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Biomedical subjects

E Casey

Publications and source records attributed to E Casey.

At least 19 recordsLinked to original sources

Engineering aspects of a mixed methanotrophic culture in a membrane-aerated biofilm reactor.

Methanotrophic biodegradation using the membrane-aerated biofilm reactor (MABR) is a technology offering several advantages over both conventional biofilm reactors and suspended-cell processes. In this study the oxidation efficiency of a methanotrophic biofilm in a 1.5 litre MABR was investigated. Measurements of oxygen and methane uptake rates together with biofilm thickness were taken for developing biofilms. It was found that the specific rate of metabolic activity of the biofilm was unusually high as determined by the methane and oxygen uptake rates. Microbial activity stratification was evident and the location of stratified layers of oxygen consuming components of the consortium could be manipulated via the intra-membrane oxygen pressure.

Biofilms↗

A comparison of two culture media for the recovery of thermophilic campylobacters in broiler farm samples.

A study to evaluate the performance of two different brands of media (Oxoid, Basingstoke, UK, and Mast Diagnostics, Merseyside, UK) for the isolation of thermophilic campylobacters from a range of broiler farm samples was undertaken. Oxoid media performed significantly better than the Mast formulations with overall Campylobacter recovery rates of 46% and 30.5%, respectively, observed from 213 samples tested (p< or =0.05). Consistently higher recoveries of campylobacters were observed from all samples when the results using both types of media were combined.

Animals↗

Creation of low-copy integrated transgenic lines in Caenorhabditis elegans.

In Caenorhabditis elegans, transgenic lines are typically created by injecting DNA into the hermaphrodite germline to form multicopy extrachromosomal DNA arrays. This technique is a reliable means of expressing transgenes in C. elegans, but its use has limitations. Because extrachromosomal arrays are semistable, only a fraction of the animals in a transgenic extrachromosomal array line are transformed. In addition, because extrachromosomal arrays can contain hundreds of copies of the transforming DNA, transgenes may be overexpressed, misexpressed, or silenced. We have developed an alternative method for C. elegans transformation, using microparticle bombardment, that produces single- and low-copy chromosomal insertions. Using this method, we find that it is possible to create integrated transgenic lines that reproducibly express GFP reporter constructs without the variations in expression level and pattern frequently exhibited by extrachromosomal array lines. In addition, we find that low-copy integrated lines can also be used to express transgenes in the C. elegans germline, where conventional extrachromosomal arrays typically fail to express due to germline silencing.

Animals↗

Biofilm development in a membrane-aerated biofilm reactor: effect of flow velocity on performance.

The effect of liquid flow velocity on biofilm development in a membrane-aerated biofilm reactor was investigated both by mathematical modeling and by experiment, using Vibrio natriegens as a test organism and acetate as carbon substrate. It was shown that velocity influenced mass transfer in the diffusion boundary layer, the biomass detachment rate from the biofilm, and the maximum biofilm thickness attained. Values of the overall mass transfer coefficient of a tracer through the diffusion boundary layer, the biofilm, and the membrane were shown to be identical during different experiments at the maximum biofilm thickness. Comparison of the results with published values of this parameter in membrane attached biofilms showed a similar trend. Therefore, it was postulated that this result might indicate the mechanism that determines the maximum biofilm thickness in membrane attached biofilms. In a series of experiments, where conditions were set so that the active layer of the membrane attached biofilm was located close to the membrane biofilm interface, it was shown that the most critical effect on process performance was the effect of velocity on biofilm structure. Biofilm thickness and effective diffusivity influenced reaction and diffusion in a complex manner such that the yield of biomass on acetate was highly variable. Consideration of endogenous respiration in the mathematical model was validated by direct experimental measurements of yield coefficients. Good agreement between experimental measurements of acetate and oxygen uptake rates and their prediction by the mathematical model was achieved.

Biofilms↗

Oxygen mass transfer characteristics in a membrane-aerated biofilm reactor.

Immobilization of pollutant-degrading microorganisms on oxygen-permeable membranes provides a novel method of increasing the oxidation capacity of wastewater treatment bioreactors. Oxygen mass transfer characteristics during continuous-flow steady-state experiments were investigated for biofilms supported on tubular silicone membranes. An analysis of oxygen mass transport and reaction using an established mathematical model for dual-substrate limitation supported the experimental results reported. In thick biofilms, an active layer of biomass where both carbon substrate and oxygen are available was found to exist. The location of this active layer varies depending on the ratio of the carbon substrate loading rate to the intramembrane oxygen pressure. The thickness of a carbon-substrate-starved layer was found to greatly influence the mass transport of oxygen into the active biomass layer, which was located close to, but not in contact with, the biofilm-liquid interface. The experimental results demonstrated that oxygen uptake rates as high as 20 g m-2 d-1 bar-1 can be achieved, and the model predicts that, for an optimized biofilm thickness, oxygen uptake rates of more than 30 g m-2 d-1 bar-1 should be possible. This would allow membrane-aerated biofilm reactors to operate with much greater thicknesses of active biomass than can conventional biofilm reactors as well as offering the further advantage of close to 100% oxygen conversion efficiencies for the treatment of high-strength wastewaters. In the case of dual- substrate-limited biofilms, the potential to increase the oxygen flux does not necessarily increase the substrate (acetate) removal rate.

Acetic Acid↗

Anti-Beta 2-glycoprotein I antibody isotype and IgG subclass in antiphospholipid syndrome patients.

Beta 2-glycoprotein I (beta2-GPI) is an antigenic target recognised by antiphospholipid antibodies found in association with the antiphospholipid syndrome (APS). In this study, the prevalence of Immunoglobulin M (IgM) and IgA anti-beta2-GPI antibodies was examined in APS patients and compared with IgG antibodies. In addition the value of measuring antibody isotypes and IgG subclass was investigated in the laboratory diagnosis of APS. A solid phase enzyme linked immunosorbent assay was established to measure IgG, IgM and IgA and IgG subclass antibodies to beta2-GPI in patients with APS and a variety of other thrombotic and non-thrombotic disorders. Raised levels of IgM anti-beta2-GPI antibodies were observed in 65% of patients with APS, 21% with systemic lupus erythematosus (SLE), 23% with rheumatoid factor, 4% with stroke, 5% carotid artery stenosis (CAS), 17% with a biological false positive serology for syphilis, 43% with infectious mononucleosis (IM) and 27% with human immunodeficiency virus (HIV). The median value for IgM antibodies to beta2-GPI for all these groups ranged from 2 to 7 arbitrary units (AU). Elevated levels of IgA antibodies to beta2-GPI were found in patients with APS (47%), SLE (13%), rheumatoid factor (26%), CAS (48%), stroke (25%), VDRL false positive serology for syphilis (33%), IM (47%) and HIV (7%). The median value of IgA antibodies to beta2-GPI in all of these groups ranged from 2 to 4 AU. Conversely the median value for IgG anti-beta2-GPI in APS patients was 112 AU compared to 1-4 AU in the other conditions examined. The presence of IgM and IgA antibodies to beta2-GPI was much less specific and sensitive for APS than IgG, with raised levels of these isotypes seen in a variety of thrombotic and non-thrombotic disorders. Elevated levels of IgG1, IgG2, IgG3 and IgG4 antibodies to beta2-GPI were detected in APS patients. While all four IgG anti-beta2-GPI antibody subclasses were represented in APS patients there appeared to be a significant overall skewing towards to the IgG2 subclass.

Antibody Specificity↗

Increased HLA-DR and CD44 antigen expression in the gut: evidence of extraarticular immunological activity in rheumatoid arthritis.

OBJECTIVE: To examine the gastrointestinal (GI) immune system in rheumatoid arthritis (RA) for evidence of activation. METHODS: Duodenal biopsies from 25 patients with RA were obtained by endoscopy. Single cell suspensions from the epithelial layer and lamina propria were prepared. Flow cytometry was used to examine the expression of CD4, CD8, T cell receptor-gammadelta (TCR-gammadelta), TCR-alphabeta, HLA-DR, CD44, and interleukin 2 receptor on gut T lymphocytes. Fifteen disease control (DC) individuals and 6 patients with osteoarthritis (OA) taking longterm nonsteroidal antiinflammatory drug (NSAID) therapy were also investigated. Peripheral blood T lymphocytes from all individuals were examined for the expression of these surface molecules. RESULTS: HLA-DR expression was significantly increased on intraepithelial lymphocytes (IEL) and enterocytes from patients with RA (n = 13) compared with the 2 control groups (p<0.01). Immunohistochemistry also revealed increased expression of HLA-DR on enterocytes from patients with RA. RA IEL (n = 6) expressed significantly higher levels of CD44 (p<0.02). In the lamina propria, a small but significant gammadelta T lymphocyte population (mean 5.5%, range 2-12%) was detected in rheumatoid factor positive RA patients (n = 8) compared with RF negative RA patients (n = 8, mean 2%, range 0.4-6%; p<0.01) and the disease control group (n = 15, mean 2%, range 0.5-5%; p<0.01). None of these changes were detectable in peripheral blood lymphocytes from patients with RA. CONCLUSION: This study demonstrates evidence of activation of specific components of the GI immune system in RA. Peripheral blood T lymphocytes from patients with RA did not show increased expression of activation markers, suggesting that changes in the RA GI tract are not systemic but localized. Moreover, these changes appear to be independent of NSAID therapy.

Adult↗

Using multimedia virtual patients to enhance the clinical curriculum for medical students.

Changes in the environment in which clinical medical education takes place in the United States has profoundly affected the quality of the learning experience. A shift to out-patient based care, minimization of hospitalization time, and shrinking clinical revenues has changed the teaching hospital or "classroom" to a degree that we must develop innovative approaches to medical education. One solution is the Virtual Patient Project. Utilizing state-of-the-art computer-based multimedia technology, we are building a library of simulated patient encounters that will serve to fill some of the educational gaps that the current health care system has created. This project is part of a newly formed and unique organization, the Harvard Medical School-Beth Israel Deaconess Mount Auburn Institute for Education and Research (the Institute), which supports in-house educational design, production, and faculty time to create Virtual Patients. These problem-based clinical cases allow the medical student to evaluate a patient at initial presentation, order diagnostic tests, observe the outcome and obtain context-sensitive feedback through a computer program designed at the Institute. Multimedia technology and authoring programs have reached a level of sophistication to allow content experts (the teaching faculty) to design and create the majority of the program themselves and to allow students to adapt the program to their individual learning needs.

Computer Simulation↗

Invasive pulmonary aspergillosis associated with low dose methotrexate therapy for rheumatoid arthritis: a case report of treatment with itraconazole.

Opportunistic infections complicating low dose methotrexate therapy are rare, consisting predominantly of Pneumocystis carinii pneumonia. We report a case of invasive pulmonary aspergillosis which developed in a patient being treated for seropositive rheumatoid arthritis with low dose methotrexate (5-7.5 mg weekly) for 8 years. The patient was successfully treated with itraconazole 200 mg daily for 6 months. This case adds to the growing evidence implicating low dose methotrexate with opportunistic infections and should heighten clinical awareness in patients on this treatment.

Aged↗

Mixed connective tissue disease with arterial thrombosis, antiphospholipid antibodies and heparin induced thrombocytopenia.

We report a patient with mixed connective tissue disease (MCTD) who presented with thrombosis of the right femoral artery in association with antiphospholipid antibodies (aPL). When treated surgically and with heparin prophylaxis, she developed heparin induced thrombocytopenia and thrombosis which necessitated amputation of a lower limb. Thus our patient developed 2 separate groups of autoantibodies associated with thrombotic events. Our case highlights an association between thrombosis, aPL and MCTD. Furthermore, it emphasizes a need for intensive monitoring when hypercoaguable individuals with connective tissue disorders are treated with heparin.

Adult↗

Postpsychotic depression and negative symptoms: an investigation of syndromal overlap.

The authors studied 46 patients with the operationally defined syndrome of postpsychotic depression following episodes of schizophrenia or schizoaffective disorder. Half of these patients were also found to satisfy criteria for negative symptoms. The patients with negative symptoms were rated as more severely ill on global measures, but there was only limited evidence that they were more depressed. Nevertheless, in a randomized double-blind trial of imipramine versus placebo as an adjunct to the fluphenazine decanoate and benztropine regimens of the patients with negative symptoms, the patients who received imipramine seemed to show more improvement.

Adolescent↗

Antidepressants in the treatment of post-psychotic depression in schizophrenia: drug interactions and other considerations.

Adjunctive imipramine has been found to be useful in the treatment of a substantial number of patients with syndromally defined post-psychotic depressions. This paper examines the clinical effects of the combined anticholinergic activity of imipramine, when added to ongoing fluphenazine decanoate/benztropine treatment, in such patients. Little additional anticholinergic impact of the imipramine was observable beyond that already attributable to the benztropine, and no significant relationships were found between a clinical measure of peripheral anticholinergic activity and either global clinical outcome or antidepressive efficacy. This paper also reports on the concentrations of imipramine and its metabolites in plasma under the conditions of this therapeutic trial. The changes in relative concentrations of imipramine and metabolites with time were consistent with the concept that fluphenazine competes with tricyclic metabolism. The relationship of plasma imipramine and desipramine to clinical improvement in this group of secondary depressions did not parallel previously reported relationships of these antidepressant molecules to clinical outcome in primary depressions.

Adult↗

Patterns of plasma imipramine-desipramine concentrations in patients receiving concomitant fluphenazine decanoate.

Plasma levels of imipramine and desipramine were monitored in a series of 13 patients with postpsychotic depressions who had a fixed dose of imipramine (150 mg/day) added to their clinically adjusted, stable dose of fluphenazine decanoate. Despite the potential for metabolic inhibition of the tricyclic drug by the neuroleptic drug, no relationship was found between the fluphenazine dose and the subsequent plasma concentrations of imipramine and desipramine. However, plasma antidepressant levels after 1 week at a low dose (50 mg/day) identified patients who later generated high plasma antidepressant levels at the full antidepressant dosage. The clinical implications of these observations are discussed.

Adult↗