PubMed Health⌕ Search

Biomedical subjects

F Heatley

Publications and source records attributed to F Heatley.

14 recordsLinked to original sources
PubMed2001

The cost-effectiveness of magnetic resonance imaging for investigation of the knee joint.

OBJECTIVES: This study considered the role of magnetic resonance imaging (MRI) in the diagnosis of knee injuries in a district general hospital (DGH) setting. The principal objective was to identify whether the use of MRI had a major impact on the clinical management of patients presenting with chronic knee problems, in whom surgery was being considered, whether it reduced overall costs and whether it improved patient outcome. In addition, the research: (1) explored the 'diagnostic accuracy' of initial clinical investigation of the knee by an orthopaedic trainee, consultant knee specialist and consultant radiologist; (2) considered the variability and diagnostic accuracy of interpretations of knee MRI investigations between radiologists; (3) measured the strength of preference for the potential diagnostic/therapeutic impact of knee MRI (i.e. the avoidance of surgery). METHODS - RANDOMISED CONTROLLED TRIAL: The research was based on a single-centre randomised controlled trial conducted at Kent and Canterbury Hospital. Patients attending with knee problems in whom surgery was being considered were recruited from routine orthopaedic clinics. Most patients had been referred by their general practitioner. Patients were randomised to either investigation using an MRI scan (MRI trial arm) or investigation using arthroscopy (no-MRI trial arm). The study investigated the benefits of knee MRI at two levels: diagnostic/therapeutic impact (i.e. avoidance of surgery) and patient outcome (using the Short Form with 36 items and EQ-5D quality-of-life measurement instruments). Quality of life was assessed at baseline and at 6 and 12 months. Costs were assessed from the perspectives of the NHS and patients. All analyses were by intention to treat. METHODS - SUBSTUDIES (INVESTIGATION OF DIAGNOSTIC ACCURACY): For the investigation of diagnostic accuracy of initial clinical investigation, the sample comprised 114 patients recruited in a separate study conducted at St Thomas' Hospital. The sample was drawn from patients presenting at the Accident and Emergency Department with an acute knee injury. All study patients received an MRI scan, but initial diagnosis was made without access to the scan or the radiologist's report. After 12 months, all clinical notes and MRI scans of study patients were reviewed and a final 'reference standard' diagnosis for each patient was reached. Comparison was made between the diagnosis recorded by each clinician (i.e. orthopaedic trainee, knee specialist and consultant radiologist) and the reference diagnosis. METHODS - SUBSTUDIES (INVESTIGATION OF THE GENERALISABILITY OF RESULTS): For this substudy, the MRI images from 80 patients (recruited at St Thomas' Hospital) were interpreted independently by seven consultant radiologists at DGHs and the St Thomas' Hospital MRI radiologist. For each area of the knee, the level of agreement (measured using weighted kappa) between the responses of the eight radiologists and the reference standard diagnosis was assessed. METHODS - SUBSTUDIES (INVESTIGATION OF PREFERENCES): The investigation of potential patient preferences for the diagnostic/therapeutic impact of MRI was explored using a discrete choice conjoint measurement research design. Choices involved selecting between two alternative scenarios described using four attributes, and data were collected from 585 undergraduate sports science students and analysed using a random-effects probit model. RESULTS - RANDOMISED CONTROLLED TRIAL: The trial recruited 118 patients (59 randomly allocated to each arm). The two groups were similar in important respects at baseline. The central finding was of no statistically significant differences between groups in all measures of health outcome, although a trend in favour of the no-MRI group was observed. However, the use of MRI was found to be associated with a positive diagnostic/therapeutic impact: a significantly smaller proportion of patients in the MRI group underwent surgery (MRI = 0.41, no-MRI = 0.71; p = 0.001). There was a similar mean overall NHS cost for both groups. RESULTS - SUBSTUDIES (INVESTIGATION OF DIAGNOSTIC ACCURACY): The exploration of diagnostic accuracy found that, when compared to orthopaedic trainees (44% correct diagnoses) or to radiologists reporting an MRI scan (68% correct diagnoses), the accuracy rate was higher for knee specialists (72% correct diagnoses). RESULTS - SUBSTUDIES (INVESTIGATION OF THE GENERALISABILITY OF RESULTS): This generalisability study indicated that, in general terms, radiologists in DGHs provide accurate interpretations of knee MRI images that are similar to a radiologist at a specialist centre. The one area of the knee for which this did not hold was the lateral collateral ligament. RESULTS - SUBSTUDIES (INVESTIGATION OF PREFERENCES): The central finding for this substudy was that, on average and within the range specified, choices in this group of potential patients were not significantly influenced by variation in the chance of avoiding surgery. CONCLUSIONS - IMPLICATIONS FOR HEALTHCARE: The evidence presented in this report supports the conclusions that the use of MRI in patients presenting at DGHs with chronic knee problems in whom arthroscopy was being considered did not increase NHS costs overall, was not associated with significantly worse outcomes and avoided surgery in a significant proportion of patients. CONCLUSIONS - RECOMMENDATIONS FOR FURTHER RESEARCH (IN PRIORITY ORDER): (1) The trial data demonstrated that the use of MRI in patients with chronic knee problems reduced the need for surgery. However, the link between diagnostic processes and changes in health outcome is indirect and the finding of no-MRI-related effect on health outcome may, therefore, be a consequence of the limited power of the trial. Further research to confirm (or contradict) these findings would be valuable. (2) The investigation of diagnostic accuracy involved comparison with a reference diagnosis established by a panel of two clinical members of the research team. It would be interesting to explore the extent to which the results would differ using an external panel. (3) The result from the preference study, indicating that the potential diagnostic/therapeutic impact of knee MRI was not highly valued, is a surprising finding that would be important to explore in general public or patient populations. (4) The focus for the trial-based aspects of this research was the DGH and patients presenting with chronic knee problems who were being considered for surgery. Care should be taken in generalising from these results to other patient groups (e.g. acute knee injuries) or to other settings (e.g. specialist centres). Further clinical trials would be required in order to answer such questions.

Adolescent↗
PubMed1999

Hyaluronan forms specific stable tertiary structures in aqueous solution: a 13C NMR study.

13C NMR spectra of aqueous solutions of hyaluronan (HA) of high molecular mass, before and after digestion with testicular hyaluronidase, and of hyaluronan methyl ester were obtained at 125.8 MHz. Carbonyl peaks were assigned by using selective decoupling techniques. Spectra of digested and undigested HA showed sharp signals, except for that assigned to the acetamido carbonyl carbon in the high polymer, which was much broadened. The decreased mobility of this C==O, thus demonstrated, was caused by restricted rotation. As part of the rigid CO---NH unit, rotation of NH was therefore similarly restricted, probably because of an intermolecular H bond from NH to carboxylate groups on neighbouring HA molecules. This bond was confirmed by comparing esterified HA with unmodified HA. Methyl esterification of carboxylates was accompanied by changes in acetamido C==O resonances consistent with increased mobility of CO---NH groups. Ester C==O resonances were sharp, proving that they did not participate in sterically restricted structures such as the proposed H bonds involving unesterified carboxylate groups. C==O resonances report on the environments and on the interrelationships of amide and carboxylate groups. A detailed structure suggested for high-molecular-mass HA in aqueous solution takes account of NMR and x-ray fiber diffraction data. Antiparallel HA chains overlap in meshworks stabilized by specific H bonds and hydrophobic bonds. This highly cooperative structure, formally equivalent to beta-sheets seen in proteins, is not stable in low-molecular-mass HA solution. The results relate to structures proposed for shape modules in extracellular matrix involving chondroitin and keratan sulfates, which resemble HA in their stereochemistry.

Animals↗
PubMed1995

Comparison of secondary structures in water of chondroitin-4-sulfate and dermatan sulfate: implications in the formation of tertiary structures.

Chondroitin-4-sulfate (CS4) and dermatan sulfate (DS) were examined in D2O solution, with or without NaCl, by NMR at 300 MHz, to investigate the physicochemical consequences of epimerization of glucuronate (GlcUA in CS4) to iduronate (IdoUA in DS). Nuclear Overhauser effects (NOEs) and spin-lattice relaxation times following selective and nonselective inversion were measured at up to 70 degrees C. (1) NOEs confirmed 4C1 conformations of sugar rings in N-acetylgalactosamine and GlcUA, and 1C4 or 2S0 in IdoUA. Conflict between NMR data and periodate oxidation kinetics over IdoUA conformations is resolvable by postulating conversion of monodentate periodate-1C4 complexes to conformations in which periodate oxidation can procede. (2) Pairs of glycosidic protons in CS4 and DS showed strong NOEs, implying that stretches of 2-fold helix were present, with carboxylate and acetamido groups close to each other on the same side of tapelike molecules, extending previous work in dimethyl sulfoxide solution. CS4 and DS have large hydrophobic patches in this configuration, similar to those in keratan sulfate and hyaluronan. (3) Selective and nonselective inversion-recoveries implied similar segmental and backbone mobilities and hence flexibilities in CS4 and DS. This is discussed in terms of intrinsic flexibility of glycosidic conformations, modified by hydrogen-bonded arrays. (4) We postulate that hydrophobic and hydrogen bonding drives DS self-aggregation. Stronger self-aggregation of DS compared with CS4 is attributed to increased intermolecular hydrogen-bonding in DS, secondary to decreased intramolecular hydrogen-binding. This is partly because the axial OH groups in 1C4 IdoUA cannot hydrogen-bond to neighboring sugars as can the equatorial OH groups in GlcUA of CS4.

Animals↗
PubMed1988

A water molecule participates in the secondary structure of hyaluronan.

The structure of hyaluronan was investigated in water/dimethyl sulphoxide mixtures by using high-field n.m.r. and space-filling molecular models. The secondary structure previously established in detail in 'dry' dimethyl sulphoxide [Heatley, Scott & Hull (1984) Biochem. J. 220, 197-205] undergoes changes on addition of water, compatible with the incorporation of a water bridge between the uronate carboxylate and acetamido NH groups. Molecular models show that such a configuration is highly probable, and saturation-transfer experiments yield rates of NH proton exchange that support this proposed structure. The existence of two distinct stable configurations for hyaluronan, in water-rich and water-poor conditions respectively, may have biological implications, e.g. during its biosynthesis in cell membranes. There are extensive hydrophobic regions in both forms, which may be important for interactions with e.g., membranes, proteins and itself.

Dimethyl Sulfoxide↗
PubMed1984

Secondary structure of hyaluronate in solution. A 1H-n.m.r. investigation at 300 and 500 MHz in [2H6]dimethyl sulphoxide solution.

The 1H-n.m.r. spectra of solutions in [2H6]dimethyl sulphoxide of the sodium salts of tetra-, hexa- and octa-saccharides prepared from hyaluronate by testicular-hyaluronidase digestion were examined at 300 and 500 MHz. The signals from hydroxy groups at positions 2 and 3 in the glucuronic acid moiety were assigned. Their chemical shifts and associated temperature-dependencies, as well as their coupling constants, depended on whether or not the uronic acid was at the non-reducing end. Deviations from the 'normal' pattern of hydroxy-group proton n.m.r. behaviour were attributable to participation in hydrogen bonds, either to the acetamido carbonyl oxygen atom or the pyranose ring oxygen atom of neighbouring N-acetylhexosamine moieties. A secondary structure, containing four different hydrogen bonds per trisaccharide unit of glucuronsyl-hexosaminyl-glucuronic acid, was demonstrated. This is the first complete and detailed secondary structure to be established for hyaluronate in any solvent. Hyaluronate is compared with chondroitin sulphate, dermatan sulphate, heparan sulphate and keratan sulphate in their potential to form secondary structures with features in common. The significance of the details of the structure to its overall stability, and the probability of their persistence into aqueous environments, are discussed. The presence of all or most of the secondary structure in glycosaminoglycuronans is correlated with a space-filling function in the tissue, and with a high carbohydrate content in the parent proteoglycan in the case of the chondroitin sulphates.

Carbohydrate Conformation↗
PubMed1984

Interaction of some polyhexamethylene biguanides and membrane phospholipids in Escherichia coli.

The interaction between some polyhexamethylene biguanides and the cell envelope of Escherichia coli has been investigated. An amine-ended dimer, (AED, n = 2), a polydisperse mixture (ICI plc) available as the active ingredient of Vantocil IB, (PHMB, n = 5.5), and a high molecular weight fraction, (HMW, n = greater than or equal to 10) of PHMB were used. The sensitivity of batch cultures depleted of magnesium (M-dep), phosphorus (P-dep) or glycerol (C-dep) towards the biocides was assessed by monitoring the rate and extent of potassium ion leakage. P-dep suspensions were particularly resistant to all these agents and possessed less than half the quantity of phospholipid of other cell types. This was compensated for by a proportionate increase in fatty acid and neutral lipid content of the cells. The reduction in phospholipid content was accounted for by decreases in phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). Diphosphatidylglycerol (DPG) and phosphatidylserine (PS) content of the cultures remained unaffected by the depleting nutrient. Fourier-transform n.m.r. spectroscopy was used to study proton nuclei during the interaction of HMW, AED and PHMB with various phospholipid-vesicle preparations. The results strongly suggest that the biocides acted preferentially on the acidic phospholipids PG and DPG, rather than towards PE or PS. Resistance of P-dep cultures therefore reflected reductions in PG content. A molecular basis for the interaction of these compounds and membranes is proposed.

Biguanides↗
PubMed1983

Secondary structure of chondroitin sulphate in dimethyl sulphoxide.

1H NMR spectra were obtained in fully deuterated dimethyl sulphoxide of sodium chondroitin 4-sulphate and of the tetrasaccharide, hexasaccharide and octasaccharide prepared from it. Two types of NH resonance were observed, at 7.6 ppm and 8.8 ppm. The latter was the only one in the polymer spectrum, whereas both were present in the oligomer spectra: N-acetylchondrosinate produced only the 7.6-ppm signal. The upfield resonance (7.6 ppm) is characteristic of "normal", monomeric acetamido sugars and disaccharides, while the downfield resonance (8.8 ppm) suggests a hydrogen-bonded NH. The elongation of disaccharide to tetrasaccharide produces a new environment, involving a hydrogen bond at the non-reducing disaccharide NH. A structure, with three hydrogen bonds per tetrasaccharide unit, is proposed which accounts for the quantitative and qualitative aspects of the NMR spectra of polymers and oligomers. A laser light-scattering study showed that sodium chondroitin 4-sulphate has the same molecular weight in water as in dimethyl sulphoxide. The observed hydrogen bonds are therefore intramolecular, as required by the proposed structure, and probably exist in water as well as in dimethyl sulphoxide.

Chemical Phenomena↗
PubMed1982

Detection of secondary structure in glycosaminoglycans via the H n.m.r. signal of the acetamido NH group.

Two simple methods for dissolving salts of acid glycosaminoglycans with inorganic cations (e.g. Li+ and Na+) in dry dimethyl sulphoxide are described. Complete n.m.r. spectra of, e.g., Na+ and Li+ salts of chondroitin sulphate and keratan sulphate were obtained on these solutions. In [2H6]dimethyl sulphoxide the NH resonance of 2-acetamido-2-deoxy hexosides is in the range 7.2-8.0 delta, but is downfield (8.3-9.3 delta) when the NH is H-bonded to -CO2-. Heparan sulphate shows two NH resonances, of which one (at 8.3 delta) is probably indicative of H-bonding. Space-filling models show that a very close approach of NH to -CO2- across the alpha-glucosaminidic bond is possible, and a solution configuration for heparan sulphate is proposed. The n.m.r. results are entirely compatible with interpretations of periodate-oxidation kinetics, based on H-bonded secondary structures present in hyaluronate and chondroitin sulphates, but not in dermatan (or keratan) sulphate.

Acetamides↗
PubMed1982

Secondary structure in glycosaminoglycuronans: N.M.R. spectra in dimethyl sulphoxide of disaccharides related to hyaluronic acid and chondroitin sulphate.

1H-N.m.r.spectra for solutions in dimethyl sulphoxide-d6 of disaccharides related to hyaluronate and chondroitin sulphate are compared with those of their methylated derivatives. All resonances, including those of HO and HN groups, have been assigned. The temperature and concentration dependences suggest that HO-4 of the hexosamine residue in hyalobiouronate (but not that in chondrosinate) is hydrogen-bonded to O-5 of the uronic acid residue. The resonance of HO-2 of the uronate residue of chondrosinate also shows anomalies that may arise from intra-residue hydrogen-bonding. These findings confirm the existence of some features previously suggested to be present in glycosaminoglycuronan polymers. The resonance of HO-4 of the uronate residue in the disaccharides and in sodium (methyl alpha-D-glucopyranosid)uronate behaves as though there was a hydrogen bond between the carboxylate group and HO-4.

Carbohydrate Conformation↗
PubMed1982

Synthesis and dopaminergic properties of some exo- and endo-2-aminobenzonorbornenes designed as rigid analogue of dopamine.

Stereospecific syntheses of exo-2-amino-5,6-dihydroxybenzonorbornene (11f), exo-2-amino-6,7-dihydroxybenzonorbornene (11h), exo-2-amino-7,8-dihydroxybenzonorbornene (11g), and endo-2-amino-6,7-dihydroxybenzonorbornene (14d), rigid analogues of dopamine, are described. Compounds 11 h and 14d, their N-methyl (11i and 11j) and N,N-dimethyl (14i and 14j) derivatives, and compounds 11f and 11g were inactive as dopamine agonists when evaluated for dopaminergic activity by their ability to induce stereotyped behavior in mice after subcutaneous injection and by their ability to cause hyperactivity in rats after bilateral injection into the nucleus accumbens. However, compounds 11f, 11g, 11h, and the N-methyl derivatives 11i and 14d were all effective in displacing [3H]-2-amino-6,7-dihydroxytetralin ([3H]ADTN) and [3h[-N-n-propylnorapomorphine ([3H]NPA) from rat striatal membranes.

Animals↗
PubMed1981

Secondary structures of hyaluronate and chondroitin sulphates. A 1H n.m.r. study of NH signals in dimethyl sulphoxide solution.

1H n.m.r. spectra in [2H6]dimethyl sulphoxide of dodecyltrimethylammonium salts of chondroitin sulphates and hyaluronate, or sodium salts of oligomers from hyaluronate, showed unambiguous NH signals. The acetamido NH occurs in two different environments: environment I ('normal') in simple sugars, and environment II (hydrogen-bonded NH) appearing in tri- or tetrasaccharides, indicating a secondary structure in hyaluronate (and some chondroitin sulphates) involving a hydrogen-bonded acetamido NH.

Chondroitin↗
PubMed1979

1H nuclear-magnetic-resonance spectra of the methyl group of the acetamido moiety and the structure of acid glycosaminoglycans in solution.

The 1H resonances of the methyl group in the acetamido moiety of several types of glycosaminoglycans are reported at 300 MHz in 2H2O. Dermatan sulphates with various L-iduronate/D-glucuronate ratios are compared with chrondroitin sulphates with various contents and positions of substitution of sulphate esters. Hyaluronate oligomers are compared with 2-acetamido-2-deoxy-D-glucose, and with heparan sulphate and keratan sulphate. The major determinant of the chemical shift of the acetamido methyl resonance is the closeness of approach between carboxy groups and the acetamido group, in agreement with chemical evidence based on periodate-oxidation kinetics.

Acetamides↗
PubMedDate not supplied

In vivo corrosion of 316L stainless-steel hip implants: morphology and elemental compositions of corrosion products.

Eleven surgically retrieved stainless steel implants showing varying degrees of surface corrosion were examined to characterize the morphology and composition of corrosion products. The implants were fabricated to the specification AISI316L (Muller) and BS 3531 pt 1 1971-78 (Charnley). They had been in place for 9-21 y (Mean :13 y) and failures were due to aseptic loosening. The morphology and chemical compositions of corrosion products were recorded using scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX). Nine implants had areas of corrosion covering 1-5 cm of the stem, partially or all round. Corrosion existed in layers. The layers consisted either of chromium in association with sulfur, or iron in association with phosphorus. Variable amounts of calcium and chlorine were also present in all layers. Nickel, which makes up 13% of the alloy, was persistently absent. The presence and extent of corrosion was independent of the alloy composition and could not be related to the duration of implantation.

Aged↗