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Biomedical subjects

M Morgan

Publications and source records attributed to M Morgan.

At least 19 recordsLinked to original sources
PubMed2006

A prospective comparison of multidisciplinary treatment of oesophageal cancer with curative intent in a UK cancer network.

AIMS: Combined modality therapy (with chemotherapy+/-radiotherapy) has become a standard treatment for locally advanced oesophageal cancer. However, there appears to be no compelling evidence for one treatment type or combination to suit all and at this time the clinical multi-disciplinary team (MDT) forms an important role in selecting optimal therapies for the individual. This prospective comparison in one cancer network, looks at the outcomes of this decision making process. METHODS: Over a five year period 1998-2003, data were prospectively collected on all 330 consecutive patients, referred to a tertiary specialised MDT for whom curative treatment was the planned intent. Patients were managed according to an agreed local protocol and allocated to receive one of 5 treatments: surgery alone (S), pre-operative chemotherapy (C+S), pre-operative chemo-radiotherapy (CRT+S), definitive chemo-radiotherapy (CRT) and radiotherapy alone (RT). RESULTS: The 2 and 5 year survival for all patients receiving potentially curative treatment were 49% and 26% respectively. With 2 and 5 year survival for S, CRT+S, C+S, CRT and RT being 53,21; 57,40; 37,27; 50,27; 23,0 months respectively. Of the surgical therapies, mortality was highest in the CRT+S group, versus C+S and S; 12.5%, 1.6%, 4.5% respectively (p=0.025). Non-surgical based therapies had more than double the incidence of local relapses compared to surgical based therapies; however the CRT group had an overall survival comparable with S alone. The commonest sites of distant relapse were liver (56%), lung (38%), bone (32%) and non-regional lymph nodes (24%). CONCLUSION: The results suggest that in patients who are deemed unfit for surgical intervention, definitive chemoradiotherapy remains a viable alternative; they also lend further support to selected case triple modality therapy. These areas should be further examined in the context of randomised controlled phase III trials.

Aged↗
PubMed2006

Instantaneous effects of resynchronisation therapy on exercise performance in heart failure patients: the mechanistic role and predictive power of total isovolumic time.

BACKGROUND: Cardiac resynchronisation therapy improves peak oxygen uptake (peak VO(2)) 3-9 months after device implantation. In chronic heart failure, total isovolumic time (t-IVT) is a major determinant of peak VO(2) and of cardiac output at peak dobutamine stress. In selected patients, resynchronisation can instantaneously shorten t-IVT. We sought to determine the acute effect of resynchronisation on exercise performance and determine, with pharmacological stress echocardiography, the mechanism underlying this effect. METHODS AND RESULTS: Twenty-two patients with resynchronisation were studied within 3 months after device implantation. On a single study day, sequential cardiopulmonary exercise tests were performed during native activation (left bundle branch block) and resynchronisation (atrio-biventricular pacing) in random order. Total-IVT and cardiac output (at rest and peak dobutamine stress) were then measured in each activation mode. Resynchronisation acutely increased peak VO(2) by 1.6 (SD 1.5) ml/kg/min (p<0.001) and shortened peak stress t-IVT by 10 (SD 7) s/min (p<0.001), with the effects in individual patients showing a correlation (r = -0.46, p<0.05). Amongst all measurements during native activation, the best predictor of gain in peak VO(2) from resynchronisation was peak stress t-IVT (r = 0.71, p<0.001) with every increment of 5 s/min of peak stress t-IVT during native activation predicting an 8% gain in peak VO(2). No conventional measures during native activation at rest or on stress (including QRS duration, Tei index, tissue Doppler intraventricular delay, and resting t-IVT) added significant additional information. CONCLUSIONS: In eligible patients, resynchronisation can acutely augment peak VO(2), possibly through a mechanism of t-IVT shortening. Under native activation, long t-IVT during peak stress is the single best predictor of acute resynchronisation-mediated increment in peak VO(2).

Aged↗
PubMed2006

Predicting the motion after-effect from sensitivity loss.

The widely accepted disinhibition theory of the motion after-effect (MAE) proposes that the balance point of an opponent mechanism is changed by directional adaptation. To see if the post-adaptation balance point could be predicted from contrast adaptation, we measured threshold-vs-contrast (i.e., T-vs-C or dipper) functions, before and after adaptation to moving gratings. For test stimuli moving in the same direction, adaptation shifted the point of maximum facilitation (i.e., the dip) upwards and rightwards. For tests moving in the opposite direction, adaptation produced a similar, but smaller, shift. These shifts are consistent with a change in divisive gain control. They are also consistent with subtractive inhibition followed by half-wave rectification. We attempted to use transducer functions derived from these data to predict the strength of the MAE. When combined, gratings moving in the adapted and opposite directions appeared perfectly balanced (i.e., counterphasing) when the latter was given approximately 2% more contrast than was predicted on the basis of the derived transducers. This small under-prediction may be indicative of sensory recalibration. Finally, we found that adaptation did not alter the fact that low-contrast stimuli could be detected and their direction identified with similar accuracy. We conclude that both static and dynamic forms of MAE are primarily caused by a decreased sensitivity in directionally tuned mechanisms, as proposed by the disinhibition theory.

Adaptation, Biological↗
PubMed2006

Phosphodiesterase (PDE) 7 in inflammatory cells from patients with asthma and COPD.

In inflammatory cells, the low K(m) cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase (PDE) 4 subtype is predominant in terms of expression and function, although more recently it has been suggested that PDE 7 may also play a role in regulating inflammatory cell activity. In the present study, PDE 4 and PDE 7 subtype messenger ribonucleic acid (mRNA) transcripts in CD4 and CD8 lymphocytes from healthy (n=10) and asthmatic (n=10) subjects and polymorphonuclear neutrophils (PMNs) and CD8 lymphocytes obtained from healthy (n=10) and chronic obstructive pulmonary disease (COPD) (n=7) subjects were identified and quantified. PDE 4A, PDE 4B, PDE 4D and PDE 7A mRNA were present in similar quantities in both CD4 and CD8 lymphocytes obtained from healthy and asthmatic subjects and in CD8 lymphocytes obtained from healthy and COPD subjects. Expression of PDE 4C and PDE 7B mRNA was also observed, although transcript levels were low and variable between individuals. In addition, the effects of selective PDE 7 inhibition on both phytohaemagluttinin (PHA)-induced human peripheral blood mixed mononuclear cell (HPBMNC) proliferation and fMLP-induced neutrophil elastase (NE) release were studied. HPBMNC and human neutrophils, isolated from the venous blood of healthy volunteers (n=6) were treated with either a novel selective PDE 7 inhibitor PF 0332040 alone or in combination with rolipram. Proliferation of HPBMNC was stimulated by PHA (2microgml(-1)) and assessed by [(3)H]-thymidine incorporation, while fMLP-induced (100nM) NE release was determined using a chromogenic substrate. Both rolipram (0.003-10microM) and PF 0332040 (0.003-10microM) significantly inhibited PHA-stimulated proliferation of HPBMNC ((**)P<0.01). Co-administration of rolipram (0.3-10microM) and PF 0332040 (0.003-10microM) significantly increased the degree of inhibition observed, compared to when either drug was administered alone ((**)P<0.01). PF 0332040 (0.003-10microM) had no inhibitory effect on NE release from human peripheral blood neutrophils stimulated with fMLP (100nM), while rolipram (0.003-10microM) significantly inhibited neutrophil degranulation ((**)P<0.01). These findings suggest no evidence of altered PDE 4 or PDE 7 mRNA transcript levels in inflammatory cells isolated from the peripheral venous blood of mild asymptomatic asthmatic subjects or stable COPD subjects, however, inhibition of PDE 7 may influence mononuclear cell function.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Improved plausibility bounds about the 2005 HIV and AIDS estimates.

BACKGROUND: Since 1998 the Joint United Nations Programme on HIV/AIDS and the World Health Organization has provided estimates on the magnitude of the HIV epidemic for individual countries. Starting with the 2003 estimates, plausibility bounds about the estimates were also reported. The bounds are intended to serve as a guide as to what reasonable or plausible ranges are for the uncertainty in HIV incidence, prevalence, and mortality. METHODS: Plausibility bounds were developed for three situations: for countries with generalised epidemics, for countries with low level or concentrated epidemics (LLC), and for regions. The techniques used build on those developed for the previous reporting round. However the current bounds are based on the available surveillance and survey data from each individual country rather than on data from a few prototypical countries. RESULTS: The uncertainty around the HIV estimates depends on the quality of the surveillance system in the country. Countries with population based HIV seroprevalence surveys have the tightest plausibility bounds (average relative range about the adult HIV prevalence (ARR) of -18% to +19%.) Generalised epidemic countries without a survey have the next tightest ranges (average ARR of -46% to +59%). Those LLC countries which have conducted multiple surveys over time for HIV among the populations most at risk have the bounds similar to those in generalised epidemic countries (ARR -40% to +67%). As the number and quality of the studies in LLC countries goes down, the plausibility bounds increase (ARR of -38% to +102% for countries with medium quality data and ARR of -53% to +183% for countries with poor quality data). The plausibility bounds for regions directly reflect the bounds for the countries in those regions. CONCLUSIONS: Although scientific, the plausibility bounds do not represent and should not be interpreted as formal statistical confidence intervals. However in order to make the bounds as meaningful as possible the authors have tried to apply reasonable statistical approaches and assumptions to their derivation. An understanding of the uncertainty in the HIV estimates may help policy makers take better informed decisions to address the epidemic in their respective countries.

Adolescent↗
PubMed2005

Clinician-led surgical site infection surveillance of orthopaedic procedures: a UK multi-centre pilot study.

The UK Department of Health established the Healthcare-associated Infection (HAI) Surveillance Steering Group in 2000 to develop a strategy for implementing a national programme for HAI surveillance in National Health Service trusts. A subgroup of this committee examined the surveillance of surgical site infections following orthopaedic surgery. This group oversaw a pilot scheme that was set up in 12 hospitals around the UK to explore the feasibility of implementing a system of surveillance that engaged clinical staff in its operation, provided a process for continuous data collection and could be maintained as part of routine hospital operation over time. A minimum data set was established by the subgroup, and Centers for Disease Control and Prevention (CDC) definitions of infection were used. By March 2003, the surveillance had been undertaken continuously in 11 sites for one to two years, depending on the date of implementation. Only one hospital had ceased data collection. The information was collected mainly by clinical staff, with support and co-ordination usually provided by infection control teams. Data on more than 5400 procedures were available for analysis for four core procedures: arthroplasty of the hip and knee; hemi-arthroplasty of the hip; and internal fixation of trochanteric fractures of the femur. The data set permitted the calculation of risk-adjusted rates, allowing comparisons between hospitals and within a hospital over time. The methodology enhanced clinical ownership of the surveillance process, re-inforced infection control as the responsibility of all staff, and provided timely feedback and local data analysis. The use of CDC definitions permitted international comparisons of the data.

Adult↗
PubMed2005

Hospital management of animal and human bites.

The management of bites severe enough to warrant hospital admission is complex. This review includes the epidemiology, clinical management, investigations, microbiology and role of antimicrobials for all types of animal and human bites likely to be encountered in UK hospitals.

Adult↗
PubMed2005

Asymmetrical introgression between two Morus species (M. alba, M. rubra) that differ in abundance.

Asymmetrical introgression is an expected genetic consequence of hybridization when parental taxa differ in abundance; however, evidence for such effects in small populations is scarce. To test this prediction, we estimated the magnitude and direction of hybridization between red mulberry (Morus rubra L.), an endangered species in Canada, and the introduced and more abundant white mulberry (Morus alba L.) using nuclear (randomly amplified polymorphic DNA) and cytoplasmic (chloroplast DNA sequence) markers. Parentage of 184 trees (n = 42 using cpDNA) from four sympatric populations was estimated using a hybrid index and related to six morphological characters and population frequencies of the parental classes. Overall, the frequency of nuclear hybrids was 53.7% (n = 99) and ranged from 43% to 67% among populations. The parental and hybrid taxa differed with respect to all of the morphological traits. Sixty-seven percent of all hybrids contained more nuclear markers from M. alba than M. rubra (hybrid index x = 0.46); among populations, the degree of M. alba bias was correlated with the frequency of M. alba. In addition, the majority of hybrids (68%) contained the chloroplast genome of white mulberry. These results suggest that introgression is bidirectional but asymmetrical and is related, in part, to the relative frequency of parental taxa.

Analysis of Variance↗
PubMed2004

The differentiation profile of the epithelium of the human lip.

The aim of this study was to analyse the immunohistochemical differentiation profile of the stratified squamous epithelium of the adult human lip. Full-thickness lower lips taken from 31 cadavers were analysed. Sections were stained with haematoxylin and eosin, periodic acid-Schiff (PAS), cytokeratins (CK), loricrin, involucrin, profilaggrin and filaggrin. The stratified squamous epithelium covering the lip could be divided into: (i) appendage-bearing, orthokeratinised epidermis; (ii) orthokeratinised vermilion which had a more prominent rete pattern than the epidermis; (iii) parakeratinised, PAS-positive intermediate zone; and (iv) non- or parakeratinised labial mucosal epithelium. Epithelial thickness increased gradually from the skin to the mucosal aspect. The CK pattern changed across the intermediate zone, with gradual loss of CK 1 and 10 from the skin, and CK 4, 13 and 19 from the mucosal, aspect. CK 5 and 14 were consistently expressed basally, and variably expressed suprabasally. Apart from labelling Merkel cells, CK 8, 18 and 20 were negative. Involucrin, which was present at all sites, was restricted to the stratum granulosum in skin, but extended into the stratum spinosum, and gradually into parabasal keratinocytes, across the vermilion and mucosa. Loricrin, profilaggrin and filaggrin were present in the stratum granulosum of orthokeratinised sites, but expression was abruptly lost at the junction between the vermilion and the intermediate zone. In conclusion, the phenotype of the stratified squamous epithelium covering the lip changes at, or across, the intermediate zone of the adult vermilion. It is possible that changes in the composition of the stratified squamous epithelium affect the colour of the vermilion.

Adult↗
PubMed2004

Genetic epidemiology of Sarcoptes scabiei (Acari: Sarcoptidae) in northern Australia.

Utilising three hypervariable microsatellite markers we have previously shown that scabies mites on people are genetically distinct from those on dogs in sympatric populations in northern Australia. This had important ramifications on the formulation of public health control policies. In contrast phylogenetic analyses using mitochondrial markers on scabies mites infecting multiple animal hosts elsewhere in the world could not differentiate any genetic variation between mite haplotype and host species. Here we further analyse the intra-specific relationship of Sarcoptes scabiei var. hominis with S. scabiei var. canis by using both mitochondrial DNA and an expanded nuclear microsatellite marker system. Phylogenetic studies using sequences from the mitochondrial genes coding for 16S rRNA and Cytochrome Oxidase subunit I demonstrated significant relationships between S. scabiei MtDNA haplotypes, host species and geographical location. Multi-locus genotyping using 15 microsatellite markers substantiated previous data that gene flow between scabies mite populations on human and dog hosts is extremely rare in northern Australia. These data clearly support our previous contention that control programs for human scabies in endemic areas with sympatric S. scabiei var. hominis and var. canis populations must focus on human-to-human transmission. The genetic division of dog and human derived scabies mites also has important implications in vaccine and diagnostic test development as well as the emergence and monitoring of drug resistance in S. scabiei in northern Australia.

Animals↗
PubMed2004

Intraspinal lumbar synovial cysts: diagnosis and surgical management.

BACKGROUND: Lumbar synovial cysts are a common association of facet joint degenerative disease. However, it is relatively rare for these cysts to cause symptoms of radiculopathy and nerve root compression. PATIENTS AND METHODS: We report a series of eight cases which were treated over a period of 20 months. There were five female and three male patients with a mean age of 66 years, and an average follow-up of seventeen months. All patients had pre-operative flexion/extension radiographs and MRI scans. Two patients had failed non-surgical treatment, two were associated with a Grade 1 spondylolisthesis, and all were associated with facet joint arthropathy. There were five cases occurring at L4/5 and three at L5/S1. RESULTS: All patients underwent identical procedures, which involved exploration, hemi-laminotomy, flavectomy and minimal facet joint excision. No patient required posterior lumbar interbody fusion and at follow-up five patients had excellent and three had good results.

Aged↗
PubMed2004

The payment of drug addicts to increase their sterilisation rate is morally unjustified and not simply 'A Fine Balance'.

This paper argues that cash incentives offered to drug addicts in return for sterilisation are both legally and morally unacceptable. Such incentives act coercively, undermines one's freedom and autonomy and importantly invalidates real consent. This has important implications for any clinicians involved in such a scheme. The paper prompts more detailed studies into the use of incentives in modern-day health care.

Coercion↗
PubMed2004

Implementing the 2-week wait rule for cancer referral in the UK: general practitioners' views and practices.

The 2-week wait rule for cancer referrals became effective in December 2000 for all cancers treated by the National Health Service in the UK. Attainment of this target depends initially on appropriate and timely referral by general practitioners (GPs). General practitioners' views and referral practices under the 2-week wait rule were examined based on a postal survey of 508 GPs in an inner London area (65% response). Data on mode of referral indicated that 90% of GPs used the urgent suspected cancer form, although 38% also sent a letter with further information. General practitioners generally regarded the 2-week wait rule as working well in terms of improving patients' initial access, and 50% thought communication with the hospital had improved. However, 46% expressed some concerns, including problems arising from the different sets of forms required by local cancer networks, the lack of a dedicated referral form for breast cancer, and feelings of a loss of autonomy. General practitioners also acknowledged an element of over-referral under this rule due to the effects of clinical uncertainty and patient pressure and their concerns about increased waiting times for non-target referrals. The survey therefore indicates that GPs are generally positive about the 2-week wait rule but identified some problems of implementation including a need for standardized national cancer referral forms.

Attitude of Health Personnel↗
PubMed2004

Feasibility of using the TOSCA telescreening procedures for diabetic retinopathy.

AIMS: The TOSCA project was set up to establish a tele-ophthalmology service to screen for diabetic retinopathy (DR) in Europe. The aim of this study was to determine the feasibility of establishing telemedicine-based digital screening for detecting DR and to evaluate the satisfaction of both patients and healthcare professionals with the screening procedures used within the TOSCA project. METHODS: The study was a non-randomized, multicentre study carried out in four different countries over a period of 3 months. Patients (n = 390) with diabetes aged > 12 years were included. Two digital retinal images per eye (macular and nasal) were taken and exported to a central server. Patients were asked to complete a questionnaire to assess satisfaction. Accredited graders carried out grading remotely and the results were reported back to the referring centre. Previously graded patient data chosen randomly to represent examples of both DR and no DR were also sent anonymously to the grading centre at a frequency of approximately every 10 patients. RESULTS: Most (99%) of the images were assessable enabling a retinopathy grade to be assigned to the patient. Patients found the retinal photography procedures acceptable; only 6% in one centre would not recommend the procedure. Healthcare professionals (photographers and graders) were also satisfied with the overall procedures. The average time taken to grade each patient was approximately 5 min. CONCLUSIONS: This study demonstrated that it is feasible to electronically transmit and grade retinal images remotely using the TOSCA process. Built-in quality assurance procedures proved acceptable.

Adolescent↗
PubMed2004

Uncertainty in estimates of HIV/AIDS: the estimation and application of plausibility bounds.

OBJECTIVES: To establish the accuracy of the country specific estimates of HIV prevalence, incidence, and AIDS mortality published every 2 years by UNAIDS and WHO. METHODS: We review sources of error in the data used to generate national HIV/AIDS and where possible estimate their statistical properties. We use numerical and approximate analytic methods to estimate the combined impact of these errors on HIV/AIDS estimates. Heuristic rules are then derived to produce plausible bounds about these estimates for countries with different types of epidemic and different qualities of surveillance system. RESULTS: Although 95% confidence intervals (CIs) can be estimated for some sources of error, the sizes of other sources of error must be based on expert judgment. We therefore produce plausible bounds about HIV/AIDS estimates rather than statistical CIs. The magnitude of these bounds depends on the stage of the epidemic and the quality and coverage of the sentinel HIV surveillance system. The bounds for adult estimates are narrower than those for children, and those for prevalence are narrower than those for new infections. CONCLUSIONS: This paper presents a first attempt at a rigorous description of the errors associated with estimation of global statistics of an infectious disease. The proposed methods work well in countries with generalised epidemics (>1% adult HIV prevalence) where the quality of surveillance is good. Although methods have also been derived for countries with low level or concentrated epidemics, more data on the biases in the estimation process are required.

Acquired Immunodeficiency Syndrome↗