibitors remains a high priority for the pharmaceutical industry. Toward this end, we previously identified a 4-hydroxy-5,6-dihydropyrone lead compound (CI-1029, 1) which possesses excellent activity against the protease enzyme, good antiviral efficacy in cellular assays, and promising bioavailability in several animal species. The search for a suitable back-up candidate centered on the replacement of the aniline moiety at C-6 with an appropriately substituted heterocyle. In general, this series of heterocyclic inhibitors displayed good activity (in both enzymatic and cellular tests) and low cellular toxicity; furthermore, several analogues exhibited improved pharmacokinetic parameters in animal models. The compound with the best combination of high potency, low toxicity, and favorable bioavailabilty was (S)-3-(2-tert-butyl-4-hydroxymethyl-5-methyl-phenylsulfanyl)-4-hydroxy-6-isopropyl-6-(2-thiophen-3-yl-ethyl)-5,6-dihydro-pyran-2-one (13-(S)). This thiophene derivative also exhibited excellent antiviral efficacy against mutant HIV protease and resistant HIV strains. For these reasons, compound 13-(S) was chosen for further preclinical evaluation.

Animals↗