Convective warming postbypass reduces postoperative bleeding.
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Blood Coagulation Tests↗
Biomedical subjects
S Edmondson
Publications and source records attributed to S Edmondson.
Rating the appropriateness of coronary angiography, coronary angioplasty and coronary artery bypass grafting: the ACRE study. Appropriateness of Coronary Revascularisation study.
BACKGROUND: Previous studies investigating the appropriateness of invasive management of coronary disease had not reported the internal consistency of their ratings and may now be out of date. The aim of this study was to measure the influence of clinical factors on contemporary ratings of the appropriateness of coronary angiography, percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft (CABG) in the Appropriateness of Coronary Revascularisation (ACRE) study. METHODS: The Delphi-RAND technique was used, in which an expert panel (four cardiologists, three cardiothoracic surgeons, a general physician and a general practitioner), meeting in 1995, rated mutually exclusive indications (n = 2178 for angiography, n = 995 for PTCA and n = 984 for CABG). The main outcome measures were the appropriateness category (inappropriate, uncertain or appropriate) for each of the three procedures and treatment preference. RESULTS: For revascularization, the strongest determinant of inappropriateness was coronary anatomy. The odds ratio (OR) for inappropriate PTCA was 10.6 (95 per cent confidence interval (CI) 4.8-23.5) for the effect of left main stem or three-vessel disease versus single-vessel disease, and for CABG it was 0.06 (95 per cent CI 0.03-0.15). The number of diseased vessels was strongly related to preference for medical, PTCA or CABG treatment (p for linear trend <0.001). Mild versus severe anginal symptoms were associated with inappropriate angiography (OR 2.0 (95 per cent CI 0.9-9.8), although this effect was stronger when only the cardiologists' ratings were considered (OR 10.1 (95 per cent CI 2.4-42.6)). CONCLUSION: These are the first UK ratings of appropriateness covering all three procedures. The associations with clinical factors provide evidence of the internal consistency of these ratings. Prospective validation of these ratings against clinical outcomes is under way in the ACRE study.
Aged↗
Thermodynamic stability of archaeal histones.
The temperature, salt, and pH dependencies of unfolding of four recombinant (r) archaeal histones (rHFoB from the mesophile Methanobacterium formicicum, and rHMfA, rHMfB, and rHPyA1 from the hyperthermophiles Methanothermus fervidus and Pyrococcus strain GB-3a) have been determined by circular dichroism spectroscopy (CD) and differential scanning calorimetry (DSC). The thermal unfolding of these proteins is > 90% reversible, with concentration-dependent apparent Tm values and asymmetric unfolding transitions that are fit well by a two-state unfolding model in which a histone dimer unfolds to two random coil monomers. rHPyA1 dimers are stable in the absence of salt, whereas rHMfA, rHMfB, and rHFoB dimers unfold at 20 degrees C and pH 2 in solutions containing < 200 mM, < 400 mM, and < 1.5 M KCl, respectively. rHMfA, rHMfB, and rHFoB also experience significant cold denaturation in low salt concentrations and at low pH. The midpoint of thermal unfolding of a 1 M protein solution (T degree value) and the temperature dependency of the free energy of unfolding have been established for each histone, and both parameters correlate with the growth temperature of the originating archaeon. The changes in heat capacity upon unfolding are similar for the four histones, indicating that enhanced thermostability is not obtained by altering the curvature of the stability curve. Rather, the stability curves for the histones from the hyperthermophiles are displaced vertically to higher energies and laterally to higher Tmax values relative to the stability curve for rHFoB. The maximal free energies of unfolding for rHFoB, rHMfA, rHMfB, and rHPyA1 are 7.2, 15.5, 14.6, and 17.2 kcal/mol at 32, 35, 40, and 44 degrees C, respectively. T degree values for rHFoB, rHMfA, rHMfB, and rHPyA1 are 75, 104, 113, and 114 degrees C, respectively, at pH 5 in 0.2 M KCl. Structural features within the conserved histone fold that might confer these stability differences are discussed.
Amino Acid Sequence↗
Interferon-resistant human melanoma cells are deficient in ISGF3 components, STAT1, STAT2, and p48-ISGF3gamma.
The mechanism of IFN resistance was examined in three long-term cell lines, SK-MEL-28, SK-MEL-3, and MM96, exhibiting significant variation in responsiveness to the antiproliferative and antiviral effects of type I IFNs. The JAK-STAT components involved in IFN signal transduction were analyzed in detail. After exposure to IFN, activation of the IFN type I receptor-linked tyrosine kinases, JAK-1 and TYK-2, was detected at similar levels in both IFN-sensitive and IFN-resistant cell types, indicating that IFN resistance did not result from a deficiency in signaling at the level of receptor-associated kinase activation. However, analysis of ISGF3 transcription factor components, STAT1, STAT2, and p48-ISGF3gamma, revealed that their expression and activation correlated with cellular IFN responsiveness. The analysis was extended to also include IFN-sensitive primary melanocytes, three additional IFN-resistant melanoma cell lines, and seven cell cultures recently established from melanoma patient biopsies. It was consistently observed that the most marked difference in ISGF3 was a lack of STAT1 in the resistant versus the sensitive cells. Transfection of the IFN-resistant MM96 cell line to express increased levels of STAT1 protein partially restored IFN responsiveness in an antiviral assay. We conclude that a defect in the level of STAT1 and possibly all three ISGF3 components in IFN-resistant human melanoma cells may be a general phenomenon responsible for reduced cellular responsiveness of melanomas to IFNs.
Antineoplastic Agents↗
Coronary artery bypass graft surgery in dialysis patients.
OBJECTIVE: To examine the short term results and long term survival of patients on long term dialysis undergoing coronary artery bypass graft surgery. METHODS: A retrospective analysis of 19 patients on established dialysis who underwent coronary revascularisation between 1983 and 1995; 14 patients (73%) had class IV angina and five (25%) had unstable angina requiring heparin and nitrate infusions before surgery. RESULTS: The 30 day mortality was 5%. Follow up was completed in the remaining 18 patients. The mean follow up time was 34 months (range eight to 61). During the follow up period four patients died of cardiac causes. The actuarial survival at one, two, and three years was 87%, 78%, and 59%, respectively. The overall functional status was significantly improved compared to preoperative levels, with a mean Karnofsky score of 76% (p < 0.01) at three years. CONCLUSIONS: Coronary artery bypass graft surgery can be performed with increased but acceptable morbidity and mortality in chronic dialysis patients. It results in considerable improvement in symptoms and functional status. However, long term survival is limited and this requires further investigation.
Adult↗
Effects of cardioplegia on vascular function and the "no-reflow" phenomenon after ischemia and reperfusion: studies in the isolated blood-perfused rat heart.
The ability of cardioplegia to protect against cardiac contractile dysfunction caused by ischemia and reperfusion is well established. The effects of cardioplegia on vascular injury and the no-reflow phenomenon, however, remain controversial. We used the blood-perfused rat heart to study the effect of St. Thomas' Hospital cardioplegic solution on postischemic endothelium-dependent and endothelium-independent vascular function, the extent of the no-reflow phenomenon, and the temporal relationship between postischemic vascular and contractile function. Isolated rat hearts (16 per group) perfused with blood from a support rat at 60 mm Hg were subjected to 10, 20, 30 or 40 minutes of global ischemia and 40 minutes of reperfusion at 37 degrees C. Eight hearts in each group also received cardioplegia (45 mm Hg for 2 minutes) before ischemia. Left ventricular developed pressure was measured with an intraventricular balloon. At the end of reperfusion, a bolus of 250 micrograms nitro-L-arginine methyl ester was infused to assess endothelium dependent vascular function. After a 20-minute washout, 25 micrograms sodium nitroprusside was infused to assess endothelium-independent vascular function. Fluorescein (1 ml, 1% weight/volume) was then infused to assess no-reflow; this involved freezing the hearts, cutting them into transverse sections (10 x 1 mm), video recording the sections under ultraviolet light, digitizing the images, and analyzing density of fluorescence. No-reflow was defined as a flow of less than 5%. Compared with nonischemic control responses, endothelium-independent vascular function was significantly decreased only after 30 and 40 minutes of ischemia (48.1% +/- 3.8% and 24.3% +/- 7.4%, p < 0.05), but it was significantly protected by cardioplegia (66.6% +/- 3.9% and 64.5% +/- 5.2%, p < 0.05). A significant reduction in endothelium-dependent vascular function was observed after 40 minutes of ischemia (-31.8% +/- 6.6% vs -50.4% +/- 1.6% in control hearts, p < 0.05), and again this was improved by cardioplegia (-45.0% +/- 3.4%, p < 0.05 vs ischemic group). Areas of no reflow were present after 30 and 40 minutes of ischemia (11.9% +/- 6.8% and 33.4% +/- 14.1% of left ventricular mass), and at each time period they were significantly decreased by cardioplegia (0.7% +/- 0.4% and 3.8% +/- 1.6%, p < 0.05). Postischemic contractile dysfunction was observed before any vascular alteration was apparent. After only 20 minutes of ischemia, the postischemic recovery of left ventricular developed pressure fell to 56.7% +/- 4.0%, but both endothelium-dependent vascular function and endothelium-independent vascular function were unaffected. In conclusion, vascular alterations are apparent only after prolonged periods of ischemia, longer than those required to observe contractile dysfunction, and cardioplegia protects against postischemic endothelium-dependent and endothelium-independent vascular dysfunction and reduces the extent of the no-reflow phenomenon.
Animals↗
Error analysis of macromolecular structures determined with nuclear magnetic resonance data.
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Amino Acid Sequence↗
Defining the precision with which a protein structure is determined by NMR. Application to motilin.
A simple procedure is introduced for accurately defining the precision with which the Cartesian coordinates of any macromolecular structure are determined by nuclear Overhauser data. The method utilizes an ensemble of structures obtained from an array of independent simulated data sets derived from a final structure. Using the noise-free, back-calculated NOE spectrum as the "true" NOE spectrum, simulated Monte Carlo data sets are created by superimposing onto the "true" spectrum Gaussian distributed noise with a standard deviation equal to that of the residuals. Full relaxation matrix refinements of the simulated data sets provide probability distributions of the Cartesian coordinates for each atom in the model. Molecular dynamics simulations are included to estimate the effect of sparse information on the precision. The procedure is applied here to the 22-residue peptide hormone motilin, and the results are compared to those obtained using the conventional method of analyzing multiple refinements using a single distance constraint set. The average root mean square deviation for alpha-carbon atoms in the central portion (Arg12-Arg18) of the single helix of motilin was determined to be 0.72 A by the Monte Carlo method, compared to 1.3 A determined by an analysis of the 10 best DIANA structures using the same number of constraints between the same atoms. The origin of the bias of the conventional method is discussed.
Amino Acid Sequence↗
The solution structure of motilin from NMR distance constraints, distance geometry, molecular dynamics, and an iterative full relaxation matrix refinement.
A model of the structure of the 22 amino acid residue gastrointestinal peptide hormone motilin in 30% hexafluoro-2-propanol has been obtained by using distance constraints obtained from two-dimensional nuclear Overhauser enhancements. A set of initial structures have been generated by using the distance geometry program DIANA, and 10 of these structures have been refined by using restrained molecular dynamics (AMBER). The resulting structures are virtually indistinguishable in terms of constraint violations and energies and display less than 0.5-A root mean square deviations (RMSD) of the backbone atom positions from Tyr7 to Lys20. A comparison of back-calculated and experimental NOE intensities indicates that RMSD's are not the best indicators of the goodness of fit or of the precision with which the structure is defined. The structure was further refined by fitting the experimental NOE data using an iterative full relaxation matrix analysis. The mean error between the observed and calculated backbone NOE intensities for the final refined structure was 0.23 for the full length of the molecule, 0.18 for the region from Glu9 to Lys20, and 0.29 for the region from Phe1 to Gly8. R factors for the same regions were 0.27, 0.19, and 0.43, respectively. All of the NOE-determined structures consistently display an alpha-helix which extends from Glu9 to Lys20. Considerable lack of definition of structure exists at the amino and carboxyl ends of the molecule and also in the vicinity of Thr6-Tyr7-Gly8. A tendency to form a wide turn appears to exist over the sequence Pro3-Ile4-Phe5-Thr6, but the structure in this region is not well defined by the NOE data.
Amino Acid Sequence↗
Iatrogenic hypocalcemic tetany.
The treatment of a patient with hypocalcemic tetany secondary to sodium phosphate enemas is reported. The patient presented with a serum calcium level of 5.2 mg/dL and a phosphate level of 17.5 mg/dL. Physical manifestations included tetanic contraction of the muscles of the legs and arms. There was rapid symptomatic resolution with IV calcium. The electrolyte imbalance normalized over the next two days with oral calcium supplementation.
Calcium Gluconate↗
Mechanisms of asbestos-induced squamous metaplasia in tracheobronchial epithelial cells.
Within 1 to 4 weeks after exposure to asbestos, differentiated rodent and human tracheobronchial epithelial cells in organ culture undergo squamous metaplasia, a putative preneoplastic lesion characterized by conversion of mucociliary cell types to keratinizing cells. The exogenous addition of retinal acetate (RA) to culture medium of hamster tracheal organ cultures reverses preestablished, asbestos-induced squamous metaplasia, although data suggest that the effectiveness of RA decreases as the length of time between exposure to asbestos and initial application of RA increases. alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), inhibits squamous metaplasia caused by asbestos or vitamin A deficiency, whereas addition of methylglyoxal bis(guanylhydrazone) (MGBG), a structural analog of spermidine and inhibitor of S-adenosylmethionine decarboxylase, causes an enhancement of metaplasia under both circumstances. Basal cell hyperplasia and increased incorporation of 3H-thymidine by tracheal epithelial cells also are seen after addition of the polyamines, putrescine or spermidine, to tracheal organ cultures, an observation supporting the importance of polyamines in the development of this lesion. The use of retinoids and inhibitors of ODC could be promising as preventive and/or therapeutic approaches for individuals at high risk for development of asbestos-associated diseases.
Animals↗
Cryoablation of the accessory pathway in Wolff-Parkinson-White syndrome: initial results and long term follow up.
Cryoablation of the accessory pathway was used in the management of 20 patients with pre-excitation syndromes. All patients had presented with paroxysmal atrioventricular reentrant tachycardia; in addition, six had experienced atrial fibrillation. In 16 patients pre-excitation was overt and in four the accessory pathway was concealed. Intraoperative epicardial and endocardial mapping showed 10 left free wall pathways, seven septal pathways, and four right free wall pathways. One patient had two right free wall accessory pathways. There was one postoperative death (from a ruptured cerebral haemangioma) and one patient had transient hemiparesis. There was early recurrence of arrhythmia or pre-excitation in six patients and five of these were among the first ten in the series. Four of the six underwent successful reoperation; 17 patients remain symptom free of all antiarrhythmic treatment. Two patients did not undergo reoperation--one became symptom free on drugs that had previously been ineffective and the other received an antitachycardia pacemaker. The mean period of follow up was six years. Accessory pathway function was not restored and atrioventricular nodal function was preserved in all patients, demonstrating the feasibility of this technique in the long term management of patients with the pre-excitation syndrome.
Adult↗
Labetalol: false-positive indices by EMIT-d.a.u. assay and Toxi-Lab A urine screen.
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Cross Reactions↗
Collagen content of atherosclerotic arteries is higher in smokers than in non-smokers.
The biochemical composition of coronary endarterectomy and aortic samples obtained during 52 coronary artery bypass graft operations was analysed. The content of cholesterol or collagen relative to protein in the aorta or endarterectomy specimens did not correlate with serum total cholesterol, triglyceride, or high-density-lipoprotein cholesterol, nor were there any significant differences between samples from normotensive and hypertensive patients. However, smokers had a significantly higher content of collagen in coronary endarterectomy specimens and the aorta and a higher content of cholesterol in the aorta than non-smokers.
Aorta↗
Circular dichroism and fluorescence-detected circular dichroism of deoxyribonucleic acid and poly[d(A-C).d(G-T)] in ethanolic solutions: a new method for estimating circular intensity differential scattering.
A method is presented for determining the circular dichroism (CD) of systems whose CD spectra contain contributions from CD differential scattering. The technique is shown to detect light over 4 pi steradians, and thus, for the first time, a complete correction for scattering is possible. The method is applied to ethanol-condensed DNA and poly[d(A-C).d(G-T)]. From the results obtained, the former are proposed to have an A-type secondary structure. The condensed polynucleotide particles are shown to exhibit behavior similar to that of cholesteric liquid crystals. CD difference spectra, obtained from the scattering corrections and showing the contributions to different sections of the scattering envelope, are displayed. It is asserted that these scattering patterns contain information about the tertiary structure of the condensed DNA particles studied.
1-Naphthylamine↗
Comparison of techniques improving the resolution of standard Coulter cell sizing systems.
Latex spheres with nominal diameters of 1.857, 2.02, 3.5, 5.2 and 9.69 mum were used to compare improvement in Coulter resolution gained (a) by a simple hydrodynamic focusing modification and (b) by Coulter edit and high resolution circuits. Since pulse size profiles of focused 9.69-mum spheres appeared quasimonodisperse [geometric SD (GSD) congruent to 0.016 congruent to (1 + Arithmetic SD/arithmetic mean)], unfocused profiles of these particles approximated the error function resulting from inhomogeneities in the electric and hydrodynamic sensing-zone fields. As expected, this field error function differed systematically with differences in orifice diameters (30, 50, 70 and 100 mum) and length to diameter ratios (0.75 or 1.2), the error being reduced slightly by the edit circuit and considerably by the high resolution circuit. Data on the 1.857- and 2.02-mum spheres (focused GSDs congruent to 1.06) and 3.5- and 5.2-mum spheres (focused GSDs congruent to 1.6) indicated that the field error affected closely similar particles similarly but its influence on the unfocused population means and variances differed in the GSD regions of 1.06 and 1.60.
Autoanalysis↗