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Biomedical subjects

C Steward

Publications and source records attributed to C Steward.

At least 19 recordsLinked to original sources
PubMed2006

Standards for head injury management in acute hospitals: evidence from the six million population of the Eastern region.

OBJECTIVES: To develop standards of care for head injury and thereby identify and prioritize areas of the service needing development; to report the findings from a survey of compliance with such standards in the Eastern region of UK. METHODS: The standards were collaboratively developed through an inclusive and iterative process of regional surveys, multidisciplinary conferences, and working groups, following a method similar to that used by the Society of British Neurological Surgeons. The standards cover seven topics relating to all aspects of service delivery, with standards within each objective. Each standard has been designated a priority level (A, B, or C). The standards were piloted using a self-assessment questionnaire, completed by all 20 hospitals of the Eastern region. RESULTS: Full compliance was 36% and a further 30% of standards were partially met across the region, with some areas of service delivery better than others. Seventy eight per cent of level A standards were either fully or partially met. Results were better in the north of the region compared with the south. CONCLUSION: A survey of compliance with the head injury standards indicate that, with their whole systems approach and subject to further refinement, they are a useful method for identifying deficiencies in service provision and monitoring for quality of care both within organisations and regionally.

Craniocerebral Trauma↗
PubMed2005

Bacterial adhesion to bisphosphonate coated hydroxyapatite.

Staphylococcus aureus (S. aureus) is commonly associated with microbial infection of orthopaedic implants. Such infections often lead to osteomyelitis, which may result in failure of the implant due to localised bone destruction. Bacterial adhesion and subsequent colonisation of the device may occur as a consequence of contamination during surgery, or by seeding from a distant site through the blood circulation. Coating of the hydroxyapatite (HA) ceramic component of artificial hip joints with the bisphosphonates clodronate (C) and pamidronate (P) has been proposed as a means to minimise osteolysis and thereby prevent loosening of the implant. However, the effect of the bisphosphonate coating on bacterial adhesion to the HA materials must be determined before this approach can be implemented. In this study coated HA materials were incubated with the S. aureus and the number of adherent bacteria determined using the Modified Vortex Device (MVD) method. The number of bacteria adherent to the P coated HA material was significantly greater than that adherent to uncoated HA (60-fold increase) or to the C coated HA (90-fold increase). Therefore, even though earlier studies suggested that P bound to HA may improve osseointegration, the results presented would suggest that the use of this coating may be limited by the potential increased susceptibility of the coated device to infection.

Bacterial Adhesion↗
PubMed2004

Mapping rehabilitation resources for head injury.

Several reports have pointed to the unevenness in the UK of services for rehabilitation after head injury. A study was conducted in the Eastern Region of England to define the key stages in recovery and rehabilitation, by an iterative process of questionnaire, interview and consensus conference. Findings were translated into a draft set of maps showing current availability of services which were revised after feedback. Working groups then developed a set of definitions and classification codes for each stage of rehabilitation which were likewise disseminated for feedback. The maps were then redrafted to correspond with the definitions together with a flowchart of potential head injury rehabilitation services. The definitions were piloted at a regional neurosurgery unit and a rehabilitation hospital. Core services for neurorehabilitation region-wide were found to be variable and uncoordinated with fragmented and inequitable allocation of resources. The definitions and mapping system that emerged from this study should facilitate the design of care pathways for patients and identify gaps in the services.

Craniocerebral Trauma↗
PubMed2001

Differential inhibition of [3H]-oxotremorine-M and [3H]-quinuclinidyl benzilate binding to muscarinic receptors in rat brain membranes with acetylcholinesterase inhibitors.

The potential interaction of acetylcholinesterase inhibitors with cholinergic receptors may play a significant role in the therapeutic and/or side-effects associated with this class of compound. In the present study, the capacity of acetylcholinesterase inhibitors to interact with muscarinic receptors was assessed by their ability to displace both [3H]-oxotremorine-M and [3H]-quinuclinidyl benzilate binding in rat brain membranes. The [3H]-quinuclinidyl benzilate/[3H]-oxotremorine-M affinity ratios permitted predictions to be made of either the antagonist or agonist properties of the different compounds. A series of compounds, representative of the principal classes of acetylcholinesterase inhibitors, displaced [3H]-oxotremorine-M binding with high-to-moderate potency (ambenonium>neostigmine=pyridostigmine=tacrine>physostigmine> edrophonium=galanthamine>desoxypeganine) whereas only ambenonium and tacrine displaced [3H]-quinuclinidyl benzilate binding. Inhibitors such as desoxypeganine, parathion and gramine demonstrated negligible inhibition of the binding of both radioligands. Scatchard plots constructed from the inhibition of [3H]-oxotremorine-M binding in the absence and presence of different inhibitors showed an unaltered Bmax and a reduced affinity constant, indicative of potential competitive or allosteric mechanisms. The capacity of acetylcholinesterase inhibitors, with the exception of tacrine and ambenonium, to displace bound [3H]-oxotremorine-M in preference to [3H]quinuclinidyl benzilate predicts that the former compounds could act as potential agonists at muscarinic receptors. Moreover, the rank order for potency in inhibiting acetylcholinesterase (ambenonium>neostigmine=physostigmine =tacrine>pyridostigmine=edrophonium=galanthamine >desoxypeganine>parathion>gramine) indicated that the most effective inhibitors of acetylcholinesterase also displaced [3H]-oxotremorine-M to the greatest extent. The capacity of these inhibitors to displace [3H]-oxotremorine-M binding preclude their utilisation for the prevention of acetylcholine catabolism in rat brain membranes, the latter being required to estimate the binding of acetylcholine to [3H]-oxotremorine-M-labelled muscarinic receptors. However, fasciculin-2, a potent peptide inhibitor of acetylcholinesterase (IC50 24 nM), did prevent catabolism of acetylcholine in rat brain membranes with an atypical inhibition isotherm of [3H]-oxotremorine-M binding, thus permitting an estimation of the "global affinity" of acetylcholine (Ki 85 nM) for [3H]-oxotremorine-M-labelled muscarinic receptors in rat brain.

Animals↗
PubMed2000

Pediatric marrow transplantation for acute leukemia using unrelated donors and T-replete or -depleted grafts: a case-matched analysis.

A retrospective, case-matched analysis of the short-term toxicity, risk of GVHD and relapse as well as outcome in pediatric unrelated marrow transplantation was conducted by comparing recipients of T-replete and -depleted grafts in a two-center setting. Both groups contained 30 patients with acute leukemia matched by age at transplant, gender, primary diagnosis and disease status. Acute (90% vs 53%) and chronic (48% vs 0%) GVHD were more common among recipients of T-replete grafts. No significant differences in graft rejection/failure or viral infections were encountered between the two groups. Relapses were more prevalent (37% vs 15%) among recipients of T-depleted grafts. Outcome (EFS) was similar in the two groups. Consequently, in the analysis of transplant outcome, the higher risk of procedure-related, toxic complications among pediatric recipients of T-replete marrow grafts appears to be balanced by an increased risk of relapse among the recipients of T-depleted grafts.

Acute Disease↗
PubMed1999

Single-handed practices--their contribution to an undergraduate teaching network in the first year of the new curriculum.

OBJECTIVES: The new curriculum at King's College School of Medicine and Dentistry, which commenced in September 1996, requires all medical undergraduates to have a general practice placement throughout the 5 years of their medical education. DESIGN: This paper discusses recruitment, training and support of teaching practices for the new curriculum, reviews the distribution of single-handed general practices in the network and, via a selection of monitoring and evaluation procedures, discusses the implications of a policy which is inclusive of single-handed practices. The findings relate to the experience of the first semester of the first year of the new curriculum. It also examines the contributions that single-handed practices have made to the teaching network and the kind of support needed, if single-handed practices are to continue to contribute to the King's teaching network. SETTING: King's College School of Medicine and Dentistry. SUBJECTS: Medical undergraduates. RESULTS: The findings of this paper revealed that over a third of general practice provision is via single-handed practices in South-east London. Within the undergraduate teaching network, 10% of practices are single-handed. Students are welcomed and receive a learning experience comparable to those students in larger practices. Attendance at training events has proved difficult for some of these tutors, but the extra input from the department, in order to address this deficit, has not been onerous. Indeed, single-handed practices have not been unique with regard to difficulties in attendance at training events. CONCLUSIONS: The study concludes that single-handed practices can make satisfactory provision for undergraduates in the new curriculum and there is no evidence from this study to suggest otherwise.

Curriculum↗
PubMed1998

Assessment of resolution and intercenter reproducibility of results of genotyping Staphylococcus aureus by pulsed-field gel electrophoresis of SmaI macrorestriction fragments: a multicenter study.

Twenty well-characterized isolates of methicillin-resistant Staphylococcus aureus were used to study the optimal resolution and interlaboratory reproducibility of pulsed-field gel electrophoresis (PFGE) of DNA macrorestriction fragments. Five identical isolates (one PFGE type), 5 isolates that produced related PFGE subtypes, and 10 isolates with unique PFGE patterns were analyzed blindly in 12 different laboratories by in-house protocols. In several laboratories a standardized PFGE protocol with a commercial kit was applied successfully as well. Eight of the centers correctly identified the genetic homogeneity of the identical isolates by both the in-house and standard protocols. Four of 12 laboratories failed to produce interpretable data by the standardized protocol, due to technical problems (primarily plug preparation). With the five related isolates, five of eight participants identified the same subtype interrelationships with both in-house and standard protocols. However, two participants identified multiple strain types in this group or classified some of the isolates as unrelated isolates rather than as subtypes. The remaining laboratory failed to distinguish differences between some of the related isolates by utilizing both the in-house and standardized protocols. There were large differences in the relative genome lengths of the isolates as calculated on the basis of the gel pictures. By visual inspection, the numbers of restriction fragments and overall banding pattern similarity in the three groups of isolates showed interlaboratory concordance, but centralized computer analysis of data from four laboratories yielded percent similarity values of only 85% for the group of identical isolates. The differences between the data sets obtained with in-house and standardized protocols could be the experimental parameters which differed with respect to the brand of equipment used, imaging software, running time (20 to 48 h), and pulsing conditions. In conclusion, it appears that the standardization of PFGE depends on controlling a variety of experimental intricacies, as is the case with other bacterial typing procedures.

Bacterial Typing Techniques↗
PubMed1997

Evolution of extended-spectrum beta-lactam resistance (SHV-8) in a strain of Escherichia coli during multiple episodes of bacteremia.

Nine isolates of Escherichia coli were recovered from seven blood cultures over a period of 3 months from a 19-month-old female with aplastic anemia. Initial isolates were susceptible to extended-spectrum cephalosporins, including ceftazidime (MIC, < or = 0.25 microgram/ml), but gradually became resistant to this drug (MICs, > or = 128 micrograms/ml) and other cephalosporins and the monobactam aztreonam. Molecular typing methods, including plasmid profile analysis, pulsed-field gel electrophoresis, and arbitrarily primed PCR, indicated that the nine isolates were derived from a common ancestor. Dot blot hybridization and PCR analysis of total bacterial DNA using blaSHV- and blaTEM-specific DNA probes and primers identified the presence of a blaTEM beta-lactamase gene in all of the isolates and a blaSHV gene in the isolates with elevated ceftazidime MICs. Isoelectric focusing analysis of crude lysates showed that all nine isolates contained an enzyme with a pI of 5.4 corresponding to the TEM-1 beta-lactamase, and those isolates containing an SHV-type beta-lactamase demonstrated an additional band with a pI of 7.6. The first of the ceftazidime-resistant isolates appeared to hyperproduce the SHV enzyme compared to the other resistant isolates. DNA sequencing revealed a blaSHV-1 gene in the first ceftazidime-resistant isolate and a novel blaSHV gene, blaSHV-8, with an Asp-to-Asn substitution at amino acid position 179 in the remaining four isolates. Three of the ceftazidime-resistant isolates also showed a change in porin profile. The patient had received multiple courses of antimicrobial agents during her illness, including multiple courses of ceftazidime. This collection of blood isolates from the same patient appears to represent the in vivo evolution of resistance under selective pressure of treatment with various cephalosporins.

Amino Acid Sequence↗
PubMed1996

Patterns of hematopoietic chimerism following bone marrow transplantation for childhood acute lymphoblastic leukemia from volunteer unrelated donors.

Hematopoietic chimerism was analyzed in serial bone marrow samples taken from 28 children following T-cell depleted unrelated donor bone marrow transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric status was determined by polymerase chain reaction (PCR) of simple tandem repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial samples were examined in 23 patients. Of these, two had evidence of complete donor engraftment at all times and eight showed stable low level mixed chimerism (MC) (<1% recipient hematopoiesis). All 10 of these patients remain in remission with a minimum follow-up of 24 months. By contrast, 13 patients demonstrated a progressive return of recipient hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of cytomegalovirus pneumonitis and seven remain in remission with a minimum follow-up of 24 months. Five children were excluded from serial analysis as two serial samples were not collected before either relapse (3) or graft rejection (2). We conclude that as with sibling transplants, ex vivo T depleted UD BMT in children with ALL is associated with a high incidence of MC. Stable donor engraftment and low level MC always correlated with continued remission. However, detection of a progressive return of recipient cells did not universally correlate with relapse, but highlighted those patients at greatest risk. Serial chimerism analysis by PCR of STRs provides a rapid and simple screening technique for the detection of relapse and the identification of patients with progressive MC who might benefit from detailed molecular analysis for minimal residual disease following matched volunteer UD BMT for childhood ALL.

Adolescent↗
PubMed1994

PCR assessment of bone marrow status in 'isolated' extramedullary relapse of childhood B-precursor acute lymphoblastic leukaemia.

Approximately one-third of first relapses of childhood ALL occur at an extramedullary site without morphological evidence of bone marrow disease. However, the high incidence of subsequent medullary relapse in these cases strongly suggests that leukaemia is present at submicroscopic levels at the time of 'isolated' relapse. PCR analysis of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements now allows detection of leukaemia at levels as low as 0.001%. We have therefore used this technique to reassess bone marrow status at morphologically isolated relapse in 13 children with B-lineage ALL (11 with off-treatment relapses, two on treatment). In 12 of these 13 patients marrow disease was detectable by PCR at the time of this relapse--in all cases at levels below the threshold of light microscopy. Where relapse occurred off-therapy this indicated re-emergence of disease. since MRD has never been detected by PCR at this stage in patients remaining in long-term remission. In both patients who relapsed on-therapy the level of MRD at the time of relapse represented an increase on that seen in their previous marrow sample. We conclude that re-emerging bone marrow disease can be detected in most cases of 'isolated' relapse when investigated by this highly sensitive technique. Our findings at a molecular level confirm a long-held clinical suspicion and indicate that full systemic re-induction as well as local therapy is obligatory for these children.

Adolescent↗