Search PubMed⌕ Search

Biomedical subjects

F Fitzpatrick

Publications and source records attributed to F Fitzpatrick.

At least 19 recordsLinked to original sources
PubMed2005

The genetics of staphylococcal biofilm formation--will a greater understanding of pathogenesis lead to better management of device-related infection?

Staphylococcus epidermidis and Staphylococcus aureus are common causes of biofilm-mediated prosthetic device-related infection. The polysaccharide adhesion mechanism encoded by the ica operon is currently the best understood mediator of biofilm development, and represents an important virulence determinant. More recently, the contributions of other virulence regulators, including the global regulators agr, sarA and sigmaB, to the biofilm phenotype have also been investigated. Nevertheless, little has changed at the bedside; the clinical and laboratory diagnosis of device-related infection can be difficult, and biofilm resistance frequently results in failure of therapy. This review assesses the way in which advances in the understanding of biofilm genetics may impact on the clinical management of device-related infection.

Adhesins, Bacterial↗
PubMed2004

Genetic and phenotypic analysis of biofilm phenotypic variation in multiple Staphylococcus epidermidis isolates.

Production of biofilm in Staphylococcus epidermidis is mediated through enzymes produced by the four-gene operon ica and is subject to phenotypic variation. The purpose of these experiments was to investigate the regulation of ica and icaR transcription in phenotypic variants produced by multiple unrelated isolates of S. epidermidis. Ten isolates were chosen for the study, four of which contained IS256. IS256 mediates a reversible inactivation of ica in approximately 30 % of phenotypic variants. All ten strains produced at least two types of phenotypic variant (intermediate and smooth) in which biofilm formation was significantly impaired. Reversion studies indicated that all phenotypic variants were stable after overnight growth, but began to revert to other phenotypic forms after 5 days of incubation at 37 degrees C. ica transcriptional analysis was performed on phenotypic variants from three IS256-negative isolates; 1457, SE5 and 14765. This analysis demonstrated that ica transcription was significantly reduced in the majority of phenotypic variants, although two variants from SE5 and 1457 produced wild-type quantities of ica transcript. Analysis of seven additional phenotypic variants from SE5 revealed that ica expression was only reduced in three. Expression of icaR transcript was unaffected in all smooth phenotypic variants. Mutations within ica were identified in two SE5 variants with wild-type levels of ica transcription. It is concluded that mutation and transcriptional regulation of ica are the primary mechanisms that govern phenotypic variation of biofilm formation within IS256-negative S. epidermidis.

Bacterial Proteins↗
PubMed2004

An after-hours clinical liaison blood culture service--is it worth it?

The impact of clinical liaison on therapy for positive after-hours blood cultures was evaluated. Of 223 positive blood cultures, no change in management occurred in 164 (73%) cases: 115 positive cultures were regarded as contaminants, and 49 patients were receiving appropriate therapy already. The results of microscopy or culture altered the antimicrobial management of 59 (27%) patients: therapy was altered on the basis of microscopy for 33 patients, and was altered for 26 patients when culture results were available. In total, 94 doses of inappropriate antibiotics were avoided. The main benefit of after-hours blood cultures was that laboratory results were available a day earlier, facilitating timely initiation of appropriate therapy and infection control procedures.

Anti-Bacterial Agents↗
PubMed2004

The "silver-haired" general medical services patient. Clinical activity of the non-means tested over-70's during their first six months.

The objective was to examine the impact on general practice clinical activity of the granting of medical cards to all patients over 70 years of age on 01.07.01 under the General Medical Services (GMS) scheme. Retrospective case-control study. Chart review of 50 "new GMS" patients who received medical cards on 01.07.01 compared with 50 "old GMS" patients with means tested medical cards on this date. Single-handed mixed urban/rural general practice in Ireland. 1. Attendance rates. 2. Health status as measured by total number of chronic diseases, prevalence of hypertension, diabetes and cardiovascular disease. 3. Quality of preventive care comprising influenza and pneumococcal vaccine uptake rates; hypertension control; hyperlipidaemia control; level of screening activity for hypertension, diabetes, hyperlipidaemia, prostate specific antigen (among men) and smoking behaviour. Comparisons were made both before and after free GMS care for all between the "old GMS" and "new GMS" patient groups. Behaviour of the "new GMS" group was also compared, both before and after GMS eligibility. Prior to universal eligbility "old GMS" patients attended more often (p=0.0002), had more documented chronic illness (p=0.0002), consumed more medications (p=0.0002), were more likely to be diagnosed hypertensive (p=0.0336) and to have prostate specific antigen (PSA) measurement (men only) (p=0.048) than "new GMS" patients. Within the first 6 months of free GMS care for all, the "new GMS" patients attended significantly more often than before with the percentage of high consulters increasing from 24% to 52% (p=0.0039), took more medications (from 1.72 to 2.2), showed improvement in all quality of care parameters (with the exception of PSA screening which remained static) and had improved attendance for influenza 40% to 62% (p=0.0277) and pneumococcal vaccines 2% to 26% (p=0.00054). More "new GMS" patients were diagnosed as hypertensive (24% to 38%) to a prevalence no longer significantly different from the "old GMS" group. Free general practice care has impacted positively on this "new GMS" patient group of over 70's. Our data suggests that the low consultation rate of this group when fee paying may have resulted in less exposure to practice screening activities. The apparent better health status among this group may in fact be a façade masking undiagnosed chronic disease, notably hypertension.

Aged↗
PubMed2002

Environmental regulation of biofilm formation in intensive care unit isolates of Staphylococcus epidermidis.

Staphylococcus epidermidis is a common cause of prosthetic device-related infection in the intensive care unit (ICU). The environmentally regulated ica operon encodes a polysaccharide adhesin which is a key virulence determinant in the development of S. epidermidis biofilms. To evaluate the capacity of ICU S. epidermidis isolates to form biofilm, we measured biofilm production by 18 isolates associated with device-related infection and 20 contaminating isolates that were not associated with clinically diagnosed infection. Biofilm assays were performed in brain-heart infusion (BHI) medium and in BHI supplemented with salt, ethanol or subinhibitory tetracycline, all of which have the potential to promote biofilm formation. Polymerase chain reaction (PCR) was used to screen for the presence of the ica genes. A significant proportion of S. epidermidis strains associated with device-related infections (89%) were found to contain the ica locus compared with 50% of contaminating isolates (P = 0.01). However only four of 26 (15.3%) of all ica-positive isolates were biofilm-positive when grown in BHI medium, indicating that no significant association existed between the presence of the ica locus and biofilm-forming capacity, under standard growth conditions. In contrast the number of ica-positive isolates that were biofilm-positive under stress-inducing growth conditions or in the presence of subinhibitory tetracycline increased significantly to 73% (P = 0.02). These findings suggest that the presence of the ica locus alone is not sufficient for biofilm formation and that regulation of biofilm formation under altered growth conditions, which may exist in the in vivo environment, also plays a possible role in the pathogenesis of biomaterial-related S. epidermidis infections.

Biofilms↗
PubMed2001

Evaluation of ODS-AQ stationary phase for use in capillary electrochromatography.

The aim of this study was to evaluate the applicability of ODS-AQ packing material as a stationary phase in capillary electrochromatography (CEC). The electroosmotic flow created on an ODS-AQ stationary phase was measured at different mobile phase compositions and at different column temperatures. It was observed that the electroosmotic flow generated in the column increased by 50% when the temperature of the system was raised from 20 degrees C to 60 degrees C, while all other conditions were kept constant. The electroosmotic flow produced by the ODS-AQ stationary phase was found to be comparable to the flow generated in a column packed with Nucleosil bare-silica material. In addition, a set of polar compounds (D-lysergic acid diethylamide derivatives) was utilized to determine the influence of temperature and mobile phase composition on their chromatographic behavior on an ODS-AQ stationary phase in a CEC mode. A linear relationship between the solute retention factor and column temperatures was seen over the temperature range studied (20 degrees C to 60 degrees C). A quadratic function was used to describe the changes in the solute retention factors with variation of acetonitrile concentration in the mobile phase.

Chromatography, High Pressure Liquid↗
PubMed2001

Separation of peptides utilizing ultrahigh-temperature micellar electrokinetic chromatography.

The use of ultrahigh column temperatures, up to 110 degrees C, in micellar electrokinetic capillary chromatography was investigated. The number of plates generated per unit time increased from 0.22 to 12.8 plates/s for separations at 15 degrees C and 110 degrees C, respectively. Ultrahigh-temperature micellar electrokinetic capillary chromatography was used for the separation of cyclic undecapeptides (cyclosporins). A minimum resolution of 1.39 was calculated for a critical peak pair at 110 degrees C, which is more than a 50% increase over resolution generated at 40 degrees C. During a run time of more than 90 min at 110 degrees C and at pH 9.3, no sample degradation or solvent boiling was observed.

Acetonitriles↗
PubMed2000

High temperature and temperature programming in capillary electrochromatography.

In electrochromatography, solvent electrophoretic mobility and solute partitioning are temperature dependent processes. If temperature variations are controlled, solute selectivity and analysis times can be tailored. In this study the feasibility of temperature programming in capillary electrochromatography (CEC) was demonstrated using a reversed-phase CEC mode. The outcome of programmed separations was compared with isothermal, isocratic and isorheic (constant flow) separations. The combined effects of column temperature and mobile phase flow-rate changes during the separation run, resulted in up to a 50% reduction in the separation run time, without adversely affecting the quality of separation. For capillary electrochromatography, temperature programming may be a valuable alternative to solvent programming modes because of the great technical difficulties associated with carrying out solvent gradient elution.

Electrophoresis, Capillary↗
PubMed2000

Separation of D-lysergic acid diethylamide derivatives using micellar electrokinetic capillary chromatography.

By adjusting column temperature and applied electric field, a fast separation in micellar electrokinetic capillary chromatography was developed for the separation of D-lysergic acid diethylamide derivatives. A baseline separation of nine derivatives was accomplished with a run time of less than 12 min by utilizing elevated column temperature (60 degrees C) and an applied electric field of 387 V/cm. The number of plates generated per unit time for the separations completed at elevated temperatures was significantly higher when compared to separations at the same applied electric field but at lower temperatures (20 degrees C).

Chromatography, Micellar Electrokinetic Capillary↗
PubMed2000

A purpose built MRSA cohort unit.

The control of hospital-acquired infection, in particular methicillin-resistant Staphylococcus aureus (MRSA) remains a challenge. Our hospital has established a purpose built 11-bed cohort unit with on-site rehabilitation for care of patients colonized with MRSA, in an attempt to improve their quality of care. Prior to the opening of this unit a number of concerns were voiced and the aim of this study was to address these. First, to establish if patient cohorting reduces the likelihood of successful decolonization, second, to evaluate the risk of staff colonization, and finally to see if successful environmental control of MRSA is possible.A patient database was established detailing patient demographics, infection rates, eradication and reacquisition rates. Staff screening was performed weekly, at the start of a period of duty. Sixty environmental sites were screened before unit opening, at 48h, six weeks and at six months. There were 88 admissions in the first six months; 62 patients were colonized with MRSA, and 26 patients (10 surgical, 16 medical) had MRSA infections. Twenty-three of 88 patients (26%) were successfully decolonized, which compares favourably with an eradication rate of 20% for the rest of the hospital. Twenty staff members participated in weekly screening. Five staff members colonized with MRSA were detected and all were successfully decolonized. Environmental control was achieved with a combination of a daily detergent clean and a once weekly clean with phenolic disinfectant. Our preliminary data suggest that, despite cohorting patients colonized with MRSA, with proper education and supervised cleaning protocols, it is possible to control environmental MRSA load, successfully decolonize patients and limit the risk of staff colonization.

Carrier State↗
PubMed1999

High rate of human T lymphotropic virus type IIa infection in HIV type 1-infected intravenous drug abusers in Ireland.

Serological and molecular analyses of a cohort of HIV-1-infected intravenous drug abusers (IVDAs) (n = 103) in Dublin, Ireland have demonstrated that 15 of 103 (14.6%) were infected with HTLV-II, which is the highest infection rate yet recorded for any European country. Restriction fragment length polymorphism (RFLP) analysis of the env region of the provirus demonstrated that the infection involved only the HTLV-IIa subtype; the HTLV-IIb subtype was not detected. Phylogenetic analysis of the nucleotide sequences of the long terminal repeat (LTR) confirmed infection with the HTLV-IIa subtype, and demonstrated that the viruses clustered closely with HTLV-IIa isolates from North American IVDAs. Previous observations that IVDAs in southern Europe, specifically Spain and Italy, appear to be infected predominantly with the HTLV-IIb subtype, along with the present report and evidence that IVDAs in Sweden are infected with the HTLV-IIa subtype, suggest different origins of HTLV-II infection in Europe.

Adult↗
PubMed1996

Inhibition of 5-lipoxygenase-activating protein (FLAP) reduces pulmonary vascular reactivity and pulmonary hypertension in hypoxic rats.

Chronically elevated shear stress and inflammation are important in hypertensive lung vessel remodeling. We postulate that 5-lipoxygenase (5-LO) is a molecular determinant of these processes. Immunohistology localized the 5-LO to macrophages of normal and chronically hypoxic rat lungs and also to vascular endothelial cells in chronically hypoxic lungs only. In situ hybridization of normal and chronically hypoxic lungs demonstrated that 5-LO mRNA is expressed in macrophages. Rats hypoxic for 4 wk-developed pulmonary hypertension increased translocation of the lung 5-LO from the cytosol to the membrane fraction and increased levels of lung tissue 5-lipoxygenase-activating protein (FLAP). A FLAP ligand, 3-[l-(4-chlorobenzyl)-3-t-butyl-thio-t-isopropylindol-2-yl]-2,2- dimethylpropanoic acid (MK-886), inhibited the acute angiotensin II and hypoxia-induced pulmonary vasoconstriction in vitro and the development of chronic hypoxic pulmonary hypertension in rats in vivo. Mice bred with the deletion of the 5-LO enzyme (5-LO knockout) developed less right heart hypertrophy than age-matched 5-LO competent mice. Our results support the hypothesis that the 5-LO is involved in lung vascular tone regulation and in the development of chronic pulmonary hypertension in hypoxic rodent models.

5-Lipoxygenase-Activating Proteins↗