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Biomedical subjects

M A Lewis

Publications and source records attributed to M A Lewis.

At least 19 recordsLinked to original sources
PubMed2006

Diabetes mellitus following paediatric renal transplantation: a single centre experience.

BACKGROUND/AIMS: Post-transplant diabetes mellitus (PTDM) has a variably reported incidence of 4-41% among adults and children. We describe our recent experience of four children with PTDM in a paediatric renal transplantation centre. METHODS: We undertook a retrospective analysis of the glycaemic status of all paediatric patients undergoing renal transplantation at our centre in the 2-year study period. The clinical features and investigations of those who developed PTDM were further reviewed. RESULTS: Five episodes of PTDM occurred in 4/32 children. There was a variable onset and a wide range of symptoms. Investigations revealed a combination of insulinopenia with peripheral insulin resistance. Insulin therapy was required for variable durations with resolution of PTDM in four episodes. PTDM did not adversely affect the renal graft function. CONCLUSION: PTDM requires increased awareness among paediatric nephrologists and endocrinologists for early recognition and prompt effective intervention.

Adolescent↗
PubMed2006

An evaluation of the quality of commercially produced patient information leaflets.

AIM: A descriptive study was undertaken to assess the quality of a range of patient information leaflets produced by the British Dental Association. METHOD: Twenty-nine leaflets were assessed with regard to presentation, readability and quality. The topic areas covered included: treatment, self-care and disease related information. Presentation was evaluated with regard to layout, font size, typeface, use of illustrations, paper type and print colour. Readability was assessed using the Flesch reading grade and the SMOG reading grade. Quality was assessed using the DISCERN tool. FINDINGS: All leaflets scored quite well for readability, with the average SMOG Reading Grade Level being 9.10 (SD 0.80) and the average Flesch reading Grade Level being 6.18 (SD 0.83). There were, however, some areas of presentation that could be improved, specifically font size, illustration use and paper finish, which did not comply with the RNIB guidelines. Quality ratings using the DISCERN tool were low. In particular most leaflets scored poorly in setting out clear aims in the opening paragraph, in identifying sources and dates of information provided, and other sources of advice and support available. Few leaflets discussed the option of no treatment or how the treatment would affect overall quality of life. The role of shared decision making was rarely mentioned. CONCLUSION: Patient information leaflets produced commercially are of high production quality and good readability but tend not to be patient centred.

Health Education, Dental↗
PubMed2006

Potential role of natural enemies during tree range expansions following climate change.

Recent investigations have shown how chance, long-range dispersal events can allow tree populations to migrate rapidly in response to changes in climate. However, this apparent solution to Reid's paradox applies solely within the context of single species models, while the rapid migration rates seen in pollen records occurred within multispecies communities. Ecologists are therefore presented with a new challenge: reconciling the macroscopic dynamics of spread seen in the pollen record with the rules and interactions governing plant community assembly. A case that highlights this issue is the rapid spread of Beech during the Holocene into a landscape already dominated by a close competitor, Hemlock. In this study, we analyse a simple model of plant community assembly incorporating competition for space and dispersal dynamics, showing how, even when a species is capable of rapid migration into an empty landscape, the presence of an ecologically similar competitor causes Reid's paradox to re-emerge because of the dramatic slowing effect of competitive interactions on a species' rate of spread. We then show how the answer to the question of how tree species dispersed rapidly into occupied landscapes may lie in secondary interactions with host-specific pathogens and parasites. Inclusion of host-specific pathogens into the simple community assembly model illustrates how tree species undergoing range expansions can temporarily outstrip specialist predators, giving rise to a transient Jansen-Connell effect, in which the invader acts as temporary 'super-species' that spreads rapidly into communities already occupied by competitors at rates consistent with those observed in the paleo-record.

Ecosystem↗
PubMed2006

National survey of doses from CT in the UK: 2003.

A review of patient doses from CT examinations in the UK for 2003 has been conducted on the basis of data received from over a quarter of all UK scanners, of which 37% had multislice capability. Questionnaires were employed to collect scan details both for the standard protocols established at each scanner for 12 common types of CT examination on adults and children, and for samples of individual patients. This information was combined with published scanner-specific CT dose index (CTDI) coefficients to estimate values of the standard dose indices CTDI(w) and CTDI(vol) for each scan sequence. Knowledge of each scan length allowed assessment of the dose-length product (DLP) for each examination, from which effective doses were then estimated. When compared with a previous UK survey for 1991, wide variations were still apparent between CT centres in the doses for standard protocols. The mean UK doses for adult patients were in general lower by up to 50% than those for 1991, although doses were slightly higher for multislice (4+) (MSCT) relative to single slice (SSCT) scanners. Values of CTDI(vol) for MSCT were broadly similar to European survey data for 2001. The third quartile values of these dose distributions have been used to derive UK national reference doses for examinations on adults (separately for SSCT and MSCT) and children as initial tools for promoting patient protection. The survey has established the PREDICT (Patient Radiation Exposure and Dose in CT) database as a sustainable national resource for monitoring dose trends in CT through the ongoing collation of further survey data.

Adult↗
PubMed2005

Hormone replacement therapy: pathobiological aspects of hormone-sensitive cancers in women relevant to epidemiological studies on HRT: a mini-review.

Hormone replacement therapy (HRT) has gained widespread and in some areas indiscriminate use. In reference to recent epidemiological studies which showed unexpected and controversial associations of HRT use with malignant tumours, here we review the current understanding of the dynamics of tumour growth. The pathomorphological characteristics and sex hormone sensitivity of cancers of the breast, endometrium, ovary and colon are discussed. The development of cancer from the first malignant tumour cell to clinical diagnosis takes many years. Hormones can influence tumour growth, but it is questionable whether hormones induce malignant tumours de novo. It is much more likely that hormones 'merely' promote the growth of already existing tumour cells. The long developmental process of tumours is in apparent contradiction to results of some epidemiological studies that describe an increased cancer risk, implying primary initiation, in HRT users within observation periods of 1-6 years. The mechanisms of initiation versus promotion of hormone-sensitive cancers, particularly breast cancer, are only partly understood. The conventional methods of epidemiological studies cannot detect potential risk factors without bias if they do not include a pathomorphological component on growth characteristics. The results of previous studies should be interpreted with great caution with regard to tumour biology.

Estrogen Replacement Therapy↗
PubMed2005

Persistence, spread and the drift paradox.

We derive conditions for persistence and spread of a population where individuals are either immobile or dispersing by advection and diffusion through a one-dimensional medium with a unidirectional flow. Reproduction occurs only in the stationary phase. Examples of such systems are found in rivers and streams, marine currents, and areas with prevalent wind direction. In streams, a long-standing question, dubbed 'the drift paradox', asks why aquatic insects faced with downstream drift are able to persist in upper stream reaches. For our two-phase model, persistence of the population is guaranteed if, at low population densities, the local growth rate of the stationary component of the population exceeds the rate of entry of individuals into the drift. Otherwise the persistence condition involves all the model parameters, and persistence requires a critical (minimum) domain size. We calculate the rate at which invasion fronts propagate up- and downstream, and show that persistence and ability to spread are closely connected: if the population cannot advance upstream against the flow, it also cannot persist on any finite spatial domain. By studying two limiting cases of our model, we show that residence in the immobile state always enhances population persistence. We use our findings to evaluate a number of mechanisms previously proposed in the ecological literature as resolutions of the drift paradox.

Models, Theoretical↗
PubMed2005

How parasitism affects critical patch-size in a host-parasitoid model: application to the forest tent caterpillar.

Habitat structure has broad impacts on many biological systems. In particular, habitat fragmentation can increase the probability of species extinction and on the other hand it can lead to population outbreaks in response to a decline in natural enemies. An extreme consequence of fragmentation is the isolation of small regions of suitable habitat surrounded by a large region of hostile matrix. This scenario can be interpreted as a critical patch-size problem, well studied in a continuous time framework, but relatively new to discrete time models. In this paper we present an integrodifference host-parasitoid model, discrete in time and continuous in space, to study how the critical habitat-size necessary for parasitoid survival changes in response to parasitoid life history traits, such as emergence time. We show that early emerging parasitoids may be able to persist in smaller habitats than late emerging species. The model predicts that these early emerging parasitoids lead to more severe host outbreaks. We hypothesise that promoting efficient late emerging parasitoids may be key in reducing outbreak severity, an approach requiring large continuous regions of suitable habitat. We parameterise the model for the host species of the forest tent caterpillar Malacosoma disstria Hbn., a pest insect for which fragmented landscape increases the severity of outbreaks. This host is known to have several parasitoids, due to paucity of data and as a first step in the modelling we consider a single generic parasitoid. The model findings are related to observations of the forest tent caterpillar offering insight into this host-parasitoid response to habitat structure.

Animals↗
PubMed2005

Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors.

Glycogen storage disease type II (GSDII) is caused by a lack of functional lysosomal acid alpha-glucosidase (GAA). Affected individuals store glycogen in lysosomes beginning during gestation, ultimately resulting in fatal hypertrophic cardiomyopathy and respiratory failure. We have assessed the utility of recombinant adeno-associated virus (rAAV) vectors to restore GAA activity in vivo in a mouse model of GSDII (Gaa(-/-)). A single systemic administration of a rAAV serotype 1 (rAAV1) vector to neonate animals resulted in restored cardiac GAA activity to 6.4 times the normal level (mean=641+/-190% of normal (Gaa(+/+)) levels with concomitant glycogen clearance) at 11 months postinjection. Greater than 20% of normal levels of GAA activity were also observed in the diaphragm and quadriceps muscles. Furthermore, functional correction of the soleus skeletal muscle was also observed compared to age-matched untreated Gaa(-/-) control animals. These results demonstrate that rAAV1 vectors can mediate sustained therapeutic levels of correction of both skeletal and cardiac muscles in a model of fatal cardiomyopathy and muscular dystrophy.

Animals↗
PubMed2004

Climate and competition: the effect of moving range boundaries on habitat invasibility.

Predictions for climate change include movement of temperature isoclines up to 1000 m/year, and this is supported by recent empirical studies. This paper considers effects of a rapidly changing environment on competitive outcomes between species. The model is formulated as a system of nonlinear partial differential equations in a moving domain. Terms in the equations describe competition interactions and random movement by individuals. Here the critical patch size and travelling wave speed for each species, calculated in the absence of competition and in a stationary habitat, play a role in determining the outcome of the process with competition and in a moving habitat. We demonstrate how habitat movement, coupled with edge effects, can open up a new niche for invaders that would be otherwise excluded.

Animals↗
PubMed2003

A fully coupled binary biochemical reactive-diffusion model with analytic solution.

Coupled multicomponent biochemical reactive diffusion underlies a variety of biological signalling processes and pharmacokinetic applications, such as paracrine signalling involving "cocktails" comprised of growth promoter/inhibitor factors and proteases associated with tumor angiogenesis, invasion and metastasis, extravascular drug delivery, and polymeric controlled-release drug codelivery design. Here, we present a model and develop a new analytic solution to illustrate the spatiotemporal behavior associated with fully coupled binary biochemical reactive diffusion. The complete coupling renders the solution appreciably more complex in structure and behavior than solutions for unicomponent or partially coupled models. Concentration behavior is illustrated by the computational simulation of binary-species tumor angiogenesis factor reactive-diffusion in the extravascular tissue matrix. The computational results indicate that (a) steady-state concentration profiles are achieved within 1 h of a change in factor production; (b) in the steady state, the spatial profiles of the two components tend to be similar; (c) exceedingly steep concentration gradients, involving several orders-of-magnitude differences in concentration over a few tenths of a millimeter, can occur in the vicinity of boundary sources due to inter-species reaction; (d) the concentration profiles of the two species differ from unicomponent predictions due to the simultaneous mass interchange between the two species. The analytic solution predictions are also used to provide a first-ever validation of a time-dependent, binary-component Crank-Nicholson numerical solution. The ability to quantitatively model interacting and often strongly varying concentration levels as a function of time and position can serve as a powerful complementary tool to experimental analyses for assessing disease state and interventional pharmacological efficacy, especially when the spatial scales on which in vivo behavior occurs taxes the limits of imaging capabilities.

Angiogenesis Inducing Agents↗
PubMed2002

An evaluation of the use of colonized periphyton as an indicator of wastewater impact in near-coastal areas of the Gulf of Mexico.

Receiving water impacts of point source discharges to the Gulf of Mexico are seldom reported on indigenous flora. The objective of this research was to evaluate the ability of colonized periphyton to provide this information. Water quality and biomass and pigment concentrations of the periphyton were determined at 27 stations located above and below 8 wastewater discharges. Most physicochemical parameters and concentrations of pesticides and PCBs were either unchanged or below detection in the receiving waters, which contrasted occasional increases in concentrations of several trace metals and nutrients. The response of the periphyton was specific to the wastewater, colonization station, response parameter, and colonization period. Statistically significant differences in biomass and pigment content occurred for at least one colonization station located below each of the eight outfalls. This represented a total of 18 of the 21 stations located in wastewater-impacted areas. Phytostimulation was more common than inhibition. Ash-free dry weight increased, on average, by 181% (+/- 1 SD = 123%) and chlorophyll a increased by 356% (+/- 593%) in wastewater-impacted areas. The in situ phytostimulation paralleled the stimulatory trend observed in standardized NPDES whole effluent tests conducted with cultured microalgae for four of eight wastewaters. The use of colonized periphyton as an indicator of wastewater impact was not simple. Spatial variation in response needs consideration to ensure relevancy of the results if this assessment methodology is used for near-coastal wastewater hazard evaluations.

Biomass↗
PubMed2001

Oral submucous fibrosis in a 11-year-old Bangladeshi girl living in the United Kingdom.

A case of oral submucous fibrosis occurring in a 11-year-old Bangladeshi girl is presented. This paper reviews the aetiology, clinical presentation and treatment modalities of oral submucous fibrosis. This case highlights the link between oral submucous fibrosis and the regular use of areca-nut (paan) and the newer transcultural oral tobacco products. This association has been reported among children resident in the Indian sub-continent but is unrecorded for United Kingdom residents. The case report underlines the danger that children face with products which are clearly targeted at them by the tobacco industry.

Areca↗
PubMed2001

ESS analysis of mechanistic models for territoriality: the value of scent marks in spatial resource partitioning.

In this paper elements of game theory are used to analyse a spatially explicit home range model for interacting wolf packs. The model consists of a system of nonlinear partial differential equations whose parameters reflect the movement behavior of individuals within each pack and whose solutions describe the patterns of space-use by each pack. By modifying the behavioral parameters, packs adjust their patterns of movement so as to maximize their reproductive output. This involves a tradeoff between maximizing prey intake and minimizing conflict with neighbors. Evolutionarily stable choices of the behavioral parameters yields territories that are immune to invasion by groups with alternate behaviors.

Animals↗
PubMed2001

Alpha(2) adrenoceptor agonists as potential analgesic agents. 3. Imidazolylmethylthiophenes.

A series of imidazolylmethylthiophenes has been prepared and evaluated as ligands for the alpha(2) adrenoceptor. These compounds were tested in two animal models that are predictive of analgesic activity in humans. The 3-thienyl compounds were generally the most potent, particularly those with substitution in the 4-position. A subset of the most active compounds was further evaluated for adverse cardiovascular effects in the anesthetized rat model. In addition to excellent binding at the alpha(2D) adrenoceptor, the 4-bromo analogues 20e and 21e were very active in the rat abdominal irritant test (RAIT) with ED(50) doses of 0.38 and 0.31 mg/kg, respectively. We constructed a pharmacophore model based on the biological activity of the present series, dexmedetomidine (1), and conformationally restrained analogues 3 and 4.

Adrenergic alpha-Agonists↗
PubMed2001

How predation can slow, stop or reverse a prey invasion.

Observations on Mount St Helens indicate that the spread of recolonizing lupin plants has been slowed due to the presence of insect herbivores and it is possible that the spread of lupins could be reversed in the future by intense insect herbivory [Fagan, W. F. and J. Bishop (2000). Trophic interactions during primary sucession: herbivores slow a plant reinvasion at Mount St. Helens. Amer. Nat. 155, 238-251]. In this paper we investigate mechanisms by which herbivory can contain the spatial spread of recolonizing plants. Our approach is to analyse a series of predator-prey reaction-diffusion models and spatially coupled ordinary differential equation models to derive conditions under which predation pressure can slow, stall or reverse a spatial invasion of prey. We focus on models where prey disperse more slowly than predators. We comment on the types of functional response which give such solutions, and the circumstances under which the models are appropriate.

Animals↗
PubMed2001

The relevance of rooted vascular plants as indicators of estuarine sediment quality.

Toxicity assessments and numerical quality assessment guidelines for estuarine sediments are rarely based on information for aquatic plants. The effect of this lack of information on contaminated sediment toxicity evaluations is largely unknown. For this reason, the toxicities of whole sediments collected from 15 sites in three urbanized Florida bayou-estuaries were determined for the benthic invertebrates Mysidopsis bahia and Ampelisca abdita and the plants Scirpus robustus Pursh (saltmarsh bulrush) and Spartina alterniflora Loisel (saltmarsh cordgrass). The results of the bioassays, conducted for 7 to 28 days, were compared for interspecific differences and to effects-based, sediment quality assessment guidelines. A variety of inorganic and organic analytes were detected in the estuarine sediments, and concentrations of as many as 7 analytes exceeded the sediment guidelines at the 15 sampling locations. Toxicity occurred at 2 of the 15 sampling stations based on invertebrate survival. Twelve of the 15 sediments had either a significant stimulatory or inhibitory effect on early seedling growth relative to a reference sediment (p < 0.05). The phytoresponse was specific to the location, test species, and plant tissue. There was no consistent trend between the sensitivities of the plants and invertebrates exposed to the sediments collected from the same sites. Of the 12 sediments that significantly affected seedling growth, 10 were not acutely toxic to the invertebrates. Consequently, the plant test species provided information that would have been missing if only animal test species were used. For this reason, the phytotoxicity database needs to be expanded for contaminated sediments to further evaluate interspecific sensitivities and to provide perspective on the environmental relevancy of proposed sediment quality criteria and effects-based assessment guidelines for which this information is usually missing. However, additional test method development and field validation are needed to support this effort, which includes the identification of sensitive plant test species, response parameters, and the chemical and physical sediment factors that influence plant growth.

Animals↗