Biomedical subjects
C Evans
Publications and source records attributed to C Evans.
Comparison of the humoral markers of bone turnover and bone mineral density in patients on haemodialysis and continuous ambulatory peritoneal dialysis.
Renal osteodystrophy is an important complication in patients with end-stage renal disease on maintenance dialysis. The aim of this study was to compare the biochemical markers of bone formation (serum collagen type I C-terminal propeptide) and resorption (serum deoxypyridinoline - DPD - and pyridinoline - PYR) with the bone mineral density (BMD) at lumbar spine, femoral neck, and forearm in patients with end-stage renal disease on haemodialysis (HD) versus continuous ambulatory peritoneal dialysis (CAPD). Fifty-nine adult patients, 45 on CAPD (18 females, 27 males) and 14 on HD (2 females, 12 males), were studied. The mean age was 44 +/- SEM 1.6 and 54.4 +/- 4.8 years, respectively. No significant differences in serum calcium, phosphorus, creatinine, and parathyroid hormone were found between patients on HD and CAPD in predialysis samples. Serum urea was significantly lower (p = 0.02) in the CAPD group. Serum PYR (nmol/l) and DPD (nmol/l) were significantly higher in patients on HD as compared with those on CAPD: 105 +/- 23.3 versus 43.7 +/- 3.47 (p = 0.007) and 31.0 +/- 2.4 versus 24.4 +/- 1.4 (p = 0.027), respectively. The results were still significantly higher in the HD patients following correction for serum creatinine and body mass index. There was a close correlation between dialysate DPD and creatinine in both dialysis modalities (HD r = 0.9, CAPD r = 0.76). The clearance of DPD did not differ significantly between the CAPD membrane and the HD membrane (p = 0.22). Serum collagen type I C-terminal propeptide was not significantly different between the HD and CAPD patients. The results were unaffected following correction for age and gender. The BMD was measured in 38 (65%) of the patients (HD n = 8, CAPD n = 30) by dual-energy X-ray absorptiometry and expressed as 'Z' scores. This was reduced at all sites in the patients with end-stage renal disease. The BMD was significantly lower at the ultradistal forearm (mostly trabecular bone) in HD patients as compared with CAPD patients (n = 0.02). A similar trend was observed at the lumbar spine, although the results failed to reach significance. In the whole population (n = 38), linear regression analysis revealed a significant negative correlation between BMD at the ultradistal forearm and serum PYR (r = -0.35, p = 0.04) and DPD (r = -0.33, p = 0.049). Combined measurements of BMD and biochemical markers of bone resorption may have potential in the identification of patients at high risk of bone loss who may require further evaluation of bone remodeling by bone histomorphometry.
Service profiling and outcomes benchmarking using the CORE-OM: toward practice-based evidence in the psychological therapies. Clinical Outcomes in Routine Evaluation-Outcome Measures.
To complement the evidence-based practice paradigm, the authors argued for a core outcome measure to provide practice-based evidence for the psychological therapies. Utility requires instruments that are acceptable scientifically, as well as to service users, and a coordinated implementation of the measure at a national level. The development of the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) is summarized. Data are presented across 39 secondary-care services (n = 2,710) and within an intensively evaluated single service (n = 1,455). Results suggest that the CORE-OM is a valid and reliable measure for multiple settings and is acceptable to users and clinicians as well as policy makers. Baseline data levels of patient presenting problem severity, including risk, are reported in addition to outcome benchmarks that use the concept of reliable and clinically significant change. Basic quality improvement in outcomes for a single service is considered.
A luminescent bioassay for thyroid blocking antibodies.
OBJECTIVE: Thyroid blocking antibodies (TBAb) have a role in the development of hypothyroidism and in the neonate are responsible for transient hypothyroidism. Specific measurement of TBAb requires a bioassay, but current methods are lengthy and cumbersome. We describe a rapid luciferase-based method for the detection of TBAb using the lulu* cell line which is suitable for the provision of a clinical service PATIENTS AND MEASUREMENTS: Chinese hamster ovary (CHO) cells were transfected with human TSH-R together with G418 resistance and a cAMP responsive luciferase construct. Stable pools of transfected cells were selected and clones identified by limiting dilution. Clone lulu* gave the best response to stimulation by TSH and was used to develop a bioassay for TBAb. The luminescent bioassay conditions have been optimized and validated using 12 serum samples from patients found to be TBAb positive in a bioassay using an established method quantifying cAMP by radioimmunoassay (RIA). The effect of thyroid stimulating antibodies (TSAb) on the calculation of Inhibition Index (InI) using two previously described formulae have been investigated and we have used serum containing both TSAb and TBAb to investigate detection of TBAb in samples containing more than one type of activity. RESULTS: Lulu* displays a dose dependent increase in luciferase expression in response to stimulation with bovine (b) TSH which is more effective in serum free medium than in salt free buffer. TSH stimulated luciferase expression can be inhibited by TBAb in either serum or an immunoglobulin preparation. Using optimized assay conditions, challenging 10% serum against 1 U/l bTSH in culture medium, we have tested 31 euthyroid sera to determine a reference range: InI values >23% were considered positive. Twelve samples previously shown to contain TBAb by an established method quantifying cAMP by RIA were positive by the luciferase-based assay. Of control sera, 20/20 systemic lupus erythematosus, 13/14 rheumatoid arthritis, 12/12 multinodular goitre were negative. We demonstrated that if more complex formulae are used to calculate InI, false positive TBAb results can be obtained in samples containing only TSAb. Finally, when sera contain both TSAb and TBAb, the net activity of stimulating and blocking antibodies is detected in the bioassay. Where TSAb are also present, analysis of serum may be required at several dilutions to detect TBAb. CONCLUSIONS: We describe the production of a new cell line, lulu*, and its use to develop a luminescent bioassay for TBAb suitable for clinical use. Comparing two established methods of calculating TBAb, we found that they do not give identical results. In light of this, the high prevalence reported for TBAb in some studies has to be considered with caution.
Uroradiology: imaging in prostate cancer.
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Synaptic and neurotransmitter activation of cardiac vagal neurons in the nucleus ambiguus.
Cardiac vagal neurons play a critical role in the control of heart rate and cardiac function. These neurons, which are primarily located in the nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DMNX), dominate the neural control of heart rate under normal conditions. Cardiac vagal activity is diminished and unresponsive in many disease states, while restoration of parasympathetic activity to the heart lessens ischemia and arrhythmias and decreases the risk of sudden death. Recent work has demonstrated that cardiac vagal neurons are intrinsically silent and therefore rely on synaptic input to control their firing. To date, three major synaptic inputs to cardiac vagal neurons have been identified. Stimulation of the nucleus tractus solitarius evokes a glutamatergic pathway that activates both NMDA and non-NMDA glutamatergic postsynaptic currents in cardiac vagal neurons. Acetylcholine excites cardiac vagal neurons via three mechanisms, activating a direct ligand-gated postsynaptic nicotinic receptor, enhancing postsynaptic non-NMDA currents, and presynaptically by facilitating transmitter release. This enhancement by nicotine is dependent upon activation of pre- and postsynaptic P-type voltage-gated calcium channels. Additionally, there is a GABAergic innervation of cardiac vagal neurons. The transsynaptic pseudorabies virus that expresses GFP (PRV-GFP) has been used to identify, for subsequent electrophysiologic study, neurons that project to cardiac vagal neurons. Bartha PRV-GFP-labeled neurons retain their normal electrophysiological properties, and the labeled baroreflex pathways that control heart rate are unaltered by the virus.
Presymptomatic testing in myotonic dystrophy: genetic counselling approaches.
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A randomized controlled trial assessing the health economics of realtime teledermatology compared with conventional care: an urban versus rural perspective.
A randomized controlled trial was carried out to measure the cost-effectiveness of realtime teledermatology compared with conventional outpatient dermatology care for patients from urban and rural areas. One urban and one rural health centre were linked to a regional hospital in Northern Ireland by ISDN at 128 kbit/s. Over two years, 274 patients required a hospital outpatient dermatology referral--126 patients (46%) were randomized to a telemedicine consultation and 148 (54%) to a conventional hospital outpatient consultation. Of those seen by telemedicine, 61% were registered with an urban practice, compared with 71% of those seen conventionally. The clinical outcomes of the two types of consultation were similar--almost half the patients were managed after a single consultation with the dermatologist. The observed marginal cost per patient of the initial realtime teledermatology consultation was 52.85 Pounds for those in urban areas and 59.93 Pounds per patient for those from rural areas. The observed marginal cost of the initial conventional consultation was 47.13 Pounds for urban patients and 48.77 Pounds for rural patients. The total observed costs of teledermatology were higher than the costs of conventional care in both urban and rural areas, mainly because of the fixed equipment costs. Sensitivity analysis using a real-world scenario showed that in urban areas the average costs of the telemedicine and conventional consultations were about equal, while in rural areas the average cost of the telemedicine consultation was less than that of the conventional consultation.
Renal arteriography using gadolinium enhanced 3D MR angiography--clinical experience with the technique, its limitations and pitfalls.
Gadolinium enhanced 3D MR angiography (MRA) is becoming a widely accepted technique for imaging the vascular system. We set out to evaluate its accuracy and reliability in visualization of renal arteries in the clinical setting. Gadolinium enhanced MRA was performed in 15 potential live renal donors and 26 patients suspected of having renal artery stenosis who were referred for digital subtraction angiography (DSA). MRA was performed on a 1.5 T MR scanner in a single breath hold. Images from each study were prospectively analysed for demonstration of number of main and accessory renal arteries and degree of renal artery stenosis in a double blind fashion. All the main and accessory arteries were visualized on MRA in the renal donor group, but in one case a branch was not identified owing to breathing artefact. In one case, an extrarenal vascular anomaly was not demonstrated on MRA. In the renal artery stenosis group, sensitivity, specificity and negative predictive values of 96%, 93% and 96% were obtained for clinically significant stenosis (>50%). Gadolinium enhanced MRA proved to be a useful technique in demonstration of renal arterial anatomy and grading of renal artery stenosis. However, we encountered some pitfalls and limitations of the technique during the process. It is important to be aware of these before accepting it as the sole technique in clinical practice.
Dietary fatty acids influence the production of Th1- but not Th2-type cytokines.
C57B16 mice were fed for 6 weeks on a low-fat diet or on high-fat diets containing coconut oil (rich in saturated fatty acids), safflower oil [rich in n-6 polyunsaturated fatty acids (PUFAs)], or fish oil (rich in n-3 PUFAs) as the main fat sources. The fatty acid composition of the spleen lymphocytes was influenced by that of the diet fed. Thymidine incorporation into concanavalin A-stimulated spleen lymphocytes and interleukin (IL)-2 production were highest after feeding the coconut oil diet. Interferon (IFN)-gamma production was decreased by safflower oil or fish oil feeding. IL-4 production was not significantly affected by diet, although production was lowest by lymphocytes from fish oil-fed mice. The ratio of production of Th1- to Th2-type cytokines (determined as the IFN-gamma/IL-4 ratio) was lower for lymphocytes from mice fed the safflower oil or fish oil diets. After 4 h of culture, IL-2 mRNA levels were higher in cells from mice fed coconut oil, and IFN-gamma mRNA levels were higher in cells from mice fed coconut oil or safflower oil. After 8 h of culture, IL-2, IFN-gamma, and IL-4 mRNA levels were lowest in cells from mice fed fish oil. The ratio of the relative levels of IFN-gamma mRNA to IL-4 mRNA was highest in cells from mice fed coconut oil and was lowest in cells of mice fed fish oil. The influence of individual fatty acids on IL-2 production by murine spleen lymphocytes was examined in vitro. Although all fatty acids decreased IL-2 production in a concentration-dependent manner, saturated fatty acids were the least potent and n-3 PUFAs the most potent inhibitors, with n-6 PUFAs falling in between in terms of potency. It is concluded that saturated fatty acids have minimal effects on cytokine production. In contrast, PUFAs act to inhibit production of Th1-type cytokines with little effect on Th2-type cytokines; n-3 PUFAs are particularly potent. The effects of fatty acids on cytokine production appear to be exerted at the level of gene expression.
The effects of solo singing, choral singing and swimming on mood and physiological indices.
The effects of solo singing, choral singing and swimming on mood and physiological indices were compared. Engaging in these activities reduced tense arousal and increased energetic arousal, positive hedonic tone and heart rate. Effects were greater for swimming than for singing, with little difference between choral and solo singing. Possible mechanisms and the implications for mental well-being are discussed.
Surface modification using a commercial triple quadrupole mass spectrometer.
We report instrumental modifications to a commercial mass spectrometer that allow surface modification experiments to be performed using low-energy (electronvolt range) mass-selected ion beams. The design of the detector housing allows placement of the surface on the ion optical axis and some distance beyond the off-axis detector. Manipulation of the potentials applied to the final lens, detector housing, conversion dynode, and electron multiplier allow the ions to pass through the detector housing and impinge upon the surface without loss of the normal mode of detector operation. Ex situ analysis of the modified surface is performed using a home-built multisector mass spectrometer. The ability to modify organic thin films is demonstrated by a number of soft landing and surface modification experiments including (i) soft landing of (CH3)2SiNCS+ ions formed from trimethylsilyl isothiocyanate upon a fluorinated self-assembled monolayer (F-SAM) surface, (ii) soft landing and dissociative soft landing of the pseudomolecular cation of triphenylpyrylium tetrafluoroborate, viz. the triphenylpyrylium cation, upon an F-SAM surface, (iii) dissociative soft landing of 35ClCH2(CH3)2SiOSi(CH3)2+ formed from 1,3-bis(chloromethyl)disiloxane upon an F-SAM surface, (iv) surface passivation by reaction of the trimethylsilyl cation, Si(CH3)3+, with a hydroxyl-terminated self-assembled monolayer (OH-SAM), and (v) transhalogenation by reaction of CCl3+ (m/z 119) with an F-SAM surface.
Baseline HIV type 1 genotypic resistance to a newly added nucleoside analog is predictive of virologic failure of the new therapy.
We evaluated the predictive value of baseline HIV-1 genotypic resistance mutations for failure of a nucleoside reverse transcriptase inhibitor (NRTI) containing therapy. The change in therapy of 88 HIV-1-infected patients was analyzed retrospectively, relating the genotypic resistance profile at baseline to the evolution of viral load and CD4+ T cell counts. Genotypic resistance at baseline and at 6 months was evaluated with the LiPA HIV-1 RT, which detects mutations at codons 41, 69, 70, 74, 184, and 215. At 1 to 3 months after change in therapy, patients without preexisting resistance mutations to the new drug (group S) had a significantly better evolution in viral load (reduction of 0.37 log(10)) compared with patients with known preexisting resistance mutation(s) (group R) (increase of 0.08 log(10)). This difference was particularly striking for patients with the baseline M184V mutation and whose treatment was modified by the addition of lamivudine. After 6 months the median difference in viral load evolution between the two groups increased to 0.61 log(10): the viral load of patients of group S was still 0.18 log(10) below baseline while patients of group R had an increase of 0.43 log(10) in viral load above baseline. Changes in CD4+ T cell counts were not significantly different. The evolution in viral load in HIV-1-infected patients with and without baseline resistance mutation(s) toward a newly added NRTI is significantly different at 1-3 months and at 6 months after changing or adding one NRTI.
"I don't like Mondays"-day of the week of coronary heart disease deaths in Scotland: study of routinely collected data.
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[Cytokine-induced nitric oxide production of joint cartilage cells in continuous passive movement. Anti-inflammatory effect of continuous passive movement on chondrocytes: in vitro study].
PURPOSE: The temporomandibular joint is a place of motion where release of proinflammatory cytokines like interleukin-1 beta (IL-1 beta) induces cartilage destruction via production of nitric oxide (NO). The purpose of this study was to evaluate the effects of continuous passive motion in the form of cyclic stretch on the synthesis of inducible nitric oxide synthase (iNOS). METHODS: Articular chondrocytes were harvested from rabbit cartilage slices and cultured in F12 medium supplemented with 10% fetal calf serum. Subsequently, cells (10(5)/ml per well) were transferred to Flexercell plates, grown to 90% confluency, and subjected to one of the following regimens: (1) no mechanical strain (10 Hz, 20% elongation rate); (2) rhIL-1 beta (1 ng/ml); (3) mechanical strain; (4) mechanical strain and rhIL-1 beta. The cells were exposed to cyclic stretch for 24 h. Thereafter, cells were trypsinized and centrifuged on microscope slides in a cytospin centrifuge. The presence of iNOS was determined by indirect immunoperoxidase staining using polyclonal rabbit anti-iNOS as primary antibodies, and goat anti-rabbit IgG conjugated with horseradish peroxidase (HRP) as secondary antibodies. Diaminobenzidine was used as substrate for HRP. Total NO production was spectrophotometrically measured in the supernatants of cultures using Greiss reaction. All experiments were done in triplicates and the statistical significance was analyzed by Student's t-test. RESULTS: Cells with treatment 1 and 3 did not exhibit presence of iNOS. IL-1 beta-treated cells in group 2 exhibited intense peroxidase staining. Cells in group 4 exposed to IL-1 and mechanical stress showed staining with considerably less intensity. Control cells treated with normal rabbit IgG as a primary antibody did not exhibit peroxidase staining. The data were further confirmed by measurement of statistically significant differences of NO levels in supernatants assessed in the four different treatment groups. CONCLUSION: Our findings suggest that continuous passive motion exerts anti-inflammatory effects on chondrocytes, downregulating the quantity of iNOS-positive cells. Since NO acts as an intracellular, transcellular, and cytotoxic molecule, it has a basic importance for proper post-traumatic and postoperative TMJ function as well as the course and therapy of inflammatory TMJ diseases.
Etorphine increases the number of mu-opioid receptor-positive cells in the cerebral cortex.
Imunocytochemical techniques were used to determine whether agonist-induced activation of mu-opioid receptors alters the number and distribution of mu-opioid receptor-positive cells in the rat cerebral cortex. In untreated rats, mu-opioid receptor immunoreactivity was localized to neuronal perikarya and dendrites and to neuropilar punctate structures. mu-Opioid receptor-positive neurons were mostly in layers II and III and exhibited a bipolar or bitufted morphology. In rats treated with the mu-opioid receptor agonist etorphine (0.1mg/kg intraperitoneally) and perfused after different survival periods, there was an enhancement of immunostaining for mu-opioid receptors observed at 15min, reaching a maximum at 60min, and which returned to normal at 480min. Etorphine-induced effects included an increase in the intensity of cellular and neuropil staining; statistical analysis showed that the number of mu-opioid receptor-positive cells in etorphine-treated groups was significantly higher than in controls or saline-treated rats. In animals that received both etorphine and the mu-opioid receptor antagonist naloxone, the pattern of mu-opioid receptors immunoreactivity was similar to that of untreated animals. This study shows that the number of mu-opioid receptor-positive cells is significantly increased following etorphine treatment and suggests that agonist treatment may be exploited to increased immunostaining of mu-opioid receptors and also of other G-protein coupled receptors.
Potential of gene therapy for treating osteogenesis imperfecta.
Osteogenesis imperfecta is a heterogeneous group of genetic disorders that affect connective tissue integrity, with bone fragility being the major clinical feature. Most forms of osteogenesis imperfecta are the result of mutations in the genes that encode the pro alpha1 and pro alpha2 polypeptide chains of Type I collagen. Because osteogenesis imperfecta is an incurable genetic disease, cell therapy and gene therapy are being investigated as potential treatments. Gene therapy for osteogenesis imperfecta however is a major challenge; because most of the mutations in osteogenesis imperfecta are dominant negative, supplying the normal gene without silencing the abnormal gene may not be beneficial. Null mutations in which an allele is not expressed or absent may be amenable to gene therapy or alternatively after silencing a mutant allele, a normal gene could be supplied. In addition, overexpression of the normal collagen gene in cells expressing mutant collagen polypeptide chains potentially could lead to synthesis of a sufficient percentage of normal molecules to normalize clinical status. The authors currently are examining the possibility of developing gene therapy for treating a mouse model of human osteogenesis imperfecta (oim) using bone marrow stromal cells as vehicles for delivering normal collagen genes to bone. In the current study, the potential of gene therapy for treating osteogenesis imperfecta is discussed in the context of the complexity of the mutations in Type I collagen genes that lead to different osteogenesis imperfecta phenotypes.
Actinic keratosis: time to call a spade a spade.
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