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Biomedical subjects

J M Courtney

Publications and source records attributed to J M Courtney.

At least 19 recordsLinked to original sources
PubMed2004

Clinical outcome of Burkholderia cepacia complex infection in cystic fibrosis adults.

BACKGROUND: The Burkholderia cepacia complex (BCC) is one of the most important groups of organisms infecting cystic fibrosis (CF) patients. The aim of the study was to examine how infection with BCC affects clinical outcome. METHODS: Nineteen CF adults infected with BCC and 19 controls infected with Pseudomonas aeruginosa were studied over a 4-year period. The best forced expiratory volume in 1 s (FEV(1)) and body mass index (BMI) for each year were recorded and annual rate of decline calculated. RESULTS: The BCC infected group displayed a significantly greater reduction of FEV(1) and BMI compared to the P. aeruginosa infected group (p=0.001 and p=0.009, respectively). Sixteen patients infected with a single Burkholderia cenocepacia strain had a significantly greater rate of FEV(1) decline compared to those infected with Burkholderia multivorans (n=3) or P. aeruginosa (p=0.01 and p<0.0001, respectively). The rate of BMI decline was significantly greater in patients infected with B. cenocepacia compared to those with P. aeruginosa (p=0.007), but not significantly different in those with B. multivorans (p=0.29). CONCLUSION: BCC infection is associated with an accelerated decline in pulmonary function and BMI. Infection with a single B. cenocepacia strain was associated with a more rapid decline in lung function than those infected with either B. multivorans or P. aeruginosa.

Adult↗
PubMed2004

Cytokines and inflammatory mediators in cystic fibrosis.

Airway disease in cystic fibrosis (CF) is characterised by a continuous cycle of chronic infection and inflammation dominated by a neutrophilic infiltrate. This inflammation is characterised by an increased production of pro-inflammatory cytokines in the lung. The relationship between the abnormal CFTR gene product and the development of inflammation and progression of lung disease in CF is not fully understood. This review article studied the mechanisms of pulmonary inflammation in CF, the profiles of cytokines and inflammatory mediators in the lung in CF, the mechanisms that predispose to chronic Pseudomonas aeruginosa infection, cytokine involvement in diseases other than CF and reviewed current therapeutic strategies for CF. Imbalances of cytokine secretion are now better understood due to recent advances in understanding CF at a molecular level and it is increasingly thought that the normal inflammatory process is deranged in CF early in the course of the disease and may occur in the absence of detectable infection. However, the relationship between this unbalanced cytokine production, the mutations in CFTR and its actual consequence for pathogenesis need further investigation.

Anti-Inflammatory Agents↗
PubMed2003

Blood response to plasticized poly(vinyl chloride): dependence of fibrinogen adsorption on plasticizer selection and surface plasticizer level.

The high level of plasticizer in plasticized poly(vinyl chloride) (PVC) ensures that plasticizer selection has an important influence on the suitability of PVC to function in blood-contacting applications. In this study, three types of plasticized PVC in sheet form, with di-(2-ethylhexyl)phthalate (DEHP), tri-(2-ethylhexyl)trimellitate (TEHTM) and n-butyryltri-n-hexyl citrate (BTHC) as plasticizer, were selected for assessment and single solute fibrinogen adsorption was utilized as an initial index of interactions with blood components. Fibrinogen adsorption behavior shows a strong dependence on the plasticizer selection, plasticizer level at the surface and the adsorption conditions, such as adsorption time and fibrinogen solution concentration. Results indicate that BTHC plasticized PVC possesses the lowest adsorption capacity in the three types of plasticized PVC, while TEHTM plasticized PVC seems to have the strongest reactivity in certain fibrinogen solution concentrations. The alteration of surface plasticizer level was achieved by a methanol-cleaning treatment with a variety of cleaning times and the fibrinogen adsorption on plasticized PVC decreases with the reduction of surface plasticizer level. The migration behavior of two phthalate esters (DEHP and TEHTM) was evaluated using UV-Spectrophotometer to determine the plasticizer level at the surfaces. In addition, the fibrinogen adsorption mechanism was examined with Freundlich adsorption modeling.

Journal Article↗
PubMed2003

Modification of polymer surfaces: optimization of approaches.

Modification of polymer surfaces to achieve a surface with enhanced compatibility is an important means of obtaining improved biomaterials. Techniques are available for altering the hydrophilicity or charge of a surface, attaching macromolecules or attempting to resemble cell membranes. Relevant to the clinical success of a modified surface is the modification procedure and a procedure based on incorporation as opposed to surface treatment has potential advantages. The modification of plasticized vinyl chloride (PVC) by the incorporation of cyclodextrins is described. In comparison to unmodified PVC controls, cyclodextrin incorporation reduced fibrinogen adsorption, with the extent of reduction dependent on the type and quantity of cyclodextrin incorporated.

Adsorption↗
PubMed2001

Multisorbent plasma perfusion in fulminant hepatic failure: effects of duration and frequency of treatment in rats with grade III hepatic coma.

Using the model of galactosamine-induced fulminant hepatic failure in the rat, the effects of multisorbent plasma perfusion over Asahi uncoated spherical charcoal, Plasorba (BR-350) resin, and an endotoxin removing adsorbent (polymyxin B-sepharose) were determined in Grade III hepatic coma animals by studying survival as influenced by timing, duration, and frequency of treatment. The effects of treatment on liver cell proliferation and endotoxin removal also were examined. The results demonstrate that duration and frequency of treatment are major contributing factors in the successful application of nonbiological membrane-based multisorbent liver support systems. Examination of the regenerative activity in the liver indicates an enhanced proliferative response following multisorbent plasma perfusion compared with untreated fulminant hepatic failure (FHF) paired controls. Utilizing an endotoxin removal adsorbent alone, a marked reduction in systemic levels of endotoxin in FHF was demonstrated compared with nonperfused FHF paired controls. Despite current emphasis on bioartificial liver support systems, plasma purification by multisorbent systems offers a simple method for the removal of circulating toxic metabolites in general together with specific toxin removal.

Animals↗
PubMed2000

In vitro investigation of the blood response to medical grade PVC and the effect of heparin on the blood response.

This paper reports the results of an investigation into the blood response of polymers in vitro, using non-anticoagulated and heparinised blood and plasma. The materials studied were regenerated cellulose, (Cuprophan), an acrylonitrile-allyl sulphonate copolymer (AN69S), and medical grade polyvinyl chloride plasticised with di-2-ethyl-hexyl-phthalate (PVC/DEHP). Blood-material or plasma-material contact was achieved using a parallel plate flow cell, and C3a generation and FXII-like activity measured. The results of the study with non-anticoagulated human blood show that PVC/DEHP is a high complement activator. C3a concentration in the blood was higher after contact with PVC/DEHP than after contact with regenerated cellulose. The introduction of heparin in the blood induced complex alterations in the blood response. C3a generation could be elevated, decreased, or remain the same, depending on the material. The FXII-like activity on the surface of the PVC/DEHP after contact with plasma was also higher than the other two polymers. The introduction of heparin could increase or decrease FXII-like activity, depending on material. The patterns of response obtained with non-anticoagulated blood in vitro for AN69S and Cuprophan bore a strong resemblance with patterns of response obtained in the clinic, whereas those obtained with heparinised blood in vitro did not.

Acrylic Resins↗
PubMed1999

Blood interactions with plasticized poly(vinyl chloride): relevance of plasticizer selection.

An investigation has been made of blood interactions with plasticized poly(vinyl chloride) (PVC) biomaterials in tubular form, taking into account the influence on the blood response of the polymer, antithrombotic agent, blood condition and test procedure. In vitro and ex vivo procedures were used to achieve a comparison between PVC plasticized with di- (2-ethylhexyl)phthalate (DEHP) and with tri-(2-ethylhexyl)trimellitate (TEHTM). The blood response was monitored in terms of the measurement of fibrinogen adsorption capacity, thrombin-antithrombin III complex (TAT) and the complement component C3a. Surface characterization of the polymers was performed by X-ray photoelectron spectroscopy (XPS). The data obtained indicate that in comparison with DEHP-PVC, there is a higher reactivity for TEHTM-PVC, which correlates with the plasticizer distribution at the polymer surface.

Journal Article↗
PubMed1999

Influence on blood of plasticized polyvinyl chloride: significance of the plasticizer.

An investigation has been made of the significance of the level of the plasticizer di-(2-ethylhexyl)phthalate at the surface of plasticized polyvinyl chloride for interactions with blood components. Plasticized polyvinyl chloride before and after treatment with methanol to reduce the plasticizer surface level was assessed in terms of fibrinogen and albumin adsorption with unplasticized polyvinyl chloride acting as a control. As the plasticizer surface level decreased, fibrinogen adsorption decreased almost linearly while albumin adsorption increased initially before decreasing slightly. The investigation indicates that reduction in the amount of plasticizer at the surface improves the blood compatibility of plasticized polyvinyl chloride, and the influence on blood is due primarily to the plasticizer rather than the polyvinyl chloride itself.

Adsorption↗
PubMed1999

Examination of particulate macroporous hydrogels in an extracorporeal rat haemoperfusion model.

A series of macroporous hydrogels has been synthesized, selected from a range of such materials in which the presence of functional groups has been shown to produce sorbent properties with respect to molecules having clinical significance in the field of liver support. The use of freeze thaw polymerization, together with inverse suspension polymerization in hexane, or in brine, enables macroporous beads ranging in size from 150 to 2000 microm, to be prepared from functional monomers exhibiting a range of chemical functionalities and aqueous solubilities. In order to investigate the behaviour of these rigid porous hydrophilic substrates in haemoperfusion, a rat model was used to explore various aspects of whole blood response. The materials were incorporated into an extracorporeal circuit linking the right carotid artery and left jugular vein of male Sprague-Dawley rats. Erythrocyte, leucocyte and platelet levels were monitored over a 240 min haemoperfusion period. The most significant observation is that, apart from the strongly acidic polyacrylic acid substrate. matrix chemistry has relatively little effect on leucocyte or platelet response. The most important factors appear to be surface area, pore size and surface rugosity, which do produce measurable, but not dramatic differences. This is encouraging for future work, since these variables may be manipulated by polymerization conditions.

Acrylates↗
PubMed1998

Complement activation by cellulose: investigation of the effects of time, area, flow rate, shear rate and temperature on C3a generation in vitro, using a parallel plate flow cell.

The development and utilization of a parallel plate flow system to study the blood response to flat sheet biomaterials, is described. Unlike most other parallel plate flow systems, which have been used to study cellular interactions with biomaterials, the controlled flow test cell described below employs the test materials on both sides of the channel through which the blood flows. The flow cell is used to conduct an investigation into the in vitro generation of C3a by a regenerated cellulose membrane, Cuprophan. The effects of experimental variables such as temperature, blood flow rate, contact area and wall shear rate on C3a generation by Cuprophan were studied. The results show that C3a generation by Cuprophan is lower at 12 degrees C than at 22 degrees C, which is in turn lower than C3a generation at 37 degrees C. Furthermore, a decrease in contact area, and increase in wall shear rate and blood flow rate, can produce a decrease in C3a concentration.

Journal Article↗
PubMed1998

Artificial cell containing superoxide dismutase--selection of folding aids for stabilisation of SOD.

Superoxide dismutase (abbreviated as SOD) has been vigorously studied in the fields of radical chemistry and related life science. One of practical problems is how to keep its activity in certain adverse conditions causing denaturation. Artificial cell containing SOD can be prepared by polymer encapsulation or nanocapsulation which has been found to be effective to improve the stability of SOD. For construction of an ideal artificial cell system, some folding aids or aggregation inhibitors were utilised to enhance SOD stability. In this study, three groups of biopolymers are selected as folding aids or aggregation inhibitors for stabilisation of SOD, i.e. albumin, carbohydrates and glycoproteins. Results indicate that the thermostability of SOD is affected by different sort of albumin while some carbohydrates such as cyclodextrins are found to be able to enhance SOD stability. In addition, it is firstly found that selected glycoproteins such as alpha-macroglobulin and ovalbumin are several types of effective folding aids for stabilisation of SOD. They can protect SOD against denaturation even at very high temperature(over 100 degrees C). The stability was tested by the measurement of SOD activity loss using autooxidation method in different adverse conditions such as high temperature, extreme pH medium, proteolytic hydrolysis and long shelf life storage. The possible stabilisation mechanism of using cyclodextrins and glycoproteins as folding aids were discussed.

Albumins↗
PubMed1997

Ex vivo complement protein adsorption on positively and negatively charged cellulose dialyser membranes.

An ex vivo test system was used to measure complement protein C3 and factor B adsorption onto small dialyser modules made from regenerated and modified cellulosic hollow fibre membranes in which positive diethylaminoethyl (DEAE) or negative carboxymethyl (CM) groups were introduced into the cellulose matrix. The extracorporeal system, which included test-dialysers and the dialysis environment, allowed the use of labelled proteins without contaminating the blood donors which were connected in an open-loop fashion to the extracorporeal test system. The modules were removed at selected time points from the extracorporeal system for radioactivity counting. The results were used to evaluate the mechanisms involved in complement reactions to foreign surfaces. The system therefore allowed the analysis of complement protein adsorption occurring in the dialyser modules and its relationship to the complement generation rate in the extracorporeal system to be evaluated. It was possible to demonstrate that significant complement C3 and factor B adsorption occurred in the test modules made of cellulosic membranes. Complement adsorption as a function of the pH and the release reaction of the adsorbed C3 and factor B after membrane blood perfusion were therefore found to be variable according to the cellulosic membrane type and the presence of positive or negative charged groups within the cellulose matrix. The data obtained from the ex vivo model therefore provided additional evidence on the discussion of the mechanisms involved in the increased complement activation by regenerated cellulose and in its attenuation by DEAE- or CM-modified cellulose.

Journal Article↗
PubMed1996

Determination of contact phase activation by the measurement of the activity of supernatant and membrane surface-adsorbed factor XII (FXII): its relevance as a useful parameter for the in vitro assessment of haemodialysis membranes.

We investigated hemodialysis membrane biocompatibility with respect to contact phase activation by determination of FXII-like activity (FXIIA) on the membrane surface and in the supernatant phase, during plasma contact with various hemodialysis membranes using an in vitro incubation test cell. The results were compared to the influence of these membranes on the activation of purified FXII. A time course for the generation of activated FXII using purified FXII solution at physiologic concentrations on two similar negatively charged polymers was performed. The membranes assessed were regenerated cellulose (Cuprophan; Akzo Faser AG, Germany), modified cellulosic (Hemophan; Akzo Faser AG), acrylonitrile-sodium methallyl copolymer-based membrane AN69S (Hospal, France), and SPAN, a new polyacrylonitrile-based copolymer (akzo Nobel AG). The plasma FXIIA at the membranes surface was significantly different between the membranes, while the supernatant phase FXIIA exhibited no significant differences. In contrast, activation of purified FXII in a plasma-free system with respect to supernatant activity indicated significant differences between the materials. A similar finding for the membrane-bound factor XIIA was also observed when purified factor XII was used. The membrane-bound FXIIA values observed in the plasma system containing heparin were significantly greater than in citrated plasma. This demonstrated the strong influence of heparin and the interaction of other plasma components to the membrane surface on the activation of contact phase of coagulation.

Adsorption↗
PubMed1996

Sensitivity of cell lines to mitomycin C.

OBJECTIVES: To determine the effect of pH on the cytotoxicity of mitomycin C on a wide range of established cell lines. MATERIALS AND METHODS: Cultures of three human tumour cell lines, including two bladder carcinomas and one renal adenocarcinoma, and two mouse cell lines were treated with mitomycin C (concentration range 320 pM-50 microM) at a range of pH (5.8-7.8) for 2 h. The cytotoxicity of mitomycin C over this range was determined using a tetrazolium-dye-based microtitration assay. RESULTS: The cytotoxicity of mitomycin C was significantly greater (confidence level > or = 95%) in acidic conditions (pH 5.8-6.0) than in neutral to alkaline pH (7.2-7.8) for three of the five cell lines. The same trend, although less marked, also occurred in the other two cell lines. CONCLUSION: The cytotoxicity of mitomycin C was greater under acidic conditions for all these cell lines confirming that the activity of mitomycin C depends on pH and suggesting that the pH of the vehicle used for intravesical chemotherapy may be an important factor in the successful treatment of bladder carcinomas. The modification of pH by urine may explain some of the variation in success rates among patients treated intravesically with mitomycin C.

Adenocarcinoma↗
PubMed1996

The influence of biomaterials on inflammatory responses to cardiopulmonary bypass.

The nature of cardiopulmonary bypass and the complexity of the inflammatory response make the detection and interpretation of a biomaterial influence difficult. However, if mediation of the inflammatory response is considered to be an appropriate clinical goal, alteration to the biomaterial influence merits further investigation.

Biocompatible Materials↗
PubMed1996

In vitro blood compatibility evaluation of hollow fibre membrane using a controlled flow system: a comparative study.

A procedure has been established for the in vitro assessment of hollow fibre haemodialysis membranes. A 30 ml syringe containing 20 ml of fresh non-anticoagulated blood was mounted onto a non-pulsatile syringe pump and blood was perfused through minimodules constructed from 80 fibres retrieved from Cuprophan (Baxter ST15), cellulose acetate (M57-12, JMS Co Ltd, Hiroshima, Japan), and AN69HF (Filtral 20, Hospal, France) dialysers. Samples were collected before perfusion, 3, 6, 9 and 12 minutes. The modules were clamped vertically to minimise the effect of red cell pooling and the dialysate compartment was filled with 0.9% saline to minimise ultrafiltration. After sample processing, complement C3a, thrombin-antithrombin III complexes, prothrombin F1 + 2, and factor XII-like activity were evaluated. The results indicated that the system could discriminate between the membranes evaluated and therefore was a relevant procedure for the assessment of hollow fibre haemodialysis membranes.

Antithrombin III↗