Biomedical subjects
P Martin
Publications and source records attributed to P Martin.
Surveillance of listeria infections in Europe.
In addition to the economic consequences and threats associated with outbreaks, listeriosis remains of great public health concern, as it has one of the highest case fatality rates of all the foodborne infections (20%-30%), and has common source epidemic potential. Changes in the way food is produced, distributed and stored have created the potential for diffuse and widespread outbreaks involving many countries. In 2002, a survey was carried out to assess the need for and the feasibility of a European network on listeria infections in humans. Data on surveillance systems and laboratory methods were collected through two postal surveys sent to the national Centres for communicable disease surveillance and to the listeria reference laboratories. Surveillance systems for listeria infections were in operation in 16 out of the 17 countries surveyed, and 16 countries had a national reference laboratory (NRL). All countries based their case definition of listeriosis on the isolation of Listeria monocytogenes. Fourteen NRLs performed at least one typing method on human strains. At least 13 countries already carried out or expressed willingness to carry out characterisation of isolates by pulsed field gel electrophoresis (PFGE) of L. monocytogenes strains isolated from human cases following a standard protocol. The participants concluded that there was a clear added value to having a European surveillance network for listeria infections, particularly for outbreak detection and investigation, and that a surveillance network based on the existing national surveillance systems was feasible.
A collection of bovine cDNA probes for gene expression profiling in muscle.
Array technology has been increasingly used to monitor global gene expression patterns in various tissues and cell types. However, applications to muscle development and pathology as well as meat production in livestock species have been hampered by the lack of appropriate cDNA collections. To overcome this problem, a directed cDNA library was constructed starting from 23 muscles of meat-producing bovines to derive a collection of 3573 clones. A preliminary sequence characterization of this collection indicated that the most abundant transcripts correspond to genes encoding proteins involved in energy metabolism (COX and NADH dehydrogenase subunits) and belonging to the contractile apparatus (myosin chains and troponin isoforms). From this cDNA library, we selected a set of 435 clones representing 340 unique genes, of which 24 were novel. This collection was subsequently completed with 75 specific cDNA probes for genes of interest already studied in our laboratory. The bovine 'muscle' cDNA repertoire thus designed was spotted onto a nylon membrane (macroarray) in order to test its utility to further investigate the transcriptome of bovine muscles in relation to meat quality traits. It is also anticipated that this type of collection might be useful for the study of chronic myologic diseases in other mammalian species, including humans.
Measurements of the MHD dynamo in the quasi-single-helicity reversed-field pinch.
The first experimental study of the MHD dynamo in a quasi-single-helicity (QSH) reversed-field pinch toroidal plasma is presented. In QSH plasmas, a dominant wave number appears in the velocity fluctuation spectrum. This velocity component extends throughout the plasma volume and couples with magnetic fluctuations to produce a significant MHD dynamo electric field. The narrowing of the velocity fluctuation spectrum and the single-mode character of the dynamo are features predicted by theory and computation, but only now are observed in experiment.
Feedback stabilization of multiple resistive wall modes.
Active feedback stabilization of multiple independent resistive wall modes is experimentally demonstrated in a reversed-field pinch plasma. A reproducible simultaneous suppression of several nonresonant resistive wall modes is achieved. Coupling of different modes due to the limited number of the feedback coils is observed in agreement with theory. The feedback stabilization of nonresonant RWMs also has an effect on tearing modes that are resonant in the central plasma, leading to a significant prolongation of the discharge pulse.
Meta-analysis: the effect of age on immunological response to hepatitis B vaccine in end-stage renal disease.
BACKGROUND: Patients on maintenance dialysis typically show a suboptimal immune response to hepatitis B virus vaccine compared with the non-uraemic population. A variety of inherited or acquired factors have been implicated in this diminished response. Age-associated changes in immune status may contribute to decreased vaccine efficacy in older individuals although contradictory results have been reported in individuals with normal kidney function. AIMS: To evaluate the relationship between age and immune response to hepatitis B vaccine in patients with end-stage renal disease by performing a systematic review of the literature with a meta-analysis of clinical trials. METHOD: We used the random effects model of DerSimonian and Laird; sources of heterogeneity in effect estimates were explored by performing sensitivity analyses. RESULTS: We identified 17 clinical trials (1800 unique patients); six (35%) were controlled studies. Pooling of study results demonstrated a significantly decreased risk of response to hepatitis B vaccine among older dialysis patients (overall risk ratio: 0.74; 95% confidence intervals: 0.70-0.79). The P-value was 0.0139 for our test of study heterogeneity. A lowered risk of response to hepatitis B vaccine persisted after exclusion of trials based on plasma-derived vaccines; it was present even when 'older' individuals were defined as being as 50 years (RR: 0.85, 95% CI: 0.75-0.96) or more (cut-off 60 years RR: 0.75; 95% CI: 0.66-0.85). An effect of age on seroprotection rate was present in all clinical reports, irrespective of the geographic origin of the study group: Europe (RR: 0.76; 95% CI: 0.70-0.83) North America (RR: 0.67; 95% CI: 0.60-0.74) or other countries (RR: 0.83; 95% CI: 0.71-0.97). Additional doses of vaccine did not appear to have an impact on RR of response by age. CONCLUSIONS: Our meta-analysis showed a clear association between older age and impaired response to hepatitis B virus vaccine in end-stage renal disease patients. Such a relationship is biologically plausible. Vaccination schedules with adapted vaccine doses and frequent serum testing for loss of immunity against hepatitis B virus are recommended in elderly patients on maintenance dialysis.
Particle-transport analysis in reversed field pinch helical states.
This Letter reports the result of a numerical study of particle transport in self-organized single helicity (SH) and quasi-SH reversed field pinch plasmas. Our code, benchmarked against experimental data, predicts a large improvement in particle transport for SH compared to the standard multiple helicity states. The contribution of neoclassical effects is noted. An estimate of the ambipolar electric field in helical states and in fully stochastic magnetic fields is given.
Sirolimus-induced hyperlipidaemia in liver transplant recipients is not dose-dependent.
BACKGROUND: Sirolimus is a potent immunosuppressive medication that acts by inhibiting T-cell proliferation. It has been used in kidney transplantation because of its lack of nephrotoxicity. It is now being investigated in liver transplantation, but there are concerns about safety and long-term side effects such as dyslipidaemia. Hypertriglyceridaemia is a common adverse event seen with sirolimus use, and often does not respond to dose reduction or anti-lipemic drugs. METHOD: We report six patients who have developed significant hyperlipidaemia while receiving sirolimus, in spite of therapeutic trough levels. CONCLUSION: All six patients showed either resolution or improvement in lipid levels with discontinuation of sirolimus.
Observations of multiple magnetic islands in the core of a reversed field pinch.
We describe in this Letter the first measurement of multiple islands in the core of a reversed field pinch (RFP). These islands appear with current profile modification leading to magnetic fluctuation reduction in the Madison symmetric torus RFP. Magnetic island widths decrease to an unprecedented level, reducing the overlap of adjacent islands and allowing distinct islands to appear. The structures are observed in multichord measurements of soft-x-ray emissivity. The soft-x-ray data is validated with Poincaré reconstructions of the magnetic field structure in the core.
Genetic immunization and comprehensive screening approaches in HLA-A2 transgenic mice lead to the identification of three novel epitopes in hepatitis C virus NS3 antigen.
Interferon-gamma (IFN gamma)-producing CD8+ T cells have been shown to play a key role in the control or eradication of hepatitis C virus (HCV) infections. In particular, T cells specific of the non-structural protein 3 (NS3) are often associated with control of viremia. The aim of the study was to identify novel HLA-A2 restricted CD8+ T cell epitopes specific of NS3 using a combination of comprehensive approaches. HLA-A2.1 transgenic mice were immunized with a DNA vaccine optimized for NS3 specific epitope presentation and induced CD8+ T cell reactivity was screened using 42 algorithm-predicted peptides as well as a library of 78 overlapping 15-mer peptides spanning the whole protein. Three epitopes mapping within the NS3 protease (GLL: aa 1038-1047) or helicase (ATL: aa 1260-1268 and TLH: aa 1617-1625) were identified. These epitopes, which display similar and high in vitro binding capacities to soluble HLA-A2 molecules, are able to induce either cytotoxic T lymphocytes (CTL) and/or IFN gamma-producing T cells. Comparative in vitro target cell sensitization studies revealed a higher immunogenicity of the GLL peptide as compared with both ATL and TLH peptides. This peptide was capable to recall in vitro HCV-specific IFN gamma and IL-10-producing T cells from peripheral blood mononuclear cells (PBMC) of chronically infected patients. These data increase the pool of NS3-specific CD8+ T cell epitopes available to analyze HCV associated immunity and could contribute to the design and evaluation of candidate vaccines.
Cerebral vasculitis caused by Aspergillus species in an immunocompetent adult.
We describe a case of cerebral vasculitis due to Aspergillus infection in an immunocompetent adult, in whom the probable source was paranasal sinus infection. At postmortem there was widespread endovascular Aspergillus infection of the cerebral arteries with occlusion of the basilar artery. We review the literature regarding intracranial Aspergillus infection and new approaches to diagnosis.
A radon and meteorological measurement network for the Alligator Rivers Region, Australia.
The network described in this paper has been set up to provide detailed time-series data on concentrations of 222Rn in air at various locations within the Alligator Rivers Region, over a time frame of several years. These data will be important in assessing the effects of uranium mining operations on radon levels in the region, both in providing baseline and monitoring data and in calibrating and verifying predictive models. At present, three stations are operating in the region with a fourth being commissioned. Each station logs half hourly average radon concentrations and relevant meteorological data (wind speed, direction and variability, air pressure and temperature, relative humidity, soil temperature, rain and sunshine rates). It is intended to operate the four stations at selected locations for one- or two-year intervals, at the end of which three will be moved to new locations (one station at Mudginberri will be kept as a constant control station). Sites for which extensive datasets are currently available include: Jabiru Town, Jabiru East, Djarr Djarr, East Alligator Ranger Station and Nabarlek minesite. Illustrative data from these sites are presented.
Concurrent Fusarium chlamydosporum and Microsphaeropsis arundinis infections in a cat.
A 7-year-old cat was presented initially with multiple draining sinuses on the metatarsal region of its right hindlimb. Another lesion had appeared at the same time on the fifth proximal interphalangeal joint of the left forelimb. Histopathological examination of a biopsy from the right hindlimb lesion revealed chronic pyogranulomatous inflammation associated with yeast-like bodies and septate mycelia; a fungus was cultured on conventional media but not identified further. Culture of a swab collected from the left forelimb lesion demonstrated a pigmented fungus, also not characterised further. Although there was initially a favourable response to ketoconazole (Nizoral, Janssen-Cilag Pty. Ltd) and beta-lactam therapy, the infection in the hind limb relapsed subsequently, and Fusarium chlamydosporum was cultured from deep biopsy specimens. Clinical improvement followed debridement and itraconazole (Sporanox, Janssen-Cilag Pty. Ltd; 100 mg orally once daily), however amputation of the limb represented the best chance for a cure. The cat made an uncomplicated recovery following surgery and remained well for five months until the lesion on the left forelimb recurred. Amputation of the distal fourth digit was then performed, and the resected tissue submitted for culture. The dematiaceous fungus Microsphaeropsis arundinis was subsequently cultured. The cat remained well for several months, until a further F. chlamydosporum infection developed on the body wall. This was excised 7 months ago, and no lesions have recurred in this area. Importantly, this is the first reported case of M. arundinis infection in a mammalian host.
Lower respiratory tract infections in cats: 21 cases (1995-2000).
Twenty-one lower respiratory tract infections diagnosed in cats at University of Sydney Veterinary Centre between 1995 and 2000 were identified retrospectively. Patient records were analysed to determine historical, clinical, clinicopathologic and radiographic features of lower respiratory tract infections. Response to therapy was also assessed. Infectious agents identified were Mycoplasma spp., Pasteurella spp., Bordetella bronchiseptica, Salmonella typhimurium, Pseudomonas sp., Mycobacterium thermoresistible, Cryptococcus neoformans, Toxoplasma gondii, Aelurostrongylus abstrusus and Eucoleus aerophilus. The study provides a detailed retrospective analysis of infectious lower respiratory tract disease in this population of cats.
A retrospective analysis of feline bronchoalveolar lavage cytology and microbiology (1995-2000).
A retrospective study of 88 bronchoalveolar lavage specimens from 80 cats presenting to the University of Sydney Veterinary Centre between 1995 and 2000 was performed. Bronchoalveolar lavage cytology and microbiology in conjunction with other diagnostic aids and patient records were used to classify cases as lower respiratory tract infections (LTRIs), LRTI revisits, feline bronchial disease, cardiac disease, neoplastic disease and multisystemic disease. Cases for which a definitive diagnosis could not be made were classified as inconclusive. Infectious agents identified were Mycoplasma spp., Pasteurella spp., Bordetella bronchiseptica, Salmonella typhimurium, Pseudomonas sp., Cryptococcus neoformans, Aelurostrongylus abstrusus and Eucoleus aerophilus. The study highlights the importance of bronchoalveolar lavage cytology and microbiology in the evaluation of feline lower respiratory tract disease.
Twenty-five cases of feline bronchial disease (1995-2000).
Twenty-five cases of feline bronchial disease were identified retrospectively. The criteria for inclusion were consistent clinical signs or histopathology and no other identifiable aetiology. Patient records were analysed to determine historical, clinical, clinicopathologic and radiographic features. The main presenting complaints were coughing and dyspnoea. The most common physical finding was dyspnoea. The majority of radiographs had a bronchial pattern either as the sole change or as a component of a mixed pattern. Bronchoalveolar lavage cytology was neutrophilic or eosinophilic in the majority of cats. There was no association between age, breed, sex, clinical signs, bronchoalveolar lavage cytology or radiographic severity and disease severity.
[Busulfan and cycosporin in bone graft children].
Most drugs exhibit both inter- and intra-individual pharmacokinetic and pharmacodynamic variability. This variability explains the different responses observed in patients exposed to standard doses and must be taken into consideration when the therapeutic window is narrow. Population pharmacokinetics provides mean (or median) values of pharmacokinetic parameters as well as the distribution pattern and the statistical relationship with covariables in a group of individuals presenting common characteristics. Among the different methods developed for population pharmacokinetics, the data pool method, as well as the two-step and one-step methods (NONMEM and NPEM) are attractive. Population models can then be developed using bayesian logistics to obtain an estimation of the pharmacokinetic parameters of a given patient and predict the most adapted dose in light of the therapeutic target (residual serum concentration, mean concentration.). Busulfan is an alkylizing agent used instead of radiotherapy for pre-graft preparation before bone marrow grafts in children. This compound requires dose monitoring because of its narrow therapeutic window: under-dosing raises the risk of graft rejection; inversely over-dosing can cause potentially fatal complications such as occlusive venous disease. Interindividual variability is characteristic of busulfan kinetics. Several factors can explain part of this variability: age, underlying disease, changes in liver function, drug bioavailability, chronobiology. The short treatments used (most protocols have 16 doses given in four days) require rapid monitoring to propose effective adjustments. In this context, use of bayesian logistics to estimate the patient's pharmokinetic parameters is very useful for correct dosing. This type of monitoring could also be used for other compounds such as cyclosporine, with a narrow therapeutic window.