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Biomedical subjects

Steve Smith

Publications and source records attributed to Steve Smith.

At least 19 recordsLinked to original sources

Mechanistic characterization of adsorption and slow desorption of phenanthrene aged in soils.

Long-term adsorption of phenanthrene to soils was characterized in a silt-loam (LHS), a sandy soil (SBS), and a podzolized soil (CNS) by use of the Polanyi-Manes model, a Langmuir-type model, and a black carbon-water distribution coefficient (K(BC)) at a relative aqueous concentration (C(e)/S(w)) of 0.002-0.32. Aqueous desorption kinetic tests and temperature-programmed desorption (TPD) were also used to evaluate phenanthrene diffusivities and desorption activation energies. Adsorption contribution in soils was 48-70% after 30 days and 64-95% after 270 days. Significant increases in adsorption capacity with aging suggest that accessibility of phenanthrene to fractions of SBS soil matrix was controlled by sorptive diffusion at narrow meso- and micropore constrictions. Similar trends were not significant for LHS silt-loam or CNS podzol. Analysis of TPD profiles reveal desorption activation energies of 35-53 kJ/mol and diffusivities of 1.6 x 10(-7-)9.7 x 10(-8) cm2/s. TPD tests also indicate that the fraction of phenanthrene mass not diffusing from soils was located within micropores and narrow width mesopores with a corresponding volume of 1.83 x 10(-5-)6.37 x 10(-5) cm3/g. These values were consistent with the modeled adsorption contributions, thus demonstrating the need for such complimentary analytical approach in the risk assessment of organic contaminants.

Adsorption↗

Functional anatomy of interhemispheric cortical connections in the human brain.

Interhemsipheric interaction between the human cerebral hemispheres is served by abundant white-matter fibres in the human corpus callosum (CC). Damage to these fibres has notable behavioural and cognitive sequelae that depend on the exact location of the fibre loss. Until now, correlations between fibre loss and neurological disorders have been limited to post-mortem studies. Here we used probabilistic diffusion magnetic resonance imaging tractography to produce a two-dimensional map of the CC in the mid-sagittal plane. We observed an antero-posterior topography of interhemispheric tracts within the CC, consistent with our current neuroanatomical understanding of post-mortem studies in human. Callosal tract to the left and right hemispheres had comparable volume. Gender, a factor that is often reported to affect CC shape and geometry, also had no effect on the volume of the tracts. Our map showed high consistency across individuals. We propose that this map might be useful in the study of the effects of damage to human CC in neurodegenerative and cognitive disorders.

Adult↗

Effects of trajectory wind direction on ion concentration of PM10.

OBJECTIVE: To study the characterization apportionment of main ion concentrations of PM10 under the influence of trajectory wind direction in London. METHODS: PM10 samples from 1 May 1995 to 30 October 1995 of Oxford Street of Central London were collected, the metals and anions of which were measured using atomic absorption spectrometry (AAS) and ion chromatography (IC). Composite trajectories representative of the air mass arriving in London at the same period were calculated based on basic routine back trajectories from the British Atmospheric Data Centre (BADC). RESULTS: Concentration apportionments of main ions were similar when the trajectory was plotted back at 6 h, 12 h, and 24 h, some were obviously different. Mg, Ba, Pb, and Cu had similar peak apportionments at the area 180 degrees-320 degrees, but Zn and Ni at the area of 90 degrees-270 degrees, NO3 and SO4(2-) at the area of 100 degrees-220 degrees. Cl- concentration peak apportionment was at the area of 220 degrees-300 degrees, which showed that Cl- mainly came from the North Sea. CONCLUSION: Trajectory wind direction has important effect on ion concentration apportionment of PM10 in London. The ions have similar concentration peak apportionments or their correlation coefficients are statistically significant.

Air Pollutants↗

Assessing sequestration of selected polycyclic aromatic hydrocarbons by use of adsorption modeling and temperature-programmed desorption.

Sequestration of phenanthrene and pyrene was investigated in two soils--a sandy soil designated SBS and a silt-loam designated LHS--by combining long-term batch sorption studies with thermal desorption and pyrolysis of amended soil samples. The Polanyi-based adsorption volume and the adsorbed solute mass increased with aging for both soils, thus demonstrating the mechanism for observed sequestration. Despite rigorous thermal analysis, 30-62% (SBS sand) and 8-30% (LHS silt-loam) of phenanthrene could not be recovered after 30-270 days of sorption, with the increase in desorption resistance showing greater significance in SBS sand. For both soils, these values were 20-65% of adsorbed phenanthrene mass. Activation energies estimated from the temperature-programmed desorption (TPD) of sorbed phenanthrene at < or = 375 degrees C were 51-53 kJ/mol, consistent with values derived for desorption of organic compounds from humic materials. The activated first-order model fitting of observed TPD data supports the conclusion that the desorption-resistant fraction of phenanthrene has become sequestered onto condensed organic domains and requires temperatures exceeding 600 degrees C to be released. The work demonstrates the use of thermal analysis in complementing the Polanyi-based adsorption modeling approach for assessing the mechanistic basis for sequestration of organic contaminants in soils.

Adsorption↗

Direct imaging of surface-enhanced Raman scattering in the near field.

By using near-field scanning microscopy/spectroscopy, we show that surface-enhanced Raman scattering (SERS) of rhodamine 6G deposited on self-affine silver colloidal film is localized to small, down to less than 200 nm, portions of the film. The locus of the SERS signals ("hot spots") does not necessarily reside in special topographic elements such as interstices and between nanoparticles. The local SERS enhancement is estimated to be over 3 orders of magnitude higher compared to the far-field measurements. Near-field imaging of SERS directly validates the theory of the optical response of self-affine fractal objects.

Letter↗

Optimal storage conditions for highly dilute DNA samples: a role for trehalose as a preserving agent.

DNA extraction from trace samples or noninvasively collected samples often results in the recovery of low concentration solutions of DNA that are prone to DNA degradation or other loss. Because of the difficulty in obtaining such samples, and their potentially high value in wildlife and forensic studies, it is critical that optimal methods are employed for their long-term storage. We assessed the amplification yield of samples kept under different storage conditions with the addition of potential preserving agents. We stored dilutions of known concentration human placental DNA, and gorilla fecal DNA, under four conditions (+4 degrees C, -20 degrees C, -80 degrees C, dry at room temperature), and with three additives (Tris EDTA (TE) buffer, Hind III digested Lambda DNA, trehalose). The effectiveness of the treatment methods was tested at regular intervals using qPCR to assess the quantity of amplifiable DNA, and a PCR assay of a larger 757 bp fragment to evaluate the quality of that remaining DNA. The highest quantity of DNA remained in samples stored at -80 degrees C, regardless of storage additives, and those dried at room temperature in the presence of trehalose. Surprisingly, DNA quality was best preserved in the presence of trehalose, either dried or at -80 degrees C; significant quality loss occurred with -20 degrees C and +4 degrees C storage.

Animals↗

National survey of palliative care in end-stage renal disease in the UK.

BACKGROUND: Palliative care for patients with end-stage renal disease (ESRD) is a neglected aspect of nephrology. We carried out this survey to establish the current pattern of provision of palliative care for ESRD in the UK. METHODS: An anonymous but numbered questionnaire concerning local palliative care provision was sent to clinical directors of all 69 UK renal units. RESULTS: All the questionnaires were returned. Only 27 (39%) units employ nursing or Professions Allied to Medicine (PAM) staff with palliative care for ESRD patients as a specified part of their role. In 19 of these units, staff spend <4 h per week concerned with palliative care and only five units have staff working for >12 h a week in this role. Fifty-five (80%) units do not have a written protocol for palliative care. Anaemic ESRD patients with an expected survival of >3 months receive blood transfusion in 59 (86%) units, intravenous iron in 61 (88%) units and erythropoietin in 63 (91%) units. Only 37 (54%) units kept a record of patients seen by the unit staff but deemed not suitable for dialysis. CONCLUSION: There is a significant variation in provision of palliative care services across the UK. In some areas, access to palliative care is restricted to patients with malignant disease, and ESRD patients are excluded.

Anemia↗

Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance.

The androgen-signaling pathway is critical to the development and progression of prostate cancer and androgen ablation is a mainstay of therapy for this disease. We performed a genome-wide expression analysis of human prostate cancer during androgen ablation therapy to identify genes regulated by androgen and genes differentially expressed after the development of resistance. Six hundred and fifty-four of 63,175 probe sets detected significant expression changes after 3 months of treatment with goserelin and flutamide. This included 149 genes that were also differentially expressed 36 hours after androgen withdrawal in LNCaP cells. These genes reflect the physiological changes that occur in treated tumors and include potential direct targets of the androgen receptor. Expression profiles of androgen ablation-resistant tumors demonstrated that many of the gene expression changes detected during therapy were no longer present suggesting a reactivation of the androgen response pathway in the absence of exogenous hormone. Therapy resistance was associated with differential expression of a unique set of genes that reflect potential mechanisms of reactivation. Specifically an up-regulation of the androgen receptor and key enzymes for steroid biosynthesis suggest that resistant tumors have increased sensitivity to and endogenous synthesis of androgenic hormones. The specific pathways of reactivation provide opportunities for classification of resistant tumors and targeted therapies.

Algorithms↗

Simulation model of renal replacement therapy: predicting future demand in England.

BACKGROUND: The demand for renal replacement therapy (RRT) in England has risen steadily, although from a lower base than many other developed countries. Predicting the future demand for RRT and the impact of factors such as the acceptance rate, transplant supply and patient survival, is required in order to inform the planning of such services. METHODS: A discrete event simulation model estimates the future demand for RRT in England in 2010 for a range of scenarios. The model uses current prevalence and current and projected future acceptance rates, survival rates and the transitions between modalities to predict future patient numbers. National population and mortality data, published literature and data from the UK Renal Registry and UK Transplant, are used to estimate unmet need for RRT, the impact of changing demography and incidence of Type 2 diabetes, patient haemodialysis (HD) survival and transplant supply. RESULTS: By 2010 the predicted prevalence will have increased from about 30,000 in 2000 to between 42 and 51,000 (900-1000 p.m.p.), an average annual growth of 4.5-6%. Changing transplant supply has a small effect on overall numbers but changes the proportion of patients with functioning graft by up to 8%. Even with an optimistic increase in transplant supply (11% p.a. for 5 years), numbers on HD will continue to rise substantially, especially in the elderly. The factors most influencing future patient numbers are the acceptance rate and dialysis survival. CONCLUSION: This model predicts a substantial growth in the RRT population to 2010 to a rate approaching 1000 p.m.p., particularly in the elderly and those on HD, with a steady state not being reached for at least 25 years.

Adolescent↗

A case of acute hemolysis after ceftriaxone: immune complex mechanism demonstrated by flow cytometry.

An immune complex mechanism for ceftriaxone sodium- induced severe autoimmune hemolytic anemia has previously been demonstrated using routine blood bank techniques. We describe herein a patient with severe hemolysis that subsided once the drug was discontinued. Serologic techniques demonstrated immune complex-mediated ceftriaxone-dependent red cell antibodies. These findings were further supported by the results of flow cytometry, in which a change in basal red cell autofluorescence was seen in the presence of the antibody and the drug. Our case illustrates the adjunctive value of flow cytometry in the diagnosis of ceftriaxone-dependent red cell antibody.

Anemia, Hemolytic, Autoimmune↗

The effects of sequence length and oligonucleotide mismatches on 5' exonuclease assay efficiency.

Although increasingly used for DNA quantification, little is known of the dynamics of the 5' exonuclease assay, particularly in relation to amplicon length and mismatches at oligonucleotide binding sites. In this study we used seven assays targeting the c-myc proto-oncogene to examine the effects of sequence length, and report a marked reduction in efficiency with increasing fragment length. Three of the assays were further tested on 15 mammalian species to gauge the effect of sequence differences on performance. We show that the effects of probe and primer binding site mismatches are complex, with single point mutations often having little effect on assay performance, while multiple mismatches to the probe caused the greatest reduction in efficiency. The usefulness of the assays in predicting rates of 'allelic dropout' and successful polymerase chain reactions (PCRs) in microsatellite genotyping studies is supported, and we demonstrate that the use of a fragment more similar in size to typical microsatellites (190 bp) is no more informative than a shorter (81 bp) fragment. The assays designed for this study can be used directly for quantification of DNA from many mammalian species or, alternatively, information provided here can be used to design unique sequence-specific assays to maximise assay efficiency.

Animals↗

Imaging attentional modulation of pain in the periaqueductal gray in humans.

Pain is an unpleasant sensory and emotional experience usually triggered by stimulation of peripheral nerves and often associated with actual or potential tissue damage. It is well known that pain perception for patients and normal subjects can be modulated by psychological factors, such as attention, stress, and arousal. Our understanding of how this modulation occurs at a neuroanatomical level is poor. Here we neuroanatomically defined a key area in the network of brain regions active in response to pain that is modulated by attention to the painful stimulus. High-resolution functional magnetic resonance imaging was used to define brain activation to painful heat stimulation applied to the hand of nine normal subjects within the periaqueductal gray region. Subjects were asked to either focus on or distract themselves from the painful stimuli, which were cued using colored lights. During the distraction condition, subjects rated the pain intensity as significantly lower compared with when they attended to the stimulus. Activation in the periaqueductal gray was significantly increased during the distraction condition, and the total increase in activation was predictive of changes in perceived intensity. This provides direct evidence supporting the notion that the periaqueductal gray is a site for higher cortical control of pain modulation in humans.

Adult↗

Diffuse axonal and tissue injury in patients with multiple sclerosis with low cerebral lesion load and no disability.

BACKGROUND: Although in situ pathological studies and in vivo magnetic resonance (MR) investigations have shown that axonal injury can be significant in the early stages of multiple sclerosis (MS), diffuse axonal injury is generally considered a secondary event. Cerebral axonal damage can be specifically assessed in vivo by measuring levels of brain N-acetylaspartate (NAA, a specific index of axonal integrity detected by MR spectroscopy). Other new MR measurements such as magnetization transfer ratio (MTr) or computed estimation of brain volume can provide less specific indexes of tissue damage. OBJECTIVE: To determine whether diffuse axonal and tissue injury is present in patients with definite MS who do not show clinically significant disability. METHODS: We measured brain NAA levels (normalized to creatine [Cr]), MTr values, and cerebral volumes in patients with definite MS who had low T2-weighted MR imaging lesion volumes and no clinical disability, and also in age-matched healthy control subjects. RESULTS: Values of central brain NAA/Cr and MTr in normal-appearing white matter were significantly lower in the MS patients than in controls (P<.001). In contrast, total brain volumes were not significantly different between these groups. Similar results were found for MS patients with early disease (duration, <3 years) and with a particularly low cerebral T2-weighted MR imaging lesion load (< or = 2 cm(3)). CONCLUSIONS: Cerebral NAA/Cr and MTr values are diffusely decreased in MS patients with early disease, low demyelinating lesion load, and no significant disability. This suggests that axonal and/or tissue injury begins very early in the course of MS and might be at least partially independent of cerebral demyelination.

Adolescent↗