Search PubMed⌕ Search

Biomedical subjects

Paul Martin

Publications and source records attributed to Paul Martin.

At least 19 recordsLinked to original sources
PubMed2006

Management of HCV infection and liver transplantation.

A major challenge facing liver transplant recipients and their physicians is recurrence of hepatitis C virus infection following otherwise technically successful liver transplantation. Recurrent infection leads to diminished graft and patient survival. Although a number or predictors of severe recurrence have been identified, no definitive strategy has been developed to prevent recurrence. Generally the tempo of hepatitis C recurrence is gauged by serial liver biopsies with the decision to intervene with antiviral therapy based on local philosophy and expertise. Treating hepatitis C in this population has a number of major challenges including diminished patient tolerance for side-effects as well as managing the patient's immunesuppression. However sustained viral responses are possible with the potential to reduce the impact of recurrent hepatitis on the graft. However recurrent hepatitis C virus infection will remain the most frequent form of recurrent disease in liver transplant programs for the foreseeable future.

Journal Article↗
PubMed2006

Geographic variability in radon exhalation at a rehabilitated uranium mine in the Northern Territory, Australia.

In this study, dry season radon flux densities and radon fluxes have been determined at the rehabilitated Nabarlek uranium mine in northern Australia using conventional charcoal canisters. Environmental background levels amounted to 31+/- 15 milli Becquerel per m(2) per second (mBq m(-2) s(-1)). Radon flux densities within the fenced rehabilitated mine area showed large variations with a maximum of 6500 mBq m(-2) s(-1) at an area south of the former pit characterised by a disequilibrium between (226)Ra and (238)U. Radon flux densities were also high above the areas of the former pit (mean 971 mBq m(-2) s(-1)) and waste rock dump (mean 335 mBq m(-2) s(-1)). The lower limit for the total pre-mining radon flux from the fenced area (140 ha) was estimated to 214 kBq s(-1), post-mining radon flux amounted to 174 kBq s(-1). Our study highlights that the results of radon flux studies are vitally dependant on the selection of individual survey points. We suggest the use of a randomised system for both the selection of survey points and the placement of charcoal canisters at each survey point, to avoid over estimation of radon flux densities. It is also important to emphasize the significance of having reliable pre-mining radiological data available to assess the success of rehabilitation of a uranium mine site.

Air Pollutants, Radioactive↗
PubMed2006

Hepatic encephalopathy: a neurochemical, neuroanatomical, and neuropsychological study.

Hepatic encephalopathy (HE) is normally diagnosed by neuropsychological (NP) tests, which are not very specific and do not reveal the underlying pathology. Magnetic resonance imaging (MRI) and spectroscopy (MRS) of the brain offer alternative and possibly more specific markers for HE. These methods were applied in conjunction with NP testing in order to determine their usefulness in the identification of HE and to understand the pathogenesis of HE more clearly. MR imaging and spectroscopy examinations, in addition to a battery of 15 NP tests, were administered to investigate 31 patients awaiting liver transplantation and 23 healthy controls. MR image intensities from the globus pallidus region were calculated and normalized to those of the thalamus. Absolute concentrations and ratios with respect to creatine (Cr) of several metabolites were computed from MR spectra. The MR data were correlated with the results of NP tests. The patients showed impairment in NP tests of attention and visuospatial and verbal fluency. In T1-weighted MRI, the relative intensity of the globus pallidus with respect to that of the thalamus region was significantly elevated in patients and correlated(negatively) with three NP tests (Hooper, FAS, and Trails B). The absolute concentrations of myo-inositol (mI) and choline (Ch) were significantly reduced in three brain regions. In addition, the absolute concentrations of glutamine (Gln) and combined glutamate and glutamine (Glx) were increased in all three locations, with Gln increase being significant in all areas while that of Glx only in the occipital white matter. In summary, this study partially confirms a hypothesized mechanism of HE pathogenesis, an increased synthesis of glutamine by brain glutamate in astrocytes due to excessive blood ammonia, followed by a compensatory loss of myo-inositol to maintain astrocyte volume homeostasis. It also indicates that the hyperintensity observed in globus pallidus could be used as complementary to the NP test scores in evaluating the mental health of HE patients.

Adult↗
PubMed2006

The lead isotopic composition of dust in the vicinity of a uranium mine in northern Australia and its use for radiation dose assessment.

Airborne lead isotope ratios were measured via Thermal Ionisation Mass Spectrometry in samples from the vicinity of Ranger uranium mine in northern Australia. Dust deposited on leaves of Acacia spp. was washed off and analysed to gain a geographical snapshot of lead isotope ratios in the region. Aerosols were also collected on Teflon filters that were changed monthly over one seasonal cycle using a low volume diaphragm pump. Lead isotope ratios in dust deposited on leaves overestimate the relative amount of mine origin airborne lead, most likely due to a difference of the size distribution of particles collected on leaves and true aerosol size distribution. Seasonal measurements show that the annual average mine contribution to airborne lead concentrations in Jabiru East, approximately 2.5 km northwest of the mine, amounted to 13%, with distinct differences between the wet and dry season. The relative contribution of mine origin lead deposited on leaves in the dry season drops to less than 1% at a distance of 12.5 km from the mine along the major wind direction. An approach is outlined, in which lead isotope ratios are used to estimate the effective radiation dose received from the inhalation of mine origin radioactivity trapped in or on dust. Using the data from our study, this dose has been calculated to be approximately 2 microSv year(-1) for people living and working in the area.

Acacia↗
PubMed2006

Toward biomarkers for chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: III. Biomarker Working Group Report.

Biology-based markers that can be used to confirm the diagnosis of chronic graft-versus-host disease (GVHD) or monitor progression of the disease could help in the evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biologic or pathogenic process, a pharmacologic response to a therapeutic intervention, or a surrogate end point intended to substitute for a clinical end point. The following applications of biomarkers could be useful in chronic GVHD clinical trials or management: (1) predicting response to therapy; (2) measuring disease activity and distinguishing irreversible damage from continued disease activity; (3) predicting the risk of developing chronic GVHD; (4) diagnosing chronic GVHD: (5) predicting the prognosis of chronic GVHD; (6) evaluating the balance between GVHD and graft-versus-leukemia effects (graft-versus-leukemia or GVT); and (7) serving as a surrogate end point for therapeutic response. Such biomarkers can be identified by either hypothesis-driven testing or by high-throughput discovery-based methods. To date, no validated biomarkers have been established for chronic GVHD, although several candidate biomarkers have been identified from limited hypothesis-driven studies. Both approaches have merit and should be pursued. The consistent treatment and standardized documentation needed to support biomarker studies are most likely to be satisfied in prospective clinical trials.

Biomarkers↗
PubMed2006

Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group report.

The lack of standardized criteria for quantitative measurement of therapeutic response in clinical trials poses a major obstacle for the development of new agents in chronic graft-versus-host disease (GVHD). This consensus document was developed to address several objectives for response criteria to be used in chronic GVHD-related clinical trials. The proposed measures should be practical for use both by transplantation and nontransplantation medical providers, adaptable for use in adults and in children, and focused on the most important chronic GVHD manifestations. The measures should also give preference to quantitative, rather than semiquantitative, measures; capture information regarding signs, symptoms, and function separately from each other; and use validated scales whenever possible to demonstrate improved patient outcomes and meet requirements for regulatory approval of novel agents. Based on these criteria, we propose a set of measures to be considered for use in clinical trials, and forms for data collection are provided (). Measures should be made at 3-month intervals and whenever major changes are made in treatment. Provisional definitions of complete response, partial response, and progression are proposed for each organ and for overall outcomes. The proposed response criteria are based on current expert consensus opinion and are intended to improve consistency in the conduct and reporting of chronic GVHD trials, but their use remains to be demonstrated in practice.

Adolescent↗
PubMed2006

Provider-patient in-office discussions of response to hepatitis C antiviral therapy and impact on patient comprehension.

BACKGROUND & AIMS: Providers need to communicate projected response rates effectively to enable patients with hepatitis C virus to make informed decisions about therapy. This study used interactional sociolinguistics (1) to evaluate how gastroenterologists and allied health professionals communicate information regarding response rates to antiviral therapy, (2) to determine how these discussions relate to where the patient is in the continuum of evaluation and treatment, (3) to assess whether patients were aligned with providers in their perceptions of response rates after office visits, and (4) to identify factors that improve provider-patient alignment. METHODS: Gastroenterologists, allied health professionals, and patients with hepatitis C virus were videotaped and audiotaped during regularly scheduled visits. Postvisit interviews were conducted separately with patients and providers. Visits and postvisits were transcribed and analyzed using validated sociolinguistic techniques. RESULTS: The phase of hepatitis C virus treatment shaped the benchmarks of response talk, although across the treatment continuum providers overwhelmingly made strategic use of positive statistics, providing motivation. In postvisit interviews, 55% of providers and patients were aligned on response rates. Patients with a favorable outcome and patients who asked response-related questions in the visit were more likely to be aligned with providers. Areas identified for improvement included the tendency to discuss response rates before an individualized assessment could be made, balancing motivation and accuracy, and assessing the patient's perspective before delivering any bad news, if necessary. CONCLUSIONS: Sociolinguistic analysis provides a powerful tool to evaluate provider-patient interactions and to identify ways to improve in-office communication regarding antiviral therapy.

Adult↗
PubMed2006

Living donor liver transplantation: histological abnormalities found on liver biopsies of apparently healthy potential donors.

OBJECTIVE: With the continued shortage of deceased donor grafts, living donor liver transplantation has become an option for adult liver transplant candidates. In the non-transplant setting, liver biopsy is typically carried out to evaluate clinical or biochemical hepatic dysfunction. In living donor liver transplantation, assessment of histological abnormalities that are undetectable by serological, biochemical and radiological methods might play an important role in donor and recipient outcome. METHODS: Seventy consecutive liver biopsies carried out as part of our evaluation of potential donor candidates for adult-to-adult or adult-to-child living donor liver transplants were analyzed. RESULTS: Of the 70 potential donor candidates who underwent liver biopsy for evaluation for living donor liver transplantation, 67% had an unexpected abnormality, of which steatosis was the most common abnormality (38.5%). A variety of other histopathological abnormalities were found including granulomas of unknown etiology (7%), chronic hepatitis (6%) and a microabscess. None of the histological abnormalities had been suspected despite extensive clinical, serological or radiological investigation. CONCLUSIONS: Among the 70 potential donor candidates for living donor liver transplantation, 34% had unremarkable liver biopsies. The most common abnormality was steatosis (38.5%). These findings suggest that all potential candidates for living donor liver transplants should undergo screening liver biopsies. The precise significance of these changes remains to be determined, including which of these changes are contraindications to liver transplantation. These findings may also have implications in the non-transplant setting as changes ascribed to specific etiologies for liver disease might include changes occurring in apparently healthy individuals.

Adult↗
PubMed2005

Comparative characterization of Listeria monocytogenes isolated from Portuguese farmhouse ewe's cheese and from humans.

In order to investigate the possible relationships between Listeria monocytogenes strains isolated from farmhouse ewe's cheese and clinical strains collected, in partially overlapping dates, from the same geographical area in Portugal, a total of 109 isolates from seven ewe's cheese manufactures (n=94) and from humans (n=15) were characterized by serotyping, RAPD, PFGE and allelic analysis of the virulent actA gene. Serotyping indicated the presence of four different serovars: 1/2a, 1/2b, 1/2c and 4b. The 15 clinical isolates were either serovar 4b (86.7%) or serovar 1/2b (13.3%). Among the 94 isolates from cheese and related environments the serovars prevalence was 1/2a (1.1%), 1/2b (17.0%), 1/2c (12.8%) and, unexpectedly, 4b (69.1%). Based on results obtained with PFGE typing of the strains, 25 genotypes were identified, 10 from farmhouses and 15 from human cases. Isolates from serovars 1/2a and 1/2c were assigned to single genotypes, respectively. Within serovars 1/2b and 4b three and 20 genotypes were established, respectively. RAPD typing of the isolates rendered 18 types indicating the lack of accuracy of the primers used in strain differentiation within serovar 4b. The actA gene typing of the strains showed a prevalence of actA gene type I (90.4%) compared with the rest of the strains that were all actA gene type II (9.6%). In spite of the fact that all the farmhouses were completely independent, the distribution of L. monocytogenes genotypes, intra and inter cheese manufactures, was relatively homogeneous, suggesting the existence of resident strains. In contrast, among human isolates there was a great genetic diversity. There was no common genotype between L. monocytogenes implicated in the cases of listeriosis and these cheese-related isolates, suggesting the absence of a causal relationship.

Animals↗
PubMed2005

Inflammatory cells during wound repair: the good, the bad and the ugly.

Damage to any tissue triggers a cascade of events that leads to rapid repair of the wound - if the tissue is skin, then repair involves re-epithelialization, formation of granulation tissue and contraction of underlying wound connective tissues. This concerted effort by the wounded cell layers is accompanied by, and might also be partially regulated by, a robust inflammatory response, in which first neutrophils and then macrophages and mast cells emigrate from nearby tissues and from the circulation. Clearly, this inflammatory response is crucial for fighting infection and must have been selected for during the course of evolution so that tissue damage did not inevitably lead to death through septicemia. But, aside from this role, exactly what are the functions of the various leukocyte lineages that are recruited with overlapping time courses to the wound site, and might they do more harm than good? Recent knockout and knockdown studies suggest that depletion of one or more of the inflammatory cell lineages can even enhance healing, and we discuss new views on how regulation of the migration of inflammatory cells to sites of tissue damage might guide therapeutic strategies for modulating the inflammatory response.

Animals↗
PubMed2005

Biodiversity: disease threat to European fish.

The deliberate introduction of new species can have unexpected negative consequences and we show here how a recently introduced fish, the invasive Asian cyprinid Pseudorasbora parva, is causing increased mortality and totally inhibiting spawning in an already endangered native fish, the European cyprinid Leucaspius delineatus. This threat is caused by an infectious pathogen, a rosette-like intracellular eukaryotic parasite that is a deadly, non-specific agent. It is probably carried by healthy Asian fish, and could decrease fish biodiversity in Europe, as well as having implications for commercial aquaculture.

Animals↗
PubMed2005

Cell biology: master regulators of sealing and healing.

The protective layer of the epidermis in Drosophila (cuticle) and mice (stratum corneum) are structurally unrelated. Yet new evidence suggests a conserved transcription factor, Grainyhead, controls both their development and the means by which both structures repair themselves.

Animals↗
PubMed2005

The small GTPase Rac plays multiple roles in epithelial sheet fusion--dynamic studies of Drosophila dorsal closure.

The coordinated migration and fusion of epithelial sheets is a crucial morphogenetic tool used on numerous occasions during the normal development of an embryo and re-activated as part of the wound healing response. Drosophila dorsal closure, whereby a hole in the embryonic epithelium is zipped closed late in embryogenesis, serves as an excellent, genetically tractable model for epithelial migration. Using live confocal imaging, we have dissected multiple roles for the small GTPase Rac in this process. We show that constitutive activation of Rac1 leads to excessive assembly of lamellipodia and precocious halting of epithelial sweeping, possibly through premature activation of contact-inhibition machinery. Conversely, blocking Rac activity, either by loss-of-function mutations or expression of dominant negative Rac1, disables the assembly of both actin cable and protrusions by epithelial cells. Movies of mutant embryos show that continued contraction of the amnioserosa is sufficient to draw the epithelial edges towards one another, allowing the zipper machinery to bypass non-functioning regions of leading edge. In addition to illustrating the key role of Rac in organization of leading edge actin, loss-of-function mutants also provide substantive proof that Rac acts upstream in the Jun N-terminal kinase (JNK) cascade to direct epithelial cell shape changes during dorsal closure.

Animals↗
PubMed2005

Enhanced expression of the mannose receptor by endothelial cells of the liver and spleen microvascular beds in the macrophage-deficient PU.1 null mouse.

Mice null for the haematopoietic lineage-specific transcription factor PU.1 lack mature Mphi and are compromised in their ability to clear cellular debris from the blood circulation. We investigated the possibility that non-professional phagocytes may partially compensate for the lack of Mphi in clearance functions. In the absence of Kupffer cells (resident liver Mphi) in the PU.1 null mice, electron microscopy revealed ingested debris in sinusoidal endothelial cells and hepatocytes although debris was also seen free in blood vessels. To investigate whether an increased clearance function of non-professional phagocytes might be linked to expression of Mphi-associated phagocytic and pinocytic receptors by other cells in PU.1 null mouse, we examined expression of several candidate proteins by immunocytochemistry and Western blotting. We found mannose receptor (MR) comparably expressed in PU.1 null and PU.1+ mice liver and spleen whereas class A scavenger receptor was substantially reduced and complement receptor 3 was absent in PU.1 null animals. By morphometric analysis, liver and spleen sinusoidal endothelial cells were seen to express significantly more MR in the PU.1 null mouse. This study provides the first evidence of apparently compensatory alterations in the microvasculature of the Mphi-deficient PU.1 null mouse.

Animals↗
PubMed2005

Treatment alternatives for chronic hepatitis B virus infection: a cost-effectiveness analysis.

BACKGROUND: Treatment options for chronic hepatitis B virus (HBV) infection have disparate risks and benefits. Interferon has clinically significant side effects, and lamivudine is associated with viral resistance. In contrast, adefovir is safe and has lower viral resistance but is more expensive. The most cost-effective approach is uncertain. OBJECTIVE: To determine whether and under what circumstances the improved efficacy of adefovir offsets its increased cost compared with lamivudine or interferon. DESIGN: Cost-utility analysis stratified by hepatitis B e antigen (HBeAg) status. DATA SOURCES: Systematic review of MEDLINE from 1970 to 2005. TARGET POPULATION: Patients with chronic HBV infection, elevated aminotransferase levels, and no cirrhosis. TIME HORIZON: Lifetime. PERSPECTIVE: Third-party payer. INTERVENTIONS: 1) No HBV treatment ("do nothing" strategy), 2) interferon monotherapy, 3) lamivudine monotherapy, 4) adefovir monotherapy, or 5) lamivudine with crossover to adefovir upon resistance ("adefovir salvage" strategy). OUTCOME MEASURE: Incremental cost per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: The "do nothing" strategy was least effective yet least expensive. Compared with the "do nothing" strategy, using interferon cost an incremental 6337 dollars to gain 1 additional QALY. Compared with interferon, the adefovir salvage strategy cost an incremental 8446 dollars per QALY gained. Both the lamivudine and adefovir monotherapy strategies were more expensive yet less effective than the alternative strategies and were therefore dominated. RESULTS OF SENSITIVITY ANALYSIS: In sensitivity analysis, interferon was most cost-effective in health care systems with tight budgetary constraints and a high prevalence of HBeAg-negative patients. LIMITATIONS: These results apply only to patients with chronic HBV infection, elevated aminotransferase levels, and no clinical or histologic evidence of cirrhosis. They do not apply to alternative populations. CONCLUSIONS: Neither lamivudine nor adefovir monotherapy is cost-effective in chronic HBV infection. However, a hybrid salvage strategy reserving adefovir only for lamivudine-associated viral resistance may be highly cost-effective across most health care settings. Interferon therapy may still be preferred in health care systems with limited resources, especially in those serving populations with a high prevalence of HBeAg-negative HBV.

Adenine↗
PubMed2005

Live imaging of wound inflammation in Drosophila embryos reveals key roles for small GTPases during in vivo cell migration.

Aa robust inflammatory response to tissue damage and infection is conserved across almost all animal phyla. Neutrophils and macrophages, or their equivalents, are drawn to the wound site where they engulf cell and matrix debris and release signals that direct components of the repair process. This orchestrated cell migration is clinically important, and yet, to date, leukocyte chemotaxis has largely been studied in vitro. Here, we describe a genetically tractable in vivo wound model of inflammation in the Drosophila melanogaster embryo that is amenable to cinemicroscopy. For the first time, we are able to examine the roles of Rho-family small GTPases during inflammation in vivo and show that Rac-mediated lamellae are essential for hemocyte motility and Rho signaling is necessary for cells to retract from sites of matrix- and cell-cell contacts. Cdc42 is necessary for maintaining cellular polarity and yet, despite in vitro evidence, is dispensable for sensing and crawling toward wound cues.

Animals↗