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Biomedical subjects

Steve Smith

Publications and source records attributed to Steve Smith.

17 recordsLinked to original sources
PubMed2005

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

A method for determining venous contribution to BOLD contrast sensory activation.

While BOLD contrast reflects hemodynamic changes within capillaries serving neural tissue, it also has a venous component. Studies that have determined the relation of large blood vessels to the activation map indicate that veins are the source of the largest response, and the most delayed in time. It would be informative if the location of these large veins could be extracted from the properties of the functional responses, since vessels are not visible in BOLD contrast images. The present study describes a method for investigating whether measures taken from the functional response can reliably predict vein location, or at least be useful in down-weighting the venous contribution to the activation response, and illustrates this method using data from one subject. We combined fMRI at 3 Tesla with high-resolution anatomic imaging and MR venography to test whether the intrinsic properties of activation time courses corresponded to tissue type. Measures were taken from a gamma fit to the functional response. Mean magnitude showed a significant effect of tissue type (p < 0.001) where CSF > veins approximately gray matter > white matter. Mean delays displayed the same ranking across tissue types (p < 0.001), except that veins > gray matter. However, measures for all tissue types were distributed across an overlapping range. A logistic regression model correctly discriminated 72% of the veins from gray matter in the absence of independent information of macroscopic vessels (ROC = 0.72). While tissue classification was not perfect for this subject, weighting the T contrast by the predicted probabilities materially reduced the venous component to the activation map.

Adult↗
PubMed2002

Effectiveness of intra-operative wound infiltration with long-acting local anaesthetic.

BACKGROUND: Postoperative pain relief is of importance to both patients and surgeons. One of the simpler techniques is infiltration of the surgical incision with long acting local anaesthetic. The literature is confusing, with numerous reports attesting to the value of this approach and a similar number disputing the demonstrable benefits. METHODS: A prospective, 'blinded', randomized trial was undertaken involving 18 females undergoing uncomplicated bilateral sapheno-femoral ligation. They received intraoperative bupivacaine infiltration into one or the other of their groin incisions. Postoperatively these patients were asked to assess a number of variables relating to their postoperative pain, each patient thereby acting as their own control. RESULTS: There was no significant difference in the postoperative pain experience between groins infiltrated with bupivacaine and those not infiltrated. Two patients developed wound infections and both of these occurred on the sides which had been infiltrated with bupivacaine, however this was not statistically significant. There was no difference found in pain experience with respect to pre- versus post-incision infiltration. CONCLUSION: Intraoperative wound infiltration with bupivacaine is widely employed as a method of minimizing postoperative pain. This study was unable to demonstrate a benefit of employing the technique in terms of a reduction in the patient's perception of pain. By having each patient act as their own control, we have avoided one of the major deficiencies of previous studies, namely, interpatient variability in assessment and perception of pain.

Adult↗
PubMed2002

Frontal plane knee angle affects dynamic postural control strategy during unilateral stance.

PURPOSE: Center of plantar pressure (COPP) location moves toward the forefoot as ankle plantar flexor muscles attempt to maintain postural control during single leg stance. This study evaluated relationships between frontal plane tibiofemoral joint angulation during relaxed bilateral stance and mean COPP locations during vision-denied single leg stance at 20 degrees knee flexion. METHODS: Fifty-six nonimpaired athletes (29 female, 27 male) were evaluated for frontal plane tibiofemoral joint angulation and standing foot angle by using two-dimensional videography (30 Hz). Mean anterior-posterior and mediolateral COPP locations were assessed during single leg stance on a mat (25 Hz, 15 s). One-way ANOVA and Tukey HSD tests evaluated group differences (P < or = 0.05) based on frontal plane tibiofemoral joint angulation. RESULTS: Group 1 (genu varus or genu valgus < 5 degrees ) displayed a mean anterior-posterior COPP location of 54.2 +/- 6% from the (0,0) coordinate starting point at the anterolateral foot (10.3 +/- 2 cm from the posterior sensor edge). Group 2 (genu varus angulation > or = 5 degrees ) and group 3 subjects (genu valgus angulation > or = 5 degrees ) displayed mean anterior-posterior COPP locations of 60.6 +/- 8% and 60.7 +/- 7% (8.8 +/- 2 cm and 8.7 +/- 2 cm from the posterior sensor edges), respectively. Group 2 (12.5 +/- 3 N x kg(-1)) and group 3 (12.4 +/- 3.1 N x kg(-1)) subjects also displayed greater mean plantar force magnitude/body weight than group 1 (10.3 +/- 2 N x kg(-1)) subjects. Mean ankle plantar flexor moment magnitudes did not differ between groups. CONCLUSIONS: Rearfoot directed mean anterior-posterior COPP locations and greater plantar force magnitudes/body weight suggests that subjects with genu varus or genu valgus relied more on the subtalar and midtarsal joint control function of the ankle plantar flexor muscle group for lower extremity dynamic postural control.

Adolescent↗
PubMed2002

Endoscopic resection of a nasal septal chondrosarcoma: first report of a case.

Advances in endoscopic sinus surgery technique and technology have provided the otolaryngologist with a wide array of surgical options for the management of nasal and paranasal sinus diseases that were once limited to procedures requiring invasive surgery. We describe the case of a patient with a chondrosarcoma of the posterior nasal septum that was resected endoscopically. There have been fewer than 30 reports in the English-language literature of chondrosarcomas arising at this location, and the reported approaches to surgical excision in these case involved craniofacial procedures, facial degloving, facial splitting, and maxillectomy techniques. Until now, no case of endoscopic removal has been reported.

Aged↗
PubMedDate not supplied

Interferon beta-1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: In patients who present with clinically isolated syndromes suggestive of multiple sclerosis, interferon beta-1a is effective in delaying evolution to clinically definite disease and in reducing MRI-measured disease activity. We aimed to assess whether this drug can also reduce the rate of brain volume decrease in such patients enrolled in the ETOMS (early treatment of multiple sclerosis) trial. METHODS: MRI data for brain volume measurements at baseline, month 12, and month 24 were available from 131, 111, and 112 patients assigned treatment (22 microg interferon beta-1a), and 132, 98, and 99 patients assigned placebo respectively. Normalised brain parenchymal volume (NBV) at baseline and percentage brain volume changes (PBVC) were measured with a fully-automated segmentation technique. The primary endpoint was conversion to clinically definite multiple sclerosis due to clinical relapse. Analysis was by intention to treat. FINDINGS: 41 (31%) of 131 patients on interferon beta-1a and 62 (47%) of 132 on placebo converted to clinically definite multiple sclerosis (odds ratio 0.52 [95% CI 0.31-0.86], p=0.0115). Mean PBVC for patients on placebo was -0.83% during the first year, -0.67% during the second year, and -1.68% during the entire study period. Respective values for treated patients were -0.62%, -0.61%, and -1.18%. The changes in brain volume were significant in both groups at all timepoints. A significant treatment effect was detected for month 24 versus baseline values (p=0.0031). The number of new T2 lesions formed during the first year correlated weakly with PBVC during the second year. INTERPRETATION: Early treatment with interferon beta-1a is effective in reducing conversion to clinically definite multiple sclerosis and in slowing progressive loss of brain tissue in patients with clinically isolated syndromes. The modest correlation between new lesion formation and brain volume decrease suggests that inflammatory and neurodegenerative processes are, at least partly, dissociated from the earliest clinical stage of multiple sclerosis onwards.

Adolescent↗
PubMedDate not supplied

What's "unstable" in unstable angina?

The role of emotional distress (e.g., anger, depression, and anxiety) in anginal chest discomfort (ACD) may have been underestimated. The authors review the empirical studies in this area, which are inconsistent with the standard theory on the ischemia-angina relationship; summarize the substantial evidence indicating a strong and consistent cross-sectional/prospective epidemiological association of emotional distress and ischemia/ACD; review the distress-targeted, interventional evidence confirming a causal relationship (i.e., reduced chest discomfort and health system utilization), thus confirming clinical utility of such interventions; and explore the possible mechanisms that might account for the relationship between emotional distress and chest discomfort. Substantial clinical benefit may be achieved by aggressively detecting and treating emotional distress in ACD patients.

Affect↗