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Biomedical subjects

G D Smith

Publications and source records attributed to G D Smith.

At least 19 recordsLinked to original sources
PubMed2006

Li+ transport in lithium sulfonylimide-oligo(ethylene oxide) ionic liquids and oligo(ethylene oxide) doped with LiTFSI.

The Li+ environment and transport in an ionic liquid (IL) comprised of Li+ and an anion of bis(trifluoromethanesulfonyl)imide anion (TFSI-) tethered to oligoethylene oxide (EO) (EO(12)TFSI-/Li+) were determined and compared to those in a binary solution of the oligoethylene oxide with LiTFSI salt (EO(12)/LiTFSI) by using molecular dynamics (MD) simulations and AC conductivity measurements. The latter revealed that the AC conductivity is 1 to 2 orders of magnitude less in the IL compared to the oligoether/salt binary electrolyte with greater differences being observed at lower temperatures. The conductivity of these electrolytes was accurately predicted by MD simulations, which were used in conjunction with a microscopic model to determine mechanisms of Li+ transport. It was discerned that structure-diffusion of the Li+ cation in the binary electrolyte (EO(12)/LiTFSI-) was similar to that in EO(12)TFSI-/Li+ IL at high temperature (>363 K), thus, one can estimate conductivity of IL at this temperature range if one knows the structure-diffusion of Li+ in the binary electrolyte. However, the rate of structure-diffusion of Li+ in IL was found to slow more dramatically with decreasing temperature than in the binary electrolyte. Lithium motion together with EO(12) solvent accounted for 90% of Li+ transport in EO(12)/LiTFSI-, while the Li+ motion together with the EO(12)TFSI- anion contributed approximately half to the total Li+ transport but did not contribute to the charge transport in IL.

Journal Article↗
PubMed2006

Glass transition in 1,4-polybutadiene: Mode-coupling theory analysis of molecular dynamics simulations using a chemically realistic model.

We present molecular dynamics simulations of the glass transition in a chemically realistic model of 1,4-polybutadiene (PBD). Around 40 K above the calorimetric glass transition of this polymer the simulations reveal a well-developed two-stage relaxation of all correlation functions. We have analyzed the time-scale separation between vibrational degrees of freedom (subpicosecond dynamics) and the alpha relaxation behavior (nanosecond to microsecond dynamics) using the predictions of mode-coupling theory (MCT). Our value for the mode-coupling critical temperature Tc agrees perfectly with prior experimental estimates for PBD. The predictions of MCT for the scaling behavior of the so-called beta relaxation, the plateau regime separating vibrational dynamics and the alpha relaxation, are well fulfilled. Furthermore, we are able to derive a consistent set of MCT exponents, completely characterizing the scaling behavior of relaxation processes in the vicinity of Tc. For the temperature dependence of the alpha relaxation we find deviations from MCT predictions which we trace to the influence of torsional barriers on the atomic motions.

Journal Article↗
PubMed2006

Thermal desorption of hydrogen from carbon nanosheets.

Carbon nanosheets are a unique nanostructure that, at their thinnest configuration, approach a single freestanding graphene sheet. Temperature desorption spectroscopy (TDS) has shown that the hydrogen adsorption and incorporation during growth of the nanosheets by radio frequency plasma-enhanced chemical vapor deposition are significant. A numerical peak fitting to the desorption spectra (300-1273 K) via the Polanyi-Wigner equation showed that desorption followed a second order process, presumably by the Langmuir-Hinshelwood mechanism. Six peaks provide the best fit to the TDS spectra. Surface desorption activation energies were determined to be 0.59, 0.63, and 0.65 eV for the external graphite surface layers and 0.85, 1.15, and 1.73 eV for desorption and diffusion from the bulk. In contrast to TDS data from previously studied a-C:H films [Schenk et al. J. Appl. Phys. 77, 2462 (1995)], a greater amount of hydrogen bound as sp(2) hybridized carbon was observed. A previous x-ray diffraction study of these films has shown a significant graphitic character with a crystallite dimension of L(a)=10.7 nm. This result is consistent with experimental results by Raman spectroscopy that show as-grown carbon nanosheets to be crystalline as commercial graphite with a crystallite size of L(a)=11 nm. Following TDS, Raman data indicate that the average crystallite increased in size to L(a)=15 nm.

Journal Article↗
PubMed2005

Histoplasmosis infection presenting as an isolated subcutaneous periarticular upper limb swelling in the immunosuppressed patient.

Atypical mycobacterial and fungal infections may occur in immunosuppressed patients. The impaired host response can make the clinical presentation atypical. Blood and tissue cultures may be negative in the acute phase of the illness, which can lead to a delay in diagnosis. In those patients with AIDS or other underlying immunosuppressive conditions, histoplasmosis cannot always be eradicated, but treatment that achieves chronic suppression may be adequate to maintain functional capacity. This report describes two immunosuppressed patients who presented with isolated subcutaneous histoplasmosis infection around the wrist.

Adult↗
PubMed2005

An improvised depth gauge using a hypodermic needle.

A simple solution to the problem of a broken depth gauge is suggested. A hypodermic needle is bent to simulate the shape of a depth gauge and used in a similar way. This allows measurement of the screw length against the scale on the set. We would advocate this method only when there is no suitable alternative depth gauge available.

Bone Screws↗
PubMed2004

Identification and characterisation of SB-366791, a potent and selective vanilloid receptor (VR1/TRPV1) antagonist.

Vanilloid receptor-1 (TRPV1) is a non-selective cation channel, predominantly expressed by peripheral sensory neurones, which is known to play a key role in the detection of noxious painful stimuli, such as capsaicin, acid and heat. To date, a number of antagonists have been used to study the physiological role of TRPV1; however, antagonists such as capsazepine are somewhat compromised by non-selective actions at other receptors and apparent modality-specific properties. SB-366791 is a novel, potent, and selective, cinnamide TRPV1 antagonist isolated via high-throughput screening of a large chemical library. In a FLIPR-based Ca(2+)-assay, SB-366791 produced a concentration-dependent inhibition of the response to capsaicin with an apparent pK(b) of 7.74 +/- 0.08. Schild analysis indicated a competitive mechanism of action with a pA2 of 7.71. In electrophysiological experiments, SB-366791 was demonstrated to be an effective antagonist of hTRPV1 when activated by different modalities, such as capsaicin, acid or noxious heat (50 degrees C). Unlike capsazepine, SB-366791 was also an effective antagonist vs. the acid-mediated activation of rTRPV1. With the aim of defining a useful tool compound, we also profiled SB-366791 in a wide range of selectivity assays. SB-366791 had a good selectivity profile exhibiting little or no effect in a panel of 47 binding assays (containing a wide range of G-protein-coupled receptors and ion channels) and a number of electrophysiological assays including hippocampal synaptic transmission and action potential firing of locus coeruleus or dorsal raphe neurones. Furthermore, unlike capsazepine, SB-366791 had no effect on either the hyperpolarisation-activated current (I(h)) or Voltage-gated Ca(2+)-channels (VGCC) in cultured rodent sensory neurones. In summary, SB-366791 is a new TRPV1 antagonist with high potency and an improved selectivity profile with respect to other commonly used TRPV1 antagonists. SB-366791 may therefore prove to be a useful tool to further study the biology of TRPV1.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2004

The long-term effect of dietary advice on the diet of men with angina: the diet and angina randomized trial.

INTRODUCTION: The long-term effects on diet of dietary advice to eat fruit and vegetables or fatty fish are not well described. MATERIALS AND METHODS: From 1990 to 1996 3114 men aged 37-70 with treated angina were recruited from general practices in South Wales. A dietitian randomly allocated the eligible men to receive advice to eat more fruit and vegetables, or advice to eat more fatty fish, or both these types of advice or neither. In 2000, a brief self-completion questionnaire was sent to a sample of 1191 of the men known to be alive at the end of March 1999. RESULTS: The questionnaire was returned by 944 of the 1036 men alive at the time the questionnaire was sent. Those given fish advice were consuming more fatty fish but the difference was modest 21.9 g day(-1) vs. 14.0 g day(-1) (P < 0.01). The differences in fruit and vegetables intake between those given fruit advice and those not given fruit advice were small 373.2 g day(-1) vs. 351.7 g day(-1) (P = 0.05). DISCUSSION: Men of this age group may be particularly resistant to fruit and vegetables advice; population-based interventions or interventions targeted at women might be more effective.

Adult↗
PubMed2003

Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency.

BACKGROUND: Faecal urgency and incontinence with rectal hypersensitivity is a distressing, unexplained disorder that is inadequately treated. We aimed to determine whether expression of the heat and capsaicin receptor vanilloid receptor 1 (TRPV1 or VR1) was changed in rectal sensory fibres, and to correlate nerve fibre density with sensory abnormalities. METHODS: We compared full-thickness rectal biopsy samples from nine patients with physiologically characterised rectal hypersensitivity with tissue samples from 12 controls. Sensory thresholds to rectal balloon distension and heating the rectal mucosa were measured before biopsy. We assessed specimens with immunohistochemistry and image analysis using specific antibodies to TRPV1; nerve growth factor (NGF) receptor tyrosine kinase A; glial cell line-derived neurotrophic factor (GDNF); neuropeptides calcitonin gene-related peptide (CGRP) and substance P; the related vanilloid receptor-like protein (VRL) 2; glial markers S-100 and glial fibrillary acid protein (GFAP); and the nerve structural marker peripherin. FINDINGS: In rectal hypersensitivity, nerve fibres immunoreactive to TRPV1 were increased in muscle, submucosal, and mucosal layers: in the mucosal layer, the median% area positive was 0.44 (range 0.30-0.59) in patients who were hypersensitive and 0.11 (0.00-0.21) in controls (p=0.0005). The numbers of peripherin-positive fibres also increased in the mucosal layer (hypersensitive 3.00 [1.80-6.50], controls 1.20 [0.39-2.10]: (p=0.0002). The increase in TRVP1 correlated significantly with the decrease in rectal heat (p=0.03) and the distension (p=0.02) sensory thresholds. The thresholds for heat and distension were also significantly correlated (p=0.0028). Expression of nerve fibres positive for GDNF (p=0.001) and tyrosine kinase A (p=0.002) was also increased, as were cell bodies of the submucosal ganglia immunoreactive to CGRP (p=0.0009). INTERPRETATION: Faecal urgency and rectal hypersensitivity could result from increased numbers of polymodal sensory nerve fibres expressing TRPV1. The triggering factor or factors remain uncertain, but drugs that target nerve terminals that express this receptor, such as topical resiniferatoxin, deserve consideration.

Adult↗
PubMed2003

Observer variability in the Goseki grouping of gastric adenocarcinoma in resection and biopsy specimens.

AIMS: The Goseki grouping of gastric adenocarcinoma has been suggested as a possible prognostic factor. In those centres where it is used, it may be valuable to assess the Goseki grouping of a tumour on the initial diagnostic biopsy as well as on the resection specimen since it may in theory influence management. We examined the robustness of Goseki grouping of gastric adenocarcinoma in representative sections from resection and biopsy specimens in order to assess the consistency of agreement among a group of pathologists. METHODS: A single representative block from 100 gastric resection specimens was studied using a haematoxylin and eosin and mucin (alcian blue/periodic acid-Schiff) stain. These were circulated in batches to members of a group of 12 pathologists who each completed a simple proforma confirming the presence of carcinoma and assigning a Goseki group. In a second circulation the diagnostic biopsy specimen taken prior to resection was examined in the same way. This allowed comparison of the Goseki group of the biopsy and resection specimens. RESULTS: In both studies kappa statistics showed good agreement on tubular differentiation of the carcinoma, but only moderate agreement for the intracellular mucin production, resulting in moderate agreement for the final Goseki group. Correlation between the Goseki group assigned on the biopsy and resected specimens was seen in 62% of the cases. However, the reproducibility was low (kappa 0.375). CONCLUSIONS: The Goseki grouping of resected gastric adenocarcinoma is reproducible and can be used in prognostication. Goseki grouping of biopsy specimens is of limited value in predicting the Goseki group assigned to the resected carcinoma.

Adenocarcinoma↗
PubMed2002

TRPV3 is a temperature-sensitive vanilloid receptor-like protein.

Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin. Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception. This and other experiments--such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons--suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 degrees C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.

Amino Acid Sequence↗
PubMed2002

Leptin regulation of reproductive function and fertility.

Leptin, a 16-KD protein secreted primarily by adipose tissue, was first discovered in the search for a satiety signal. When administered into the brain, leptin depresses appetite. Interestingly, hyperphagic, obese, transgenic mice with leptin deficiency were noted to be reproductively incompetent, and administration of leptin restored their fertility. These pivotal observations led to numerous studies on the site of action of leptin within the hypothalamo-hypophyseal-gonadal axis, and a variety of models have been used ranging from the prepubertal condition to fasting suppression of reproductive hormones. The preponderance of studies thus far has focused on how leptin serves as a metabolic signal of energy balance within the neuroendocrine system, particularly as a regulator of GnRH/LH secretion. Less research has been conducted with other components of the reproductive system, but local effects of leptin have been demonstrated in the gonads where hyperleptinemia suppresses steroidogenesis and potentially affects gamete maturation. This presentation will review the major concepts for the role of leptin in the modulation of fertility and will consider the potential use of leptin in assisted reproductive technology and embryo transfer.

Animals↗
PubMed2002

Inflammatory bowel disease: developing a short disease specific scale to measure health related quality of life.

AIM: To report on the preliminary development of a short scale, the Edinburgh inflammatory bowel disease questionnaire (EIBDQ) to measure disease specific aspects of inflammatory bowel disease (IBD) in terms of both physical impact and health related quality of life (HRQoL) consequences. METHODS: A survey of individuals with Crohn's disease (n=50), ulcerative colitis (n=50) and psoriatic arthritis (n=28) was carried out using the EIBDQ. The data were subject to factor analysis in order to investigate underlying dimension of the EIBDQ which were then analysed for internal consistency. Data for disease specific aspects of the EIBDQ were compared between IBD patients and psoriatic arthritis patients using contingency tables and the underlying dimension of the EIBDQ were correlated with measures of quality of life and psychological morbidity and a disease specific measure. RESULTS: There are three underlying dimensions to the EIBDQ: a disease specific factor, a bowel specific factor and an information factor. The disease specific factor and the bowel specific factor are internally consistent and correlate with other measures of disease activity, quality of life and psychological morbidity. The EIBDQ is able to discriminate between IBD and another inflammatory disease: psoriatic arthritis. CONCLUSION: The EIBDQ is a reliable and valid instrument for measuring disease specific aspects of IBD but further development is required.

Arthritis, Psoriatic↗