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Biomedical subjects

S Bailey

Publications and source records attributed to S Bailey.

At least 145 records · Page 8Linked to original sources
PubMed1993

Does prediction of outcome alter patient management?

A patient's prognosis is a key factor for the clinicians involved in management. We set out to determine if provision of computer-based predictions of outcome after severe head injury resulted in measurable changes in patient management. In particular, we wondered whether introduction of the predictive system would alter the relation between severity of injury and "intensity" of management. 1025 patients admitted to four British neurosurgical units between 1986 and 1989 following a severe head injury, and who were either in coma for 6 h or had an operation for acute intracranial haematoma, were studied. Specified aspects of intensive management were recorded and all patients were followed up after six months. The study had three phases: a baseline period of at least one year before the introduction of computer-based outcome prediction, one year when predictions were provided at specified times, and a final six months when prediction was withdrawn. While predictions were being provided, there was an increase in the use of specified aspects of intensive care in patients predicted to have a good outcome, but a 39% reduction in the use of these same aspects of intensive care in patients predicted to have the worst outcome. There was no evidence that the provision of predictions affected overall outcome, length of stay, or the recording of explicit decisions to limit treatment. We have demonstrated that the introduction of a routine prediction service can alter patient management.

Adult↗
PubMed1993

Substrate interactions between trypanothione reductase and N1-glutathionylspermidine disulphide at 0.28-nm resolution.

The enzyme trypanothione reductase has been identified as a prime target for the rational design of inhibitors which may have clinical use in the treatment of tropical diseases caused by the genera Trypanosoma and Leishmania. To aid the design or identification of new inhibitors of this enzyme we have elucidated the structural detail of a trypanothione reductase complexed with one of the naturally occurring substrates, N1-glutathionylspermidine disulphide, by single-crystal X-ray diffraction methods at 0.28-nm resolution. The model for the Crithidia fasciculata enzyme-substrate complex has an R-factor of 14.8% and root-mean-square deviations of 0.0015 nm and 3.3 degrees on bond lengths and angles respectively. Hydrogen bonding and van der Waals interactions between the enzyme and substrate are dominated by the amino acid side chains. The substrate binds in a rigid active site such that one glutathione moiety is in a V-shape, the other in an extended conformation. One spermidine moiety binds closely to a hydrophobic patch in the active site formed by a tryptophan and a methionine. Distances between the methionine S delta and the terminal N of this spermidine suggest that a hydrogen bond may supplement the hydrophobic interactions in this part of the active site.

Animals↗
PubMed1993

Randomised trial of targeted chemotherapy with lipiodol and 5-epidoxorubicin compared with symptomatic treatment for hepatoma.

Lipiodol injected into the hepatic artery is selectively retained in hepatomas so has been used as a vehicle for cytotoxic drugs. This study compared treatment with 5-epidoxorubicin emulsified in lipiodol and infused into the hepatic artery with symptomatic treatment alone in a randomised trial. Of 136 patients with hepatoma 78 (57%) were not eligible, eight (6%) refused to take part, and 50 entered the trial (chemotherapy: n = 25, symptomatic treatment: n = 25). The two groups had similar prognostic indices. Seven of 25 patients allocated to chemotherapy were unable to receive it. The slight survival disadvantage associated with chemotherapy was not significant (median survival 48 days compared with 51 days, log rank chi 2 = 0.07, p > 0.05). Patients given chemotherapy spent significantly longer in hospital, however (median three days compared with one, p = 0.0008). Changes in symptoms and indices of tumour growth did not differ significantly between the two groups. It is concluded that infusion of 5-epidoxorubicin emulsified in lipiodol for hepatoma increased morbidity but did not affect survival. In addition, most patients were unsuitable for this treatment because of advanced disease. The patients in the trial had a short median survival time so the conclusions may not be valid for other patients with hepatoma.

Adolescent↗
PubMed1992

Active site of trypanothione reductase. A target for rational drug design.

The X-ray crystal structure of the enzyme trypanothione reductase, isolated from the trypanosomatid organism Crithidia fasciculata, has been solved by molecular replacement. The search model was the crystal structure of human glutathione reductase that shares approximately 40% sequence identity. The trypanosomal enzyme crystallizes in the tetragonal space group P4(1) with unit cell lengths of a = 128.9 A and c = 92.3 A. The asymmetric unit consists of a homodimer of approximate molecular mass 108 kDa. We present the structural detail of the active site as derived from the crystallographic model obtained at an intermediate stage of the analysis using diffraction data to 2.8 A resolution with an R-factor of 23.2%. This model has root-mean-square deviations from ideal geometry of 0.026 A for bond lengths and 4.7 degrees for bond angles. The trypanosomid enzyme assumes a similar biological function to glutathione reductase and, although similar in topology to human glutathione reductase, has an enlarged active site and a number of amino acid differences, steric and electrostatic, which allows it to process only the unique substrate trypanothione and not glutathione. This protein represents a prime target for chemotherapy of several debilitating tropical diseases caused by protozoan parasites belonging to the genera Trypanosoma and Leishmania. The structural differences between the parasite and host enzymes and their substrates thus provides a rational basis for the design of new drugs active against trypanosomes. In addition, our model explains the results of site-directed mutagenesis experiments, carried out on recombinant trypanothione reductase and glutathione reductases, designed by consideration of the crystal structure of human glutathione reductase.

Amino Acid Sequence↗
PubMed1992

Initiating a crystallographic study of a class II fructose-1,6-bisphosphate aldolase.

We have reproducibly crystallized the metal-dependent Class II fructose-1,6-bisphosphate aldolase from Escherichia coli. Crystals in the shape of truncated hexagonal bipyramids have unit cell dimensions of a = b = 78.4 A, c = 290.6 A and are suitable for a detailed structural analysis. The space group has been identified as P6(1)22 or enantiomorph. Data sets to approximately 2.9 A resolution have been recorded using both the Rigaku R-AXIS IIc image plate area detector coupled to a copper target rotating anode X-ray source and using the MAR image plate systems with synchrotron radiation at the EMBL outstation DESY in Hamburg, and at S.R.S. Daresbury. Diffraction beyond 2.5 A has been observed when large freshly grown crystals are used with the synchrotron beam. A data set to this resolution has been collected. Several putative heavy-atom derivative data sets have also been measured using synchrotron radiation facilities and analysis of these data sets is in progress.

Crystallization↗
PubMed1992

The association between meningitis and dural puncture in bacteremic rats.

Clinicians have long been concerned that performance of spinal anesthesia during a period of bacteremia may result in the subsequent development of meningitis. In order to determine whether such an association exists, percutaneous dural puncture was performed in 40 animals during a period of Escherichia coli bacteremia. Twenty-four hours later, spinal fluid was obtained for final analysis by surgically draining the cisterna magna. Twelve animals had E. coli recovered from the surgically drained spinal fluid. Only animals with a circulating bacterial count of at least 50 CFU/ml developed meningitis. Microscopic examination of the brains and spinal cords of animals with infected cerebrospinal fluid showed evidence of central nervous system infection. Bacteremic animals not undergoing percutaneous dural puncture always had sterile spinal fluid (n = 40). Cisternal puncture in the absence of bacteremia did not result in infection (n = 30). Treatment with a single dose of gentamicin before the dural puncture eliminated the risk of meningitis after dural puncture in 30 bacteremic animals. These results demonstrate that dural puncture is associated with the development of meningitis in rats, provided the animals are bacteremic at the time of the puncture. However, antibiotic treatment before the dural puncture appears to eliminate this risk.

Anesthesia, Spinal↗
PubMed1992

Position change: effects on electrocardiograms in COPD patients.

The effects of the supine and the 45 degrees angle position were tested for the effect of electrocardiograms of 28 COPD patients. No significant differences were found in five EKG parameters: AXIS, PR interval, QRS duration, QT interval, and diagnostic interpretation. A comfort scale was administered to the sample population. Most (89.2%, N = 25) of the patients preferred the 45 degrees angle position; 17.2% (N = 2) felt the supine position to be more comfortable. Implications for research, theory, and practice are discussed.

Adult↗
PubMed1992

Human monoclonal antibodies specific for blood group antigens demonstrate multispecific properties characteristic of natural autoantibodies.

A panel of 72 human monoclonal antibodies with specificities for blood group antigens, A, Rh D, Rh C, Rh c, Rh E, Rh e, Rh G, Jka and Jkb, has been established from the peripheral blood of deliberately immunized donors. Previous work has established that the antibodies are highly specific for their respective blood group antigens, and a number of them are in routine clinical use as blood grouping reagents. This panel was screened for reactivity against six unrelated foreign and autoantigens by ELISA, for rheumatoid factor activity by ELISA and agglutination techniques, and for reactivity with a number of different tissues by immunofluorescence. Binding of the monoclonal antibodies to unrelated exo- and autoantigens was commonly seen amongst the antibodies of the IgM class, and to a lesser degree amongst the IgG class, with reaction patterns similar to those given by natural autoantibodies. Only five of the IgM antibodies failed to demonstrate any unexpected cross-reactivities and these included 1/13 anti-D, 2/7 anti-E, 1/13 anti-c and 1/2 anti-A. We propose that rather than natural autoantibodies representing a distinct population of immunoglobulins, multispecificity (polyspecificity, or polyreactivity) may be a feature of antibodies produced in response to exogenous antigens. The implications of this for the study of autoantibodies are discussed.

Antibodies, Monoclonal↗
PubMed1991

Effect of intracoronary stenting on intimal dissection after balloon angioplasty: results of quantitative and qualitative coronary analysis.

The effect of the Palmaz-Schatz stent on the angiographic appearance and residual luminal stenosis in patients with intimal dissection after balloon angioplasty was evaluated in 84 consecutive patients (90 lesions). Coronary angiography was performed before angioplasty, after conventional angioplasty and after stent implantation. The degree of intimal disruption was assessed as follows: grade 0, no dissection; grade 1, simple dissection (intraluminal linear defect or extraluminal cap extravasation); or grade 2, complex dissection (nonlinear spiral defect or luminal defect with multiple irregular borders). Quantitative coronary analysis of digitized cineangiograms was performed with use of a computerized automatic edge detection algorithm. After balloon angioplasty, 31 (34%) of 90 lesions demonstrated intimal dissection (18 simple, 13 complex). After stent implantation, intimal dissection improved by greater than or equal to 1 grade in 29 (94%) of the 31 lesions with 27 (87%) reduced to grade 0 (that is, no dissection). Dissection grade improved after stenting in 16 (89%) of 18 simple dissections and in all 13 complex dissections. Mean diameter stenosis was 77 +/- 17% before angioplasty, 47 +/- 17% after angioplasty and 14 +/- 10% after stenting (before angioplasty vs. after angioplasty and after angioplasty vs. after stenting, p less than 0.0001). In conclusion, intracoronary stenting is effective in reducing the residual luminal stenosis and in improving the angiographic appearance of intimal dissections after conventional balloon angioplasty.

Adult↗
PubMed1991

Synthesis and antiviral activity of 9-alkoxypurines. 2. 9-(2,3-Dihydroxypropoxy)-, 9-(3,4-dihydroxybutoxy)-, and 9-(1,4-dihydroxybut-2-oxy)purines.

Reaction of alkenoxyamines (3,5) or (R,S)-, (R)-, and (S)-hydroxy-protected derivatives of hydroxyalkoxyamines (20a,b, 37a-c) with 4,6-dichloro-2,5-diformamidopyrimidine (4) and cyclization of the resultant 6-[(alkenoxy)amino]-and 6-(alkoxyamino)pyrimidines (6,7,21a,b, 38a,b,c) by heating with diethoxymethyl acetate afforded 9-alkenoxy- and 9-alkoxy-6-chloropurines (9,10,22a,b, 39a-c, 40a). These were subsequently converted to 9-(2,3-dihydroxypropoxy), 9-(3,4-dihydroxybutoxy), and 9-(1,4-dihydroxybut-2-oxy) derivatives of guanine and 2-aminopurine (13-16, 25-28, 41a-c, 42a). A 2-amino-6-methoxypurine derivative (17) was also prepared. The racemic guanine derivative 13 showed potent and selective activity against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), but was less active against varicella zoster virus (VZV). Its antiviral activity is attributable to the S isomer (28), which was found to be more active than acyclovir against HSV-1 and HSV-2 and about 4 times less active than acyclovir against VZV. The S enantiomer of 9-(1,4-dihydroxybut-2-oxy)guanine (41c) also showed noteworthy antiviral activity in cell culture. Although this acyclonucleoside (41c) is only weakly active against HSV-1 and inactive against HSV-2, it is about twice as active as acyclovir against VZV.

Antiviral Agents↗
PubMed1991

Operative treatment of spinal fractures with the AO internal fixator.

A multicentered prospective trial to investigate the usefulness of the AO spinal internal fixator for the treatment of thoracolumbar fractures and fracture-dislocations was undertaken. This pedicle screw-rod system was effective in stabilizing a variety of unstable fracture patterns. It was effective in decompressing the canal of retropulsed bony fragments associated with burst fractures. By the use of this implant, sagittal plane deformity was easily corrected.

Adult↗
PubMed1990

Phylogenetic analysis and secondary structure of the Bacillus subtilis bacteriophage RNA required for DNA packaging.

An unusual RNA molecule encoded by the Bacillus subtilis bacteriophage phi 29 is a structural component of the viral prohead and is required for the ATP-dependent packaging of DNA. Here we report a model of secondary structure for this prohead RNA developed from a phylogenetic analysis of the primary sequences of prohead RNAs of related phages. Twenty-nine phages related to phi 29 were found to produce prohead RNAs. These RNAs were analyzed by their ability to replace phi 29 RNA in in vitro phage assembly, by Northern blot hybridization with a probe complementary to phi 29 RNA, and by partial and complete sequence analyses. These analyses revealed four quite different sequences ranging in length from 161 to 174 residues. The secondary structure deduced from these sequences, in agreement with earlier observations, indicated that prohead RNA is organized into two domains. The larger 5'-domain (Domain I) is composed of 113-117 residues and contains four helices. Three of these helices appear to be organized into a central stem that is interrupted by two unpaired loops and the fourth helix and loop. The smaller 3'-domain (Domain II) is composed of 40-44 residues and consists of two helices. Domains I and II are separated by 8-13 unpaired residues. Nuclease cleavage occurs readily in this single-stranded joining region, and this cleavage allows the subsequent separation of the two RNA domains. The separated Domain I is fully active in DNA packaging in vitro. The functional significance and biological role of Domain II are unknown. The phylogenetic secondary structure model provides a basis for further analysis of the role of this RNA in bacteriophage morphogenesis.

Bacillus subtilis↗
PubMed1990

Rotation function studies of human C-reactive protein.

Rotation function studies of two tetragonal crystal forms of human C-reactive protein have confirmed the pentameric structure of the molecule. The two crystal forms have space groups P4122 (I) and P4222 (II) with closely similar unit cells and are often twinned together. Investigation of the crystallization conditions indicates that dissociation heterogeneity has been a major limiting factor in the reproducible growth of good single crystals. The orientation of the pentameric molecule is shown to be almost identical in both forms, about the axial direction omega = 57 degrees, phi = 45 degrees, i.e. 57 degrees away from c in the (110) plane.

C-Reactive Protein↗
PubMed1990

Steps towards cost-benefit analysis of regional neurosurgical care.

OBJECTIVE: To determine the cost of averting death or severe disability by neurosurgical intervention. DESIGN: Retrospective analysis of one year's admissions for neurosurgery; comparison of outcome with expected outcome in the absence of neurosurgical intervention and with the cost of neurosurgery. SETTING: Wessex Neurological Centre. PATIENTS: 1026 Patients were admitted to the neurosurgical service in 1984. Of 1185 admissions, 978 case records were available and outcome was known in 919. MAIN OUTCOME MEASURES: Outcome was assessed with the Glasgow outcome scale, modified as necessary, from the case notes, or by letter follow up to the general practitioner. Expected outcomes for each of the 54 diagnoses were derived from both published reports where available and an expert panel of 18 consultant neurosurgeons. The cost of the neurosurgical service for 1983-4 was known from a separate study and the cost per patient was calculated using the length of stay. RESULTS: The cost of neurosurgery in 1983-4 was 1.8 million pounds. In all, 243 deaths or severe disabilities were estimated to have been averted at an average cost of 7325 pounds (range 5000 pounds to 70,000 pounds). The overall cost per quality adjusted life year (QALY) was 350 pounds (range 34 pounds to greater than 400,000 pounds). The cost of long term care for severely disabled survivors is at least 18-fold greater than the cost of neurosurgical intervention to avert such disability. CONCLUSIONS: In Britain neurosurgery is not expensive in comparison with the costs and benefits of other areas of medicine, and the cost per QALY is unexpectedly low except for severe diffuse head injury, malignant brain tumors, and cerebral metastases. The neurosurgical budget should be assessed in the context of managing a patient in hospital and subsequently in the community.

Brain Diseases↗
PubMed1990

Preliminary crystallographic study of C-reactive protein from Limulus polyphemus.

Crystals of C-reactive protein from Limulus polyphemus have been grown both with and without calcium. The space group for the calcium-free crystals is I422 or I4(1)22, and the cell parameters are a = b = 173.33 (4) A, c = 98.81 (3) A. The crystals diffract to at least 2.8 A resolution and are suitable for detailed structural studies.

Animals↗