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Biomedical subjects

M Willis

Publications and source records attributed to M Willis.

At least 19 recordsLinked to original sources
PubMed2004

Image-guided robotic radiosurgery in a rat glioma model.

Despite the proven efficacy of radiosurgery for the treatment of brain tumors, limited histological information is available after treatment that might allow a better understanding of the relationship between radiation dose, the volume treated, and the response of the surrounding brain to the delivered radiation. The use of an animal model could provide the opportunity to clarify these relationships and answer several other key questions arising in clinical practice. We show here that treatment of small animals with radiosurgery is feasible using a robotically controlled linear accelerator, which offers the advantages of radiosurgery and preserves the potential for fractionated regimens without rigid immobilization. Specifically, we demonstrate the use of a robotically driven linear accelerator to provide radiosurgical treatment to a rat brain tumor model.

Animals↗
PubMed2002

Cost-effectiveness of treating deep diabetic foot ulcers with Promogran in four European countries.

OBJECTIVE: This study aimed to estimate the cost-effectiveness of treating non-superficial diabetic foot ulcers with Promogran plus good wound care (GWC) compared with GWC alone in four European countries (France, Germany, Switzerland and UK). METHODS: An existing Markov-based health economic model of non-superficial diabetic foot ulcers was adapted to incorporate the relative efficacy of Promogran compared with GWC alone as demonstrated in a randomised controlled trial. Treatment with Promogran was modelled for a maximum of three months. Country-specific treatment costs were used to estimate the incremental cost per ulcer-free day gained over 12 months. Some parameter assumptions were changed to assess the sensitivity of the results. RESULTS: Within the first three months of treatment, 26% of ulcers in the Promogran cohort healed compared with 20.7% in the GWC cohort. Over the 12 months, the average number of months spent in the healed state was 3.41 (GWC) and 3.75 (Promogran). Promogran treatment was found to be cost-saving in all four countries, using year 2000 Euro values. CONCLUSION: Promogran with GWC may be cost-effective, perhaps even cost-saving, under a wide variety of assumptions for the treatment of neuropathic foot ulcers. DECLARATION OF INTEREST: This study was funded by Ethicon Gmbh (Johnson and Johnson), Germany.

Bandages↗
PubMed2001

Cost effectiveness of Becaplermin in the treatment of diabetic foot ulcers in four European countries.

OBJECTIVE: The primary objective of this study was to estimate the cost effectiveness of treating diabetic foot ulcers with becaplermin (Regranex) plus good wound care (GWC) compared with GWC alone in a variety of European healthcare settings. A secondary objective was to analyse the effect of different treatment practices on the economics of caring for diabetic foot ulcers. DESIGN AND SETTING: Markov-based simulation study from the perspective of a national health system. METHODS: A 12-month Markov computer simulation model was used to assess the cost effectiveness in 4 European countries of treating diabetic foot ulcers with becaplermin plus GWC versus GWC alone. Transition probabilities were taken from a prospective study of 183 patients and becaplermin efficacy was based on 20-week healing rates in a recent meta-analysis of clinical trials involving 449 patients. Country-specific treatment cost data were collected in collaboration with local economic consultations and combined with the disease model to estimate the incremental cost per ulcer-free month gained. The model was then run using hypothetical low- and high-intensity resource usage profiles to investigate the economics of caring for diabetic foot ulcers. RESULTS: Over the course of 1 year, individuals who received becaplermin plus GWC were, on average, predicted to spend an additional 0.81 months (24% longer) free of ulcers and to experience a 9% lower risk of undergoing a lower extremity amputation than individuals who received GWC alone. Consequently, becaplermin plus GWC was estimated to be net cost saving in Sweden, Switzerland and the UK. In France, the addition of becaplermin was estimated to add $US19 (1999 values) for each additional ulcer-free month gained. There were substantial intercountry differences in treatment practices and the costs of treating diabetic foot ulcers. CONCLUSIONS: Becaplermin may be a cost-effective treatment for neuropathic diabetic foot ulcers in a wide range of European settings. In Sweden, Switzerland and the UK, becaplermin may even be cost saving. Substantial intercountry differences in resource patterns appear, at least partly, to be the logical outcome of differences in unit costs.

Becaplermin↗
PubMed2000

Molecular detection of an Ehrlichia-like agent in rainbow trout (Oncorhynchus mykiss) from Northern California.

Ehrlichia DNA was identified by nested PCR in rainbow trout (Oncorhynchus mykiss) collected from a creek in northern California where Potomac horse fever is endemic. Ehrlichia DNA was found in tissues from several organs including the gills, heart, spleen, liver, kidneys and intestine of trout and from three different adult digenetic trematodes (Deropegus sp., Crepidostomum sp., Creptotrema sp.) parasitizing the gallbladder and/or the intestine of the trout. Sequencing of PCR-amplified DNA from the 16S rRNA gene indicated that the source organism was most closely related to the sequences of E. risticii (level of sequence similarity 96.0%), the SF agent (95.9%), E. sennetsu (95.8%), and Neorickettsia helminthoeca (95.3%). The data suggest that trout and parasitic trematodes may be involved in the epidemiology of an Ehrlichia-like agent belonging to the E. sennetsu genogroup. Whether the fish agent infects horses, dogs, or human beings, and whether it causes disease, remain to be determined.

Animals↗
PubMed2000

Development of an instrument for monitoring adolescent health issues.

The aim of the project was to develop a survey instrument to monitor relevant health status and health-related behaviors among secondary school students. The development of the instrument occurred in three main phases: collection of existing surveys, workshops with relevant health professionals and focus groups with adolescents. The topics for inclusion were refined using Health Goals and Targets for Australian Children and Youth and consultations with health professionals, and included alcohol/illicit drug use, smoking, nutrition, exercise, injury, mental health, violence and sexual health. Content validity was demonstrated through a comprehensive literature review, review and application of existing instrumentation, dialog and exchange with health professionals, and focus groups with adolescents. The process of peer review through correspondence with health professionals, and the coordination of workshops and focus groups established face validity. Responses from students also indicated that they interpreted the questions as intended. The instrument was piloted in five secondary schools during class periods. Process evaluation was also conducted to determine the appropriateness of the survey and the procedures used in administering the survey. Feedback from school staff was supportive and favorable with respect to the choice of issues. Reliability was assessed by a test-re-test procedure 2 weeks apart. In general, most of the questions showed moderate to high reliability (kappa > 0.5) indicating agreement of 50% or greater. This instrument was developed as a monitoring instrument and places emphasis on determining prevalence levels of a range of health issues and health behaviors to assist with identifying clustering patterns of negative health outcomes. Although the instrument is primarily for use with students in school hours, the nature of the instrument allows modification for use in older groups of adolescents and out-of-school youth. The final version of the questionnaires for senior and junior students can be accessed via the Internet (http://;+www.spmed.uq.edu.au/CHPCPR /qu estionnaire).

Adolescent↗
PubMed2000

International comparison of health care systems using resource profiles.

The most frequently used bases for comparing international health care resources are health care expenditures, measured either as a fraction of gross domestic product (GDP) or per capita. There are several possible reasons for this, including the widespread availability of historic expenditure figures; the attractiveness of collapsing resource data into a common unit of measurement; and the present focus among OECD member countries and other governments on containing health care costs. Despite important criticisms of this method, relatively few alternatives have been used in practice. A simple framework for comparing data underlying health care systems is presented in this article. It distinguishes measures of real resources, for example human resources, medicines and medical equipment, from measures of financial resources such as expenditures. Measures of real resources are further subdivided according to whether their factor prices are determined primarily in national or global markets. The approach is illustrated using a simple analysis of health care resource profiles for Denmark, France, Germany, Sweden, the United Kingdom, and the USA. Comparisons based on measures of both real resources and expenditures can be more useful than conventional comparisons of expenditures alone and can lead to important insights for the future management of health care systems.

Delivery of Health Care↗
PubMed1998

Ligand-targeted liposomes.

Liposomes have gained increased attention as systemic drug delivery vehicles following recent regulatory approvals of several vesicle-formulated drugs. These products have demonstrated improved therapeutic indices over their corresponding conventional drugs by avoiding sensitive tissues and/or increasing delivery to specific targets in vivo. They have achieved these improvements primarily through physical means: (1) by retaining drug within vesicles while in the circulation, thus avoiding or minimizing uptake by sensitive normal tissues; and (2) by selectively extravasating into target tissues, releasing active drug. In order to improve upon these therapies in the future, clinically active liposome delivery systems most likely will need to include site-directed surface ligands to further enhance their selective delivery. This may be crucial for the in vivo transport and delivery of macromolecules, including antisense, oligonucleotide aptamers, and genes, which-unlike most conventional drugs-do not circulate well and often require cellular uptake by fusion, endocytosis, or other processes to reach their active sites. This manuscript reviews technologies applicable to directing liposomes and their contents to selected in vivo targets using surface-bound, site-specific ligands. Presented are the biological barriers to be overcome, criteria for selecting the determinants to be targeted, various targeting ligands and overall delivery system design considerations. Several novel targets as well as novel ligand constructs for site-directed therapy are reviewed and discussed. Systemic liposome therapy, which currently must be administered by the intravenous route, is the principal focus of this analysis.

Journal Article↗
PubMed1997

Inorganic species in geologic fluids: correlations among standard molal thermodynamic properties of aqueous ions and hydroxide complexes.

Correlations among experimentally determined standard partial molal thermodynamic properties of inorganic aqueous species at 25 degrees C and 1 bar allow estimates of these properties for numerous monatomic cations and anions, polyatomic anions, oxyanions, acid oxyanions, neutral oxy-acid species, dissolved gases, and hydroxide complexes of metal cations. Combined with correlations among parameters in the revised Helgeson-Kirkham-Flowers (HKF) equation of state (Shock et al., 1992), these estimates permit predictions of standard partial molal volumes, heat capacities, and entropies, as well as apparent standard partial molal enthalpies and Gibbs free energies of formation to 1000 degrees C and 5 kb for hundreds of inorganic aqueous species of interest in geochemistry. Data and parameters for more than 300 inorganic aqueous species are presented. Close agreement between calculated and experimentally determined equilibrium constants for acid dissociation reactions and cation hydrolysis reactions supports the generality and validity of these predictive methods. These data facilitate the calculation of the speciation of major, minor, and trace elements in hydrothermal and metamorphic fluids throughout most of the crust of the Earth.

Algorithms↗
PubMed1997

Use of nested polymerase chain reaction to identify feline herpesvirus in ocular tissue from clinically normal cats and cats with corneal sequestra or conjunctivitis.

OBJECTIVE: To use a nested polymerase chain reaction (PCR) to detect feline herpesvirus (FHV-1) DNA in conjunctiva or cornea from clinically normal cats and cats with conjunctivitis or corneal sequestra. SAMPLES: Conjunctival snip biopsy specimens from 50 cats with conjunctivitis and 50 clinically normal cats; 28 keratectomy specimens from 26 cats with sequestra, and 13 specimens from clinically normal cats. PROCEDURE: Tissue specimens were digested, and FHV-1 DNA was amplified, using a double round of PCR. Products were visualized by use of agarose gel electrophoresis. RESULTS: Polymerase chain reaction was positive in 27 of 50 (54%) conjunctival specimens from cats with conjunctivitis and 6 of 50 (12%) specimens from clinically normal cats. Difference in the results between cats with conjunctivitis and clinically normal cats was statistically significant. Polymerase chain reaction was positive in 5 of 28 (18%) corneal specimens from cats with sequestra and 6 of 13 (46%) clinically normal cats. Distribution of positive results between clinically normal cats and those with sequestra was not significant. CONCLUSION: Cats with conjunctivitis were more likely to have a positive PCR result than were clinically normal cats, making it likely that FHV-1 was associated with the disease state. Herpesvirus DNA could not be detected in most corneas from cats with sequestra. CLINICAL RELEVANCE: Polymerase chain reaction is a useful clinical test for identifying FHV-1 DNA in cats with conjunctivitis, yielding greater sensitivity over that of current available tests. Herpesvirus may be less of a cause of corneal sequestration in the commonly affected breeds, Himalayan and Persian, than other factors, such as lagophthalmos or corneal metabolic defects.

Acute Disease↗
PubMed1997

Comparison of nested polymerase chain reaction, virus isolation, and fluorescent antibody testing for identifying feline herpesvirus in cats with conjunctivitis.

OBJECTIVE: To compare nested polymerase chain reaction (PCR), virus isolation (VI), and fluorescent antibody (FA) testing to detect feline herpesvirus (FHV) in cats with naturally acquired conjunctivitis or respiratory tract disease, or both. SAMPLES: Swab and microbrush specimens from the conjunctiva and throat were taken from 46 cats, allotted to 3 groups (conjunctivitis only, respiratory tract disease and conjunctivitis, and clinically normal). PROCEDURE: Cells from microbrush specimens were digested and herpesvirus DNA was amplified, using a double round of PCR. Products were detected by use of agarose gel electrophoresis. The VI and FA tests were performed in routine manner. RESULTS: Of 16 cats with conjunctivitis only, conjunctival specimens from 8 and throat specimens from 8 were FHV positive by PCR. None had positive results of VI or FA testing. Of 15 cats with respiratory tract disease and conjunctivitis, conjunctival specimens from 13 and throat specimens from 12 were FHV positive by PCR. A conjunctival specimen from 1 cat and throat specimens from 3 cats were FHV positive by VI. A conjunctival specimen from 1 cat was FHV positive by FA testing. Of 15 clinically normal cats, conjunctival and throat specimens from 2 cats were FHV positive by PCR; neither conjunctival nor throat specimens from these cats were FHV positive by VI or FA testing. CONCLUSION: For cats with respiratory tract disease and conjunctivitis, or with conjunctivitis only, nested PCR was more sensitive at detecting FHV than was VI or FA testing. CLINICAL RELEVANCE: Nested PCR is a more sensitive test than the currently available VI and FA tests for identifying FHV in cats with conjunctivitis.

Animals↗
PubMed1994

Barium ions fail to support neurotransmission at a central synapse.

Synaptic transmission in the CA1 area of the hippocampal slice preparation in vitro was studied in bathing media containing different levels of divalent cations. Transmission was abolished by replacing the normal levels (2.5 mM) of Ca2+ with 3 mM Mg. Transmission was not permanently restored by subsequent addition of Ba2+ but added Ca2+ was effective. Transient reappearance of synaptic currents were seen when Ba2+ was added at a time when contaminating levels of Ca2+ were still present, but neurotransmission waned as [Ca2+]e declined with protracted washout. In accordance with this interpretation, Ba2+ potentiated the transmission observed in the presence of low concentrations (0.25 mM) of Ca2+. Little evidence was found for Ba2+ effects at axonal sites but the potentiation of synaptic transmission by Ba2+ could be accounted for in terms of a blockade of terminal K-channels.

Action Potentials↗
PubMed1994

Benign colonic ulcers associated with nonsteroidal antiinflammatory drug ingestion.

Nonsteroidal antiinflammatory drugs can be associated with benign colonic ulcers. The ulcers are easily diagnosed by colonoscopy, and, if uncomplicated, they are best treated by cessation of the nonsteroidal antiinflammatory drugs. Benign colonic ulcers should be included in the differential diagnosis of any patient who presents with gastrointestinal complaints and is taking nonsteroidal antiinflammatory drugs.

Aged↗