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Biomedical subjects

B P Murphy

Publications and source records attributed to B P Murphy.

At least 19 recordsLinked to original sources

Persistent lactic acidosis in neonatal hypoxic-ischaemic encephalopathy correlates with EEG grade and electrographic seizure burden.

BACKGROUND: Predicting at birth which infants with perinatal hypoxic-ischaemic injury will progress to significant encephalopathy remains a challenge. OBJECTIVE: To determine whether lactic acidosis at birth in asphyxiated neonates could predict the grade of EEG encephalopathy by examining the relationship between time taken for the normalisation of lactate, severity of encephalopathy and seizure burden. METHODS: Continuous early video-EEG monitoring was performed in babies at risk for hypoxic-ischaemic encephalopathy. Encephalopathy was graded from the EEG data. Total seizure burden (seconds) was calculated for each baby. Initial blood gas measurements of pH, base deficit and lactate were taken within 30 minutes of delivery. Time to normal serum lactate was determined in hours from birth for each infant. RESULTS: All 50 term infants had raised initial serum lactate (median (lower, upper quartiles) 11.7 (10.2, 14.9)). There were no significant differences between the initial serum lactate, pH and base deficit in infants with normal/mildly abnormal (n = 24), moderately abnormal (n = 14), severely abnormal (n = 5) and inactive EEGs (n = 7). Time to normal lactate varied significantly with EEG grade (median (lower, upper quartile) 6.0 (4.1, 9.5) for mild/normal EEG, 13.5 (6.8, 23.5) moderate EEG, 41.5 (30.0, 55.5) severe group, 12.0 (8.1, 21.5) inactive group; p<0.001). Time to normal lactate correlated significantly with EEG seizure burden (seconds; R = 0.446, p = 0.002). Mean (SD) time to normal lactate was 10.0 (7.2) hours in infants who did not have seizures and 27.3 (19.0) hours in the 13 infants with electrographic seizures (p = 0.002). CONCLUSIONS: Serum lactate levels in the first 30 minutes of life do not predict the severity of the ensuing encephalopathy. In contrast, sustained lactic acidosis is associated with severe encephalopathy on EEG and correlates with seizure burden.

Acidosis, Lactic↗

The influence of grain size on the ductility of micro-scale stainless steel stent struts.

Vascular stents are used to restore blood flow in stenotic arteries, and at present the implantation of a stent is the preferred revascularisation method for treating coronary artery disease, as the introduction of drug eluting stents (DESs) has lead to a significant improvement in the clinical outcome of coronary stenting. However the mechanical limits of stents are being tested when they are deployed in severe cases. In this study we aimed to show (by a combination of experimental tests and crystal plasticity finite element models) that the ductility of stainless steel stent struts can be increased by optimising the grain structure within micro-scale stainless steel stent struts. The results of the study show that within the specimen size range 55 to 190 microm ductility was not dependent on the size of the stent strut when the grain size maximised. For values of the ratio of cross sectional area to characteristic grain length less than 1,000, ductility was at a minimum irrespective of specimen size. However, when the ratio of cross sectional area to characteristic grain length becomes greater than 1,000 an improvement in ductility occurs, reaching a plateau when the ratio approaches a value characteristic of bulk material properties. In conclusion the ductility of micro-scale stainless steel stent struts is sensitive to microstructure and can be improved by reducing the grain size.

Biocompatible Materials↗

Genomic comparisons of Salmonella enterica serovar Dublin, Agona, and Typhimurium strains recently isolated from milk filters and bovine samples from Ireland, using a Salmonella microarray.

Salmonella-induced enterocolitis is the leading food-borne illness with a lethal outcome and causes millions of cases of gastroenteritis each year. We examined genomic variation among 12 environmental, veterinary, and clinical Salmonella enterica serovar Dublin, Agona, and Typhimurium strains isolated in Ireland between 2000 and 2003, as well as two clinical isolates from Canada and four archival isolates, which belonged to serovars Dublin and Agona. Using DNA-DNA hybridization to a microarray consisting of most of the predicted protein-encoding sequences of the S. enterica serovar Typhimurium LT2 genome, we identified a number of genomic regions that were absent in one or more serovars. The 34 genomic regions encoded proteins involved in sugar metabolism, transport, fimbrial and phage biogenesis, and transcriptional regulation, as well as inner and outer membrane-associated proteins. Two of the four prophages identified in strain LT2, prophages Gifsy-1 and Gifsy-2, were present in all six serovar Typhimurium strains examined. Prophage Fels-1 was absent from all 18 isolates examined, and Fels-2 was completely absent from the serovar Typhimurium isolates and the Salmonella Reference Collection B serovar Dublin strain Du2. All five Salmonella pathogenicity islands were present in all isolates. Plasmid pSLT was absent from all serovar Agona isolates, and only homologues of the spv genes were present in eight of the nine serovar Dublin strains. Only limited intraserovar diversity was found among the nine serovar Dublin, three serovar Agona, and six serovar Typhimurium isolates examined even though these isolates had extensive geographic, temporal, and source differences.

Animals↗

Coronary stent strut size dependent stress-strain response investigated using micromechanical finite element models.

Cardiovascular stents are metal scaffolds that are used in the treatment of atherosclerosis. These devices are typically composed of very thin struts (< or = 100 microm thickness, for coronary applications). At this size-scale the question arises as to the suitability of using bulk material properties in stent design. This paper investigates the use of finite element analysis to predict the mechanical failure of stent struts, typical of the strut size used in coronary stents. 316 L stainless steel in uniaxial loading was considered. To accurately represent the constitutive behavior of the material at this size-scale, a computational micromechanics approach was taken involving an explicit representation of the grain structure in the steel struts, and the use of crystal plasticity theory to represent the constitutive behavior of the individual grains. The development of the finite element models is discussed and results are presented for the predictions of tensile mechanical behavior as a function of strut thickness. The results showed that using this modelling approach, a size effect, already seen experimentally, is produced. This has significant implications for stent design, especially in the context of the desire to produce smaller stents for small bore neurovascular and peripheral artery applications.

Biocompatible Materials↗

Mining the microbiota of the neonatal gastrointestinal tract for conjugated linoleic acid-producing bifidobacteria.

This study was designed to isolate different strains of the genus Bifidobacterium from the fecal material of neonates and to assess their ability to produce the cis-9, trans-11 conjugated linoleic acid (CLA) isomer from free linoleic acid. Fecal material was collected from 24 neonates aged between 3 days and 2 months in a neonatal unit (Erinville Hospital, Cork, Ireland). A total of 46 isolates from six neonates were confirmed to be Bifidobacterium species based on a combination of the fructose-6-phosphate phosphoketolase assay, RAPD [random(ly) amplified polymorphic DNA] PCR, pulsed-field gel electrophoresis (PFGE), and partial 16S ribosomal DNA sequencing. Interestingly, only 1 of the 11 neonates that had received antibiotic treatment produced bifidobacteria. PFGE after genomic digestion with the restriction enzyme XbaI demonstrated that the bifidobacteria population displayed considerable genomic diversity among the neonates, with each containing between one and five dominant strains, whereas 11 different macro restriction patterns were obtained. In only one case did a single strain appear in two neonates. All genetically distinct strains were then screened for CLA production after 72 h of incubation with 0.5 mg of free linoleic acid ml(-1) by using gas-liquid chromatography. The most efficient producers belonged to the species Bifidobacterium breve, of which two different strains converted 29 and 27% of the free linoleic acid to the cis-9, trans-11 isomer per microgram of dry cells, respectively. In addition, a strain of Bifidobacterium bifidum showed a conversion rate of 18%/microg dry cells. The ability of some Bifidobacterium strains to produce CLA could be another human health-promoting property linked to members of the genus, given that this metabolite has demonstrated anticarcinogenic activity in vitro and in vivo.

Aldehyde-Lyases↗

Comparison of three manual ventilation devices using an intubated mannequin.

OBJECTIVE: To compare three devices for manual neonatal ventilation. DESIGN: Participants performed a two minute period of ventilation using a self inflating device, an anaesthesia bag with attached manometer, and a Neopuff device. An intubated neonatal mannequin, approximating a 1 kg infant with functional lungs, was used for the study. Target ventilation variables included a rate of 40 breaths per minute, peak inspiratory pressure (PIP) of 20 cm H2O, and positive end expiratory pressure (PEEP) of 4 cm H2O. The circuit was attached to a laptop computer for data recording. RESULTS: Thirty five participants were enrolled, including consultant neonatologists, paediatricians, and anaesthetists, paediatric and anaesthetic registrars, and neonatal nurses. The maximum PIP recorded using the self inflating bag, anaesthetic bag, and Neopuff device were 75.9, 35.5, and 22.4 cm H2O respectively. There were significant differences between the devices for mean PIP (30.7, 18.1, and 20.1 cm H2O), mean PEEP (0.2, 2.8, and 4.4 cm H2O), mean airway pressure (7.6, 8.5, and 10.9 cm H2O), % total breaths < or = 21 cm H2O PIP (39%, 92%, and 98%), and % total breaths > or = 30 cm H2O PIP (45%, 0, and 0). There was no difference between doctors and allied health professionals for the variables examined. CONCLUSION: The anaesthetic bag with manometer and Neopuff device both facilitate accurate and reproducible manual ventilation. Self inflating devices without modifications are not as consistent by comparison and should incorporate a manometer and a PEEP device, particularly when used for resuscitation of very low birthweight infants.

Allied Health Personnel↗

Multi-axial fatigue failure of orthopedic bone cement - experiments with tubular specimens.

Bone cement is subjected to multi-axial cyclic loading when used to fixate orthopedic prostheses for joint arthroplasty. In this study, tubular specimens of poly(methylmethacrylate) (PMMA) bone cement are subjected to internal pressure and cyclic axial loading to ascertain the influence of multi-axial loading on fatigue life. As expected, it was found that the probability of survival of specimens under multi-axial loading was very much reduced relative to specimens loaded uniaxially. Furthermore, the variability of the fatigue life was increased by multi-axial loading. In conclusion, the results point to the importance of characterizing the behavior of bone cements under the multi-axial fatigue experienced in vivo, and of the importance of accounting for the multi-axial stress state when predicting implant longevity.

Journal Article↗

The stress-strain behavior of coronary stent struts is size dependent.

Coronary stents are used to re-establish the vascular lumen and flow conditions within the coronary arteries; the typical thickness of a stent strut is 100 microm, and average grain sizes of approximately 25 microm exist in stainless steel stents. The purpose of this study is to investigate the effect of strut size on the stress strain behavior of 316 L stainless steel. Other materials have shown a size dependence at the micron size scale; however, at present there are no studies that show a material property size dependence in coronary stents. Electropolished stainless steel stent struts within the size range of 60-500 microm were tensile tested. The results showed that within the size range of coronary stent struts a size dependent stress-strain relationship is required to describe the material. Finite element models of the final phase of fracture, i.e., void growth models, explained partially the reason for this size effect. This study demonstrated that a size based stress-strain relationship must be used to describe the tensile behavior material of 316 L stainless steel at the size scale of coronary stent struts.

Arteries↗

The relationship between stress, porosity, and nonlinear damage accumulation in acrylic bone cement.

The long-term survival of cemented hip replacements depends on the ability of the cemented fixation to resist fatigue damage. Damage has been assumed to accumulate linearly (Miner's law) even though it is unlikely to be the case in such a porous brittle material. This study addresses the nonlinear stress-dependent nature of fatigue damage accumulation in acrylic bone cement. Specimens were subjected to a zero-to-tension fatigue load in water at 37 degrees C. A total of 15 specimens were tested, i.e., five specimens at each of three stress levels. The specimens were cyclically loaded to a certain fraction of their fatigue lives and the amount of microcracking present at that time was quantified by counting each crack and measuring its length. This procedure was repeated until the specimen failed. A total of 801 cracks formed in the 15 specimens. All cracks were found to initiate at pores. Crack propagation directions were distributed normally about the direction perpendicular to the applied load at the lower stress levels, but at higher stress, the distribution tended to be broader. At higher stresses, more cracks were produced per pore. The damage accumulation process in acrylic bone cement was found to be nonlinear with the degree of nonlinearity increasing with stress. Furthermore, great variability was found which was attributed to the differences in porosity between specimens. A power law equation is given which describes the predicted relationship between damage accumulation and number of loading cycles as a function of the stress level.

Bone Cements↗

Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome.

OBJECTIVE: To investigate the natural history and predictors of outcome of posthaemorrhagic ventriculomegaly in the very low birthweight (VLBW) infant. METHODS: All VLBW infants admitted between September 1994 and September 1997 to the neonatal intensive care units of Brigham and Women's Hospital (Boston), Children's Hospital (Boston), and Christchurch Women's Hospital (New Zealand) with germinal matrix intraventricular haemorrhage (IVH) were identified. All charts and ultrasound scans were reviewed to define the natural history and perinatal and/or postnatal factors of value in prediction of the course of posthaemorrhagic ventriculomegaly. Progressive ventricular dilatation (PVD) was defined from the results of serial cranial ultrasound scans. RESULTS: A total of 248 VLBW infants had evidence of IVH (22% of all VLBW infants, mean (SD) gestational age 26.8 (2.6) weeks). A quarter of the infants exhibited PVD. Spontaneous arrest of PVD occurred without treatment in 38% of infants with PVD. Of the remaining 62% with persistent PVD, 48% received non-surgical treatment only (pharmacological and/or drainage of cerebrospinal fluid by serial lumbar punctures), 34% received surgical treatment with insertion of a ventriculoperitoneal reservoir and/or shunt, and 18% died. The development of PVD after IVH and adverse short term outcome, such as the requirement for surgery, were predicted most strongly by the severity of IVH. CONCLUSIONS: These data reflect the natural history of PVD in the 1990s and show that, despite a slight reduction in its overall incidence, there appears to be a more aggressive course, with appreciable mortality and morbidity in the extremely premature infant. The major predictor of adverse short term outcome, defined as death or need for surgical intervention, was the severity of IVH. These findings may be valuable for the management of very small premature infants.

Boston↗

Line scan diffusion tensor MRI of the cervical spinal cord in preterm infants.

Line scan diffusion tensor magenetic resonance imaging (DT-MRI) of the cervical spinal cord was demonstrated in vivo for unsedated preterm (gestational age 24-30 weeks at birth), very low birthweight (birthweight 620-1300 g) infants at postmenstrual ages from 29-40 weeks. Scalar invariant measures of diffusion [apparent diffusion coefficient (ADC) and relative anisotropy (RA)] determined from a cervical cord region of interest in each case are reported, characterizing the maturational status of the normal third trimester and newborn spinal cord. Mean ADC of 11 infants was 1.2 +/- 0.1 microm(2)/msec and the mean RA was 24.3 +/- 4.9%. Normal infant cord neural fiber tract morphology was visualized using a mapping of the predominant diffusion tensor eigenvector. Potential clinical applications of line scan DT-MRI of the spinal cord of preterm and term newborns for assessment of spinal cord injury are discussed. J. Magn. Reson. Imaging 2001;13:949-953.

Adult↗

Impaired cerebral cortical gray matter growth after treatment with dexamethasone for neonatal chronic lung disease.

OBJECTIVE: The specific aim of this study was to quantify at term the influence of postnatal systemic dexamethasone treatment for neonatal chronic lung disease on subsequent brain growth and development in premature infants without evidence of severe intraventricular hemorrhage or white matter injury. METHODS: Eighteen premature (23 to 31 weeks) infants, 7 treated with dexamethasone and 11 not treated, were studied at term, ie, 38 to 41 postconceptional weeks, by an advanced quantitative volumetric 3-dimensional magnetic resonance imaging (MRI) technique to quantify cerebral tissue volumes. Fourteen healthy term infants also were studied for comparison. A sequence of image processing algorithms was used to segment each of the MRI slices into the following separate tissue classes: cerebral cortical gray matter, basal ganglia/thalami, unmyelinated white matter, myelinated white matter, and cerebrospinal fluid, all classified based on magnetic resonance signal intensity and anatomic location. A final summing of voxels for each tissue class was performed to compute absolute volumes in milliliters. RESULTS: Cerebral cortical gray matter volume in premature infants treated with dexamethasone was reduced 35% when compared with gray matter volume in premature infants not treated with dexamethasone (mean +/- standard deviation, 130.3 +/- 54.0 vs 200.6 +/- 35.1 mL, respectively). Subcortical gray matter volumes (basal ganglia and thalami) and myelinated and unmyelinated white matter volumes were not significantly different among the treated and untreated groups. However, premature infants treated with dexamethasone exhibited a reduction (30%) in total cerebral tissue volume compared with total cerebral tissue volume in both the premature infants not treated with dexamethasone and the control term infants (312.7 +/- 43.7 vs 448.2 +/- 50.2 and 471.6 +/- 36.4 mL respectively). This latter finding relates primarily to the decrease in cerebral cortical gray matter volume. CONCLUSIONS: The data suggest an impairment in brain growth, principally affecting cerebral cortical gray matter, secondary to systemic dexamethasone therapy. Although the premature infants who received dexamethasone were smaller with more severe respiratory disease, these findings are consistent with growing evidence of a potential deleterious effect of dexamethasone on neonatal brain and subsequent neurodevelopmental outcome. This apparent deleterious effect should be taken into consideration by clinicians when weighing the potential risks and benefits of this therapy for low birth weight infants with neonatal chronic lung disease.

Case-Control Studies↗

Mortality among the residents of the Three Mile Island accident area: 1979-1992.

The largest U.S. population exposed to low-level radioactivity released by an accident at a nuclear power plant is composed of residents near the Three Mile Island (TMI) Plant on 28 March 1979. This paper (a collaboration of The University of Pittsburgh and the Pennsylvania Department of Health) reports on the mortality experience of the 32,135 members in this cohort for 1979-1992. We analyzed standardized mortality ratios (SMRs) using a local comparison population and performed relative risk regression modeling to assess overall mortality and specific cancer risks by confounding factors and radiation-related exposure variables. Total mortality was significantly elevated for both men and women (SMRs = 109 and 118, respectively). All heart disease accounted for 43.3% of total deaths and demonstrated elevated SMRs for heart disease of 113 and 130 for men and women, respectively; however, when controlling for confounders and natural background radiation, these elevations in heart disease were no longer evident. Overall cancer mortality was similar in this cohort as compared to the local population (male SMR = 100; female SMR = 101). In the relative risk modeling, there was a significant effect for all lymphatic and hematopoietic tissue in males in relation to natural background exposure (p = 0.04). However, no trend was noted. We found a significant linear trend for female breast cancer risk in relation to increasing levels of TMI-related likely [gamma]-exposure (p = 0.02). Although such a relationship has been noted in other investigations, emissions from the TMI incident were significantly lower than in other documented studies. Therefore, it is unlikely that this observed increase is related to radiation exposure on the day of the accident. The mortality surveillance of this cohort does not provide consistent evidence that radioactivity released during the TMI accident has a significant impact on the mortality experience of this cohort to date. However, continued follow-up of these individuals will provide a more comprehensive description of the morbidity and mortality experience of the cohort.

Adolescent↗

Measurement of non-linear microcrack accumulation rates in polymethylmethacrylate bone cement under cyclic loading.

Damage accumulation in the cement mantle used to fixate bone prosthesis is one failure scenario for joint reconstruction. It can be described as the phenomenon of numerous microcracks initiating and propagating within the material. Microcracks grow in the cement mantle causing it to gradually lose its mechanical integrity, leading to loosening of the prosthesis. In this study microcracking within acrylic bone cement was quantified over the course of a fatigue test. Identification of new cracks and the growth of pre-existing cracks was monitored at intervals during fatigue testing of five specimens at a mean cyclic stress of 7.5 MPa. Given these measurements, an average damage evolution curve was derived for acrylic bone cement. It was observed that the initiation sites for microcracks were the pore perimeters; therefore, the number of microcracks present in a sample is dependent on porosity. Variability was found within the results and the majority of the variability was accounted for by the difference in the porosity of each sample. Results have identified non-linear damage evolution. On a simplified level a power law equation can be used to describe the damage evolution process.

Journal Article↗

Electrophysiological measurements of spectral mechanisms in the retinas of two cervids: white-tailed deer (Odocoileus virginianus) and fallow deer (Dama dama).

Electroretinogram (ERG) flicker photometry was used to study the spectral mechanisms in the retinas of white-tailed deer (Odocoileus virginianus) and fallow deer (Dama dama). In addition to having a rod pigment with maximum sensitivity (lambda max) of about 497 nm, both species appear to have two classes of photopic receptors. They share in common a short-wavelength-sensitive cone mechanism having lambda max in the region of 450-460 nm. Each also has a cone having peak sensitivity in the middle wavelengths, but these differ slightly for the two species. In white-tailed deer the lambda max of this cone is about 537 nm; for the fallow deer the average lambda max value for this mechanism was 542 nm. Deer resemble other ungulates and many other types of mammal in having two classes of cone pigment and, thus, the requisite retinal basis for dichromatic color vision.

Animals↗