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Biomedical subjects

J Miles

Publications and source records attributed to J Miles.

At least 19 recordsLinked to original sources
PubMed2026

First UK use of bacteriophage therapy with DAIR for chronic Staphylococcus aureus prosthetic joint infection.

BACKGROUND: Chronic Staphylococcus aureus prosthetic joint infection (PJI) remains difficult to manage when surgical revision and long-term antibiotics are not feasible. Bacteriophage therapy is emerging as a potential adjunct, though experience in orthopedic infections, particularly in the United Kingdom, is limited. CASE SUMMARY: We report the first UK case of intra-articular bacteriophage therapy administered alongside debridement, antibiotics, and implant retention (DAIR) for chronic methicillin-sensitive Staphylococcus aureus knee PJI. An 81-year-old man with multiple comorbidities developed persistent infection following revision knee arthroplasty, with recurrent sinus formation despite multiple surgical washouts and prolonged suppressive antibiotics. Major revision surgery and amputation were not viable options. Following a multidisciplinary review through the UK Clinical Phage Network, targeted phage therapy was pursued as salvage treatment. Phage susceptibility testing identified an active lytic phage (ISP). The patient underwent open DAIR with intra-articular phage administration, adjunctive local antibiotics, short-course intravenous antimicrobials, and subsequent oral suppressive therapy. Two further intra-articular phage doses were administered postoperatively. Initial sinus closure occurred, but recurrence developed within 4 weeks. At 18 months, symptoms were partially improved with better mobility and reduced inflammation, though one sinus tract persisted. No significant adverse effects were observed. Whole-genome sequencing of pretreatment isolates demonstrated a predominantly ST5 S. aureus genotype with conserved biofilm-associated virulence genes and limited antimicrobial resistance in addition to clonal diversification consistent with chronic biofilm infection. CONCLUSION: This case demonstrates the feasibility and safety of intra-articular phage therapy during DAIR in a UK setting but highlights biological, logistical, and pharmacological factors that may limit efficacy in advanced chronic PJI.

Staphylococcus aureus↗
PubMed2006

Hippocampal volume is as variable in young as in older adults: implications for the notion of hippocampal atrophy in humans.

Previous studies in humans have shown the presence of an age-related reduction of hippocampal (HC) volume, as well as the presence of reduced HC volume in psychiatric populations suffering from schizophrenia, depression or post-traumatic stress disorder. Altogether, these data suggested that aging or psychiatric disease can have neurotoxic effects on the hippocampus, and lead to HC atrophy. However, these two sets of findings imply that HC volume in young healthy adults should present less variability than HC volume in older adults and psychiatric populations. In the present study, we assessed HC volume in 177 healthy men and women aged from 18 to 85 years of age. We show that the dispersion around the mean of HC volume is not different in young and older adults, so that 25% of young healthy adults present HC volume as small as the average participants aged 60 to 75 years. This shows that HC volume is as variable in young as in older adults and suggests that smaller HC volume attributed to the aging process in previous studies could in fact represent HC volume determined early in life. We also report that within similar age groups, the percentage of difference in HC volume between the individuals with the smallest HC volume (smallest quartile) and the group average is greater than the percentage of difference reported to exist between psychiatric populations and normal control in recent meta-analyses. Taken together, these results confront the notion of hippocampal atrophy in humans and raise the possibility that pre-determined inter-individual differences in HC volume in humans may determine the vulnerability for age-related cognitive impairments or psychopathology throughout the lifetime.

Adolescent↗
PubMed2005

Outcome predictors and complications in the management of intradural spinal tumours.

The results of the management of 115 patients with intradural spinal tumours are presented. Data was collected retrospectively from the case notes. Tumours were categorized as intramedullary or extramedullary for statistical analysis. Meningioma, schwannoma and ependymoma accounted for 70% of tumours. Complete macroscopic excision was achieved in 84% of extramedullary and 54% of intramedullary tumours. There were two post-operative deaths, one of which was secondary to methacillin-resistant staphylococcus aureus (MRSA) meningitis. Cerebrospinal fluid leak (10%) and meningitis (7%) were the commonest complications. Ninety-six percent of patients with extramedullary tumours improved or remained unchanged on the Frankel scale. In the intramedullary group, 82% remained unchanged or improved after treatment. Pre-operative functional status was a predictor of good post-operative function for intra- and extramedullary tumours and for intramedullary tumours a good post-operative Frankel score predicted long-term survival.

Adolescent↗
PubMed2005

Primary antibody deficiency and diagnostic delay.

AIMS: To assess the occurrence of diagnostic delay in primary antibody deficiency in the period 1989-2002, since a similar study in 1989, and to assess the impact of UK national guidelines communicated in 1995. METHODS: A retrospective case note review was performed of 89 consecutive patients with antibody deficiency referred to a regional referral centre for clinical immunology in north west England and north Wales. The delay in diagnosis and the estimated resulting morbidity in terms of infections were assessed. RESULTS: Fifty six of the 89 patients experienced delay in diagnosis. The overall median delay was 2 years (mean, 4.4), resulting in substantial morbidity (equivalent to two major infections and one minor infection). This shows a moderate improvement since the previous study in 1989 and since the introduction of UK national guidelines in 1995. Respiratory infections are the most frequent presenting infections, and respiratory physicians the most common source of referral. CONCLUSIONS: There is still considerable delay in the diagnosis of primary antibody deficiency, but the data suggest an improvement in practice since the previous study in 1989 and the distribution of national guidelines in 1995.

Adolescent↗
PubMed2004

Antibody response to pneumolysin and to pneumococcal capsular polysaccharide in healthy individuals and Streptococcus pneumoniae infected patients.

BACKGROUND: Animal experiments have shown that antibodies against capsular polysaccharide enhance phagocytosis of pneumococcal bacteria and that antibodies against pneumolysin are anti-inflammatory and prevent pneumococcal invasion. It is not known if an antibody response to pneumolysin can be acquired from natural exposure to pneumococcal bacteria or how the concentration of pneumolysin antibody at the mucosal surface compares with that of antibodies against pneumococcal capsular polysaccharide. This study used an equal potency method to measure specific antibody concentrations against pneumolysin and pneumococcal capsular polysaccharides in order to facilitate comparative estimates of concentrations in saliva and serum. The results may provide experimental information as a basis for an improved pneumococcal vaccine strategy. RESULTS: Healthy individuals had higher IgM and IgG antibody concentrations against capsular polysaccharide than against pneumolysin in both saliva and serum, but for IgA the converse was true. Patients with acute pneumococcal infection had significantly lower concentrations of specific IgG antibodies against both antigens than the healthy group. These patients also had significantly higher concentrations of IgM antibody against both antigens than the healthy control group. DISCUSSION: Healthy individuals acquire a comparatively lower concentration of antibody to pneumolysin than to pneumococcal capsular polysaccharides from natural exposure to pneumococcal bacteria. Patients infected by pneumococcal bacteria have lower specific IgG antibody concentrations to both antigens than healthy individuals. These findings support the view that pneumolysin could potentially be used as a vaccine. For enhanced effectiveness, it could be used as a supplement to Pneumovax((R))II rather than as a replacement. The two acquired antibodies, i.e. to pneumolysin and to capsular polysaccharide, could then play their protective roles at different stages in the course of pneumococcal infection, and together contribute to an effective immune defence against Streptococcus pneumoniae.

Adult↗
PubMed2004

Two dimensions of measurement error: classical and Berkson error in residential radon exposure assessment.

Measurement error in exposure assessment is unavoidable. Statistical methods to correct for such errors rely upon a valid error model, particularly regarding the classification of classical and Berkson error, the structure and the size of the error. We provide a detailed list of sources of error in residential radon exposure assessment, stressing the importance of (a) the differentiation between classical and Berkson error and (b) the clear definitions of predictors and operationally defined predictors using the example of two German case-control studies on lung cancer and residential radon exposure. We give intuitive measures of error size and present evidence on both the error size and the multiplicative structure of the error from three data sets with repeated measurements of radon concentration. We conclude that modern exposure assessment should not only aim to be as accurate and precise as possible, but should also provide a model of the remaining measurement errors with clear differentiation of classical and Berkson components.

Bias↗
PubMed2004

Use of sensorineural tests in a large volume of medico-legal compensation claims for HAVS.

BACKGROUND: The Department of Trade and Industry set up a contract to examine miners and ex-miners claiming compensation for hand-arm vibration syndrome (HAVS). They had been exposed to hand-transmitted vibration. Over 100,000 have now been examined using sensorineural tests as part of that process. AIMS: The purpose of this paper was to examine the internal consistency of the vibrotactile threshold test (VTT) and the thermal aesthesiometry test (TA). METHODS: In 18 centres across the UK, nurses were trained to perform the measurement of VTT and TA in a controlled standardized manner. These tests were to aid the staging of the neurological component of the Stockholm Workshop Scales. The staging of this component was modified by dividing stage 2SN into 2SN (early) and 2SN (late). The test results and an automatic neurological staging were presented to the examining doctor following the clinical examination. The results of these sensorineural tests were held on a central database. The results and analysis of the first 57,000 tests are reported. RESULTS: The correlations within the VTT and TA scores were consistent with reliable measures. However, these correlations were not of such strength as to allow reliance on the results of a single test when making an assessment of the severity of neurological damage. CONCLUSIONS: Different end organs and nerve fibres should be tested when making an assessment of damage in the sensorineural component of HAVS. The correlations demonstrated for the VTT and TA suggest that they are of value in assessing these claimants and would be for other vibration exposed workers.

Arm↗
PubMed2003

Extracorporeal shock-wave treatment for tennis elbow. A randomised double-blind study.

The efficacy of extracorporeal shock-wave therapy for tennis elbow was investigated using a single fractionated dosage in a randomised, double-blind study. Outcomes were assessed using the Disabilities of Arm, Shoulder and Hand questionnaire, measurements of grip strength, levels of pain, analgesic usage and the rate of progression to surgery. Informed consent was obtained before patients were randomised to either the treatment or placebo group. In the final assessment, 74 patients (31 men and 43 women) with a mean age of 43.4 years (35 to 71), were included. None of the outcome measures showed a statistically significant difference between the treatment and control groups (p > 0.05). All patients improved significantly over time, regardless of treatment. Our study showed no evidence that extracorporeal shock-wave therapy for tennis elbow is better than placebo.

Adult↗
PubMed2002

Effect of Pneumovax II vaccination in high-risk individuals on specific antibody and opsonic capacity against specific and non-specific antigen.

Pneumovax II vaccine has been used in many countries including the UK for adults in high-risk groups to prevent pneumococcal infections. However, its effectiveness has been a controversial issue. In this study, the specific antibody concentration and opsonic capacity of serum against specific and non-specific antigens were measured in 16 high-risk adults vaccinated with Pneumovax II. The results indicated that 38% of these individuals could make an antibody response to specific antigens post-vaccination; vaccination had a clear effect in increasing the opsonic capacity of serum against specific pneumococcal antigen (S14 serotype) in 31% of patients, but did not have any effect against non-specific antigen. The specific antibody concentration did not significantly positively correlate with the opsonic capacity of serum. Therefore, it is concluded that the protective effect of Pneumovax II vaccination against a specific serotype in high-risk individuals will only be around 30%.

Adult↗
PubMed2002

Assessing the burden of respiratory disease in the UK.

This review explores the health and social burden of some of the main respiratory diseases (asthma, chronic obstructive pulmonary disease, cryptogenic fibrosing alveolitis, cystic fibrosis, lung cancer, mesothelioma, obstructive sleep apnoea and tuberculosis) in order to increase awareness of these diseases and highlight areas where improvements in care are required. The overall impact of respiratory diseases in the U.K. in terms of prevalence, mortality, morbidity and economic costs, with particular reference to secondary care has been considered and comparisons made with the rest of Europe where data are available. Respiratory diseases are responsible for a significant proportion of serious morbidity and premature death among the population of the U.K. and they will continue to present a growing challenge; special support is needed to tackle this burden.

Adolescent↗
PubMed2002

Use of a model data set to test methods for mapping radon potential.

It is difficult to test the accuracy of mapping methods using real measurement data of radon levels in houses, as different methods produce different maps, and there is no standard to compare them with. A model data set, Linevar, was therefore constructed, having features which allow the accuracies of different mapping methods to be compared. Data for Linevar were generated such that they had a geometric mean that varied across the map in a pattern of stripes of higher and lower radon potential. with widths of 1, 2, 4, and 8 km over an area 100 km square. The geometric standard deviation was kept at a constant value. Data were generated at densities varying from 1 to 100 results per 1 km grid square in different parts of the map. The data set was used to develop a mapping method that shows as much detail as possible without generatin, artefacts.

England↗
PubMed2002

Limitations of Pneumovax as a detection antigen in the measurement of serotype-specific antibodies by enzyme-linked immunosorbent assay.

BACKGROUND: Measurement of antibody responses to polysaccharide antigens is regarded as an important assessment of an individual's ability to respond to carbohydrate antigens. The currently used assays for the measurement of pneumococcal-specific antibody use the multi-serotype vaccine Pneumovax as the detection antigen. METHODS: An equal potency enzyme-linked immunosorbent assay (ELISA) system was used to compare the measurement of serotype-specific antibody with the multi-serotype assay. RESULTS: Our results show that the concentration of specific antibody to Pneumovax is not related to the concentration of antibody to the individual serotypes. Neither is any correlation found between the antibody concentrations to any of the three single serotypes investigated, to the mixture of the three serotypes or to Pneumovax. CONCLUSION: We conclude that the measurement of the concentration of the specific antibody to the mixed serotypes present in Pneumovax has serious limitations when used to evaluate the protection acquired from Pneumovax immunization against any specific serotype.

Antibodies, Bacterial↗
PubMed2001

The LN54 radiation hybrid map of zebrafish expressed sequences.

To increase the density of a gene map of the zebrafish, Danio rerio, we have placed 3119 expressed sequence tags (ESTs) and cDNA sequences on the LN54 radiation hybrid (RH) panel. The ESTs and genes mapped here join 748 SSLp markers and 459 previously mapped genes and ESTs, bringing the total number of markers on the LN54 RH panel to 4226. Addition of these new markers brings the total LN54 map size to 14,372 cR, with 118 kb/cR. The distribution of ESTs according to linkage groups shows relatively little variation (minimum, 73; maximum, 201). This observation, combined with a relatively uniform size for zebrafish chromosomes, as previously indicated by karyotyping, indicates that there are no especially gene-rich or gene-poor chromosomes in this species. We developed an algorithm to provide a semiautomatic method for the selection of additional framework markers for the LN54 map. This algorithm increased the total number of framework markers to 1150 and permitted the mapping of a high percentage of sequences that could not be placed on a previous version of the LN54 map. The increased concentration of expressed sequences on the LN54 map of the zebrafish genome will facilitate the molecular characterization of mutations in this species.

Animals↗
PubMed2001

Intrathoracic lipoma in a Labrador retriever.

Pyrexia, granulocytosis and hyperglobulinaemia were the main clinical findings in an unusual case of intrathoracic lipoma in a 12-year-old male Labrador retriever. The response to antibiotic and anti-inflammatory treatment was poor, prompting further investigation. Survey radiographs and ultrasonography revealed a cavitated, fluid-filled soft tissue mass in the right hemithorax, which was successfully removed resulting in rapid resolution of clinical signs. Lipomas are rare intrathoracic extrapulmonary tumours. Previously reported clinical signs are dyspnoea and coughing, attributed to the mass effect of the lipoma. The unusual presentation in this case was caused by necrosis of the lipoma, probably owing to torsion of the pedicle attaching it to the cranial mediastinum.

Animals↗
PubMed2001

Intrathecal therapy for chronic pain.

With the improved utilisation and widespread availability of opiates, the oral treatment of pain due to malignancy has changed radically, so that the expected need for intrathecal (IT) delivery systems for this pain has largely failed to materialise. Instead, the lack of equal progress in the design and production of non-opiates for treating non-malignant pain, in the long term, has resulted in a greater interest in the development of these IT systems in this non-malignant area.

Administration, Oral↗
PubMed2001

Intrathecal treatment for spasticity.

Although initially to be treated by oral spasmolytics, established spasticity is being increasingly recognised as needing direct pharmacotherapy to the spinal cord by the intrathecal route using drug delivery systems. Although the spasticity is mainly of spinal origin due to trauma or multiple sclerosis (M.S.), it can emanate from the brain as in cerebral palsy in children and require the same direct treatment. Drug delivery systems are now proven to be safe, clinically reliable, and cost effective and should be considered earlier in the disease process.

Drug Delivery Systems↗
PubMed2001

An instrument to measure musculoskeletal symptoms among immigrant Hispanic farmworkers: validation in the nursery industry.

We report on the construction and psychometrics of a survey measure of musculoskeletal symptomatology for use with Spanish-speaking immigrant farmworkers. Survey development included focus groups with workers, forward and backward translations, and pilot testing. The final survey includes a body diagram and items about symptom severity, frequency, and duration and about self-treatment, medical care, and job tasks. We report on the initial test of the survey with 213 commercial nursery workers in Southern California. Fifty-five percent of the workers reported pain, with 30% reporting back pain, 21% reporting upper extremity pain, 19% reporting lower extremity pain, and 10% reporting neck and shoulder pain. A composite symptom score exhibited acceptable test-retest reliability (r = 0.41, p < 0.01) over the annual agricultural cycle. Greater symptomatology was associated with greater frequency of self-treatment (r = 0.42, p < 0.01), seeking professional health care (t = 2.49, p < 0.05), and exposure to high-risk jobs (OR = 2.1, p < 0.05, CI = 1.0 to 4.4), supporting the validity of composite score.

Adolescent↗