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Biomedical subjects

K Daly

Publications and source records attributed to K Daly.

At least 19 recordsLinked to original sources

Impact of flow path length and flow rate on phosphorus loss in simulated overland flow from a humic gleysol grassland soil.

In this overland flow simulation experiment, the relationships between flow path length, flow rate and the concentration of different P fractions were investigated. Overland flow was simulated using a 3 mx0.12 m laboratory flume. To remove the impact of rainfall on P lost in overland flow, simulated rainfall was not used during these experiments. Instead overland flow was generated by pumping water into the flume at the surface of the grass sod. The experimental setup allowed for the variation in flow path length and flow rate between and during experimental runs. The results demonstrated that an increase in flow path length caused an increase in Total Dissolved P (TDP), Dissolved Reactive P (DRP) and Total Reactive P (TRP) concentration in overland flow (p<0.01) while an increase in flow rate resulted in a decrease in the concentration of these P fractions in overland flow due to dilution (p<0.01). Total P (TP), Particulate P (PP) and Dissolved Organic P were not affected by the variables tested during this study. When flow path length was increased in conjunction with flow rate, there was an increase in TDP, DRP, and TRP concentrations despite the impact of greater dilution. The results indicate that variations in flow path length during a rainfall event may play a role in determining the concentration of dissolved P fractions in overland flow at field scale.

Phosphorus↗

Phosphorus retention and sorption by constructed wetland soils in Southeast Ireland.

It may be necessary to use constructed wetlands as a land use practice to mitigate phosphorus (P) loss from agriculture in Ireland. The objectives of this study were to determine the ability of two constructed wetland site soils to retain and sorb P. Intact soil/water column studies were used to determine P release/retention rates during a 30-day incubation period. Soil columns flooded with distilled water released P during the first 2 days; however, soluble reactive P (SRP) concentrations in overlying floodwaters decreased thereafter. Soils with overlying floodwaters spiked at 5 and 15 mg SRP L(-1) retained highest amounts of P (p < 0.05) with retention at these concentrations controlled by SRP in overlying waters. Retention rates by soils ranged between 0.3 and 60.9 mg Pm(-2) d(-1). Maximum P sorption capacity (Smax) was higher for wetland soils at Dunhill, Waterford (1464 mg P kg(-1)) in comparison to soils at Johnstown Castle, Wexford (618 mg P kg(-1)). Equilibrium P concentrations (EPC0) were low (in the microg SRP L(-1) range), indicating a high capacity of these soils to sorb P. Phosphorus sorption parameters were significantly related to ammonium oxalate extractable aluminium (Al) and iron (Fe) content of soils.

Adsorption↗

The importance of colonic butyrate transport to the regulation of genes associated with colonic tissue homoeostasis.

The transition from normality to malignancy in colorectal cancer is characterized by alterations in the expression of genes associated with the maintenance of tissue homoeostasis. Butyrate, a product of microbial fermentation of dietary fibre in the colon, is known to regulate a number of genes associated with the processes of proliferation, differentiation and apoptosis of colonic epithelial cells, and, hence, homoeostasis of colonic tissue. We have shown previously that the transport of butyrate into colonocytes is of fundamental importance to butyrate's regulatory ability, and therefore sought to assess the expression profile of butyrate-responsive genes in colon cancer tissue, where the expression of the colonic luminal-membrane butyrate transporter, MCT1 (monocarboxylate transporter 1), is significantly down-regulated. In the present paper, we first employed microarray analysis to assess global changes in butyrate-responsive genes using HT29 human colon carcinoma cells treated with butyrate. There was consistency in the butyrate response of selected genes in two other human colonic cell lines (HCT116 and AA/C1) using quantitative real-time PCR. Furthermore, we report that expression levels of selected butyrate-responsive genes involved in the processes of proliferation, differentiation and apoptosis, are deregulated in colon cancer tissue, correlating with decreased expression of MCT1. These findings support our hypothesis that a reduction in MCT1 expression, and hence butyrate transport, can lead to a reduction in the intracellular butyrate levels required to regulate gene expression. Collectively, our results highlight the important contribution of butyrate transport to the maintenance of tissue homoeostasis and disease prevention.

Biological Transport↗

Variant translocation with a deletion of derivative (9q) in a case of Philadelphia chromosome positive (Ph +) essential thrombocythemia (ET), a variant of chronic myelogenous leukemia (CML) with a poor prognosis.

Patients presenting with thrombocytosis require thorough clinical and laboratory evaluation to determine whether they suffer from essential thrombocythemia or another myeloproliferative disorder. This distinction becomes increasingly relevant as targeted agents become available to treat specific myeloproliferative diseases. Cytogenetic testing plays a major role in this analysis. This study presents a patient with Philadelphia chromosome positive (Ph + ) thrombocytosis and a cryptic der(9q)t(5;9)t(9;22) not found by conventional cytogenetics, whose disease progressed within 2 years to typical myeloblastic crisis of CML. It discusses the entity of Ph + ET, the utility of molecular cytogenetic testing in the diagnosis of this unusual disease entity and the importance of cytogenetic testing in the prognosis of ET.

Aged↗

Current status of catheter- and stent-based gene therapy.

Significant progress has been made in the field of cardiovascular gene therapy over the past decade. Animal models of human disease have helped in identifying potential therapeutic genes and have also assisted in the evaluation of an ideal vector. A number of percutaneous catheter systems have been used in animal models with limited success. Stents represent an attractive alternative for localized gene delivery, as they provide a platform for prolonged gene elution and efficient transduction of opposed arterial walls. This gene delivery strategy has the potential to decrease the systemic spread of the viral vectors and hence a reduced host immune response. Both synthetic and naturally occurring stent coatings have shown potential to allow prolonged gene elution with no significant adverse reaction. However, further animal studies are required to evaluate the compatibility of stent coatings, vector solutions, and the arterial wall as well as assessment of the feasibility of this approach to achieve the full potential of gene therapy.

Animals↗

Paradoxical cerebral embolisation. An explanation for fat embolism syndrome.

Fat embolism occurs following fractures of a long bone or arthroplasty. We investigated whether paradoxical embolisation through a venous-to-arterial circulation shunt (v-a) could lead to cerebral embolisation during elective hip or knee arthroplasty. Transcranial Doppler ultrasound (TCD), following the intravenous injection of microbubble contrast, identified the presence of a shunt in 41 patients undergoing hip (n = 20) or knee (n = 21) arthroplasty. Intra-operative cerebral embolism was detected during continuous TCD monitoring. Of the 41 patients, 34 had a v-a shunt of whom 18 had an embolism and embolism only occurred in patients with a shunt (p = 0.012). Spontaneous and larger shunts were associated with a greater number of emboli (rs = 0.67 and rs = 0.71 respectively, p < 0.01). Observations in two patients with large spontaneous shunts revealed 368 and 203 emboli and unexplained post-operative confusion and pancreatitis. Paradoxical cerebral embolisation only occurred in patients with a shunt and may explain both postoperative confusion and fat embolism syndrome following surgery.

Adult↗

Current management of torus fractures of the distal radius.

The use of a forearm cast for paediatric buckle fractures of the distal radius is widespread practice. These fractures do not displace and follow-up in fracture clinic is only for cast removal. This may mean missed school for the child, or work for parents. Modern materials allow a robust lightweight backslab to be used for protection of these stable, though painful, injuries. Unlike a plaster of Paris backslab, Prelude (Smith and Nephew) is removed by unwrapping the outer bandage. Parents can do this at home. We prospectively studied 41 consecutive children aged 12 years or less with buckle fractures of the distal radius, presenting to our fracture clinic. After the diagnosis of isolated buckle fracture was confirmed, a Prelude backslab was applied. Parents were given a full explanation and written instructions, which were also sent to the GP. Telephone follow-up was carried out at 3-4 weeks. Forty out of forty-one parents expressed satisfaction with both the treatment and the instructions. The parents of one patient misunderstood the instructions, represented to fracture clinic and were dissatisfied for this reason.With modern casting materials and adequate instructions in fracture clinic, further follow-up of patients with buckle fractures is unnecessary. Resource savings can be made in this way with no compromise to patient care and increased patient/parent satisfaction.

Aftercare↗

Reduction in mortality after inappropriate early discharge from intensive care unit: logistic regression triage model.

OBJECTIVE: To develop a predictive model to triage patients for discharge from intensive care units to reduce mortality after discharge. DESIGN: Logistic regression analyses and modelling of data from patients who were discharged from intensive care units. SETTING: Guy's hospital intensive care unit and 19 other UK intensive care units from 1989 to 1998. PARTICIPANTS: 5475 patients for the development of the model and 8449 for validation. MAIN OUTCOME MEASURES: Mortality after discharge and power of triage model. RESULTS: Mortality after discharge from intensive care was up to 12.4%. The triage model identified patients at risk from death on the ward with a sensitivity of 65.5% and specificity of 87.6%, and an area under the receiver operating curve of 0.86. Variables in the model were age, end stage disease, length of stay in unit, cardiothoracic surgery, and physiology. In the validation dataset the 34% of the patients identified as at risk had a discharge mortality of 25% compared with a 4% mortality among those not at risk. CONCLUSIONS: The discharge mortality of at risk patients may be reduced by 39% if they remain in intensive care units for another 48 hours. The discharge triage model to identify patients at risk from too early and inappropriate discharge from intensive care may help doctors to make the difficult clinical decision of whom to discharge to make room for a patient requiring urgent admission to the unit. If confirmed, this study has implications on the provision of resources.

APACHE↗

Isolation and characterization of a novel hydrocarbon-degrading, Gram-positive bacterium, isolated from intertidal beach sediment, and description of Planococcus alkanoclasticus sp. nov.

AIMS: Characterization of a bacterial isolate (strain MAE2) from intertidal beach sediment capable of degrading linear and branched alkanes. METHODS AND RESULTS: A Gram-positive, aerobic, heterotrophic bacterium (strain MAE2), that was capable of extensive degradation of alkanes in crude oil but had a limited capacity for the utilization of other organic compounds, was isolated from intertidal beach sediment. MAE2 had an obligate requirement for NaCl but could not tolerate high salt concentrations. It was capable of degrading branched and n-alkanes in crude oil from C11 to C33, but was unable to degrade aromatic hydrocarbons. Comparative 16S rRNA sequence analysis placed the isolate with members of the genus Planococcus. That finding was corroborated by chemotaxonomic and physiological data. The fatty acid composition of strain MAE2 was very similar to the type species of the genus Planococcus, P. citreus (NCIMB 1493T) and P. kocurii (NCIMB 629T), and was dominated by branched acids, mainly a15:0. However, the 16S rRNA of strain MAE2 had less than 97% sequence identity with the type strains of P. citreus (NCIMB 1439T), P. kocurii (NCIMB 629T) and two Planococcus spp. (strain MB6-16 and strain ICO24) isolated from Antarctic sea ice. This indicated that strain MAE2 represented a separate species from these planococci. Morphologically, the isolate resembled P. okeanokoites (NCIMB 561T) and P. mcmeekinii S23F2 (ATCC 700539T). The cellular fatty acid composition of P. okeanokoites and P. mcmeekinii was considerably different from strain MAE2, and the mol % G + C content of P. mcmeekinii was far lower than that of MAE2. CONCLUSION: On the basis of phenotypic and genotypic data, it is proposed that strain MAE2 is a new species of Planococcus, Planococcus alkanoclasticus sp. nov., for which the type strain is P. alkanoclasticus MAE2 (NCIMB 13489T). SIGNIFICANCE AND IMPACT OF THE STUDY: Planococcus species are abundant members of the bacterial community in a variety of marine environments, including some in sensitive Antarctic ecosystems. The occurrence of hydrocarbon-degrading Planococcus spp. is potentially of importance in controlling the impact of hydrocarbon contamination in sensitive marine environments.

Alkanes↗

Typical Friedreich's ataxia without GAA expansions and GAA expansion without typical Friedreich's ataxia.

We clinically assessed and performed polymerase chain reaction analysis for the GAA trinucleotide repeat expansion in 103 patients from 73 families in Ireland, with a prior clinical diagnosis of Friedreich's ataxia (FA) or an unclassified progressive ataxic syndrome. The patients were classified as "typical" or "atypical" FA according to Harding's mandatory clinical diagnostic criteria. All patients underwent blood glucose analysis, and electrocardiography and echocardiography was performed in 99 and 101 patients, respectively. Mutation screening for expanded CAG trinucleotide repeats, associated with spinocerebellar ataxia (SCA) 1, 2, 3 and 6 was performed in 86 patients overall, including all GAA negative patients. Forty-nine of 56 typical patients and 13 of 47 atypical patients were either homozygous or heterozygous for the GAA expansion. Seven patients with a typical FA phenotype were negative for the GAA expansion. Although one of these patients had vitamin E deficiency, and two had raised alpha-fetoprotein levels, three other GAA negative patients with a typical FA phenotype had no other identifiable cause for their ataxia, once again raising the possibility of locus heterogeneity in FA. It is also possible that these patients have two point mutations in the X25 gene, or that they have another ataxic syndrome mimicking the FA phenotype. Two families who were homozygous for the GAA expansion exhibited intrafamilial phenotypic variability. Only one GAA negative patient had the SCA 3 mutation, and this was the only patient in the study with a possible autosomal dominant inheritance pattern. In the homozygous GAA population typical patients had significantly more repeats on the smaller allele than atypical patients, and there was an inverse relationship between the number of repeats on the smaller allele and the age at presentation. There was also an inverse relationship between the repeat size on both the larger and the smaller of the two alleles and the age at becoming wheelchair bound. There was no significant relationship between repeat size and the other indices of disease severity, including the presence or absence of diabetes or cardiomyopathy. This is the first large study of an Irish population with progressive ataxia that has shown a similar phenotype/genotype relationship to studies of FA in other European and non-European populations. The relatively low sensitivity and specificity of Harding's clinical diagnostic criteria must be appreciated when clinically assessing patients with a progressive ataxic syndrome. Although molecular genetic analysis now plays an essential role in diagnosis and classification, patients with a typical FA phenotype without any identifiable cause for their ataxia exist.

Adolescent↗

Cardiac troponin I in pre-eclampsia and gestational hypertension.

OBJECTIVE: To investigate serum cardiac troponin I, a sensitive marker of cardiac myocyte damage, in normal pregnancy and pregnancies complicated by hypertension with and without significant proteinuria. DESIGN: Prospective cross sectional study. SETTING: University hospital delivery suite. SAMPLE: Serum samples obtained from women in normal pregnancy and in pregnancies complicated by hypertension with and without significant proteinuria. METHOD: Women with hypertension in pregnancy (at least two readings of systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg) (n = 26) and normotensive women (n = 43) were included in the study. Serum cardiac troponin I was measured using Beckman Access immunoassay. MAIN OUTCOME MEASURE: Serum cardiac troponin I level in the pregnancies complicated by hypertension (with and without significant proteinuria) compared with the levels measured in normotensive women. RESULTS: The median serum cardiac troponin I level in pregnancies complicated by hypertension was 0.118 ng/mL (n = 26) which was significantly greater than that measured in samples obtained from normotensive women in pregnancy (0.03 ng/mL; n = 43) (P < 0.0001). There were higher median serum cardiac troponin I levels in hypertensive women with significant proteinuria (0.155 ng/mL; n = 6), compared with those without proteinuria (0.089 ng/mL; n = 20; P = 0.03). CONCLUSION: Serum cardiac troponin I is elevated in women with hypertensive disorders of pregnancy indicating some degree of cardiac myofibrillary damage in these disorders.

Adult↗

Outcome measures for adult critical care: a systematic review.

OBJECTIVES: 1. To identify generic and disease specific measures of impairment, functional status and health-related quality of life that have been used in adult critical care (intensive and high-dependency care) survivors. 2. To review the validity, reliability and responsiveness of the measures in adult critical care survivors. 3. To consider the implications for future policy and to make recommendations for further methodological research. 4. To review what is currently known of the outcome of adult critical care. METHODS DATA SOURCES: Searches of electronic databases (MEDLINE, EMBASE, CINAHL, PsycLIT, The Cochrane Library and SIGLE) from 1970 to August 1998. Manual searches of five journals (1985-98) not indexed in electronic databases and relevant conference proceedings (1993-98). Reference lists of six existing reviews, plus snowballing from reference lists of all relevant articles identified. STUDY SELECTION: Randomised trials, non-randomised trials (cohort studies) and case series that included data on outcomes after discharge from adult (16 years and over) critical care. DATA EXTRACTION AND SYNTHESIS: If reported, the following data were extracted from each paper: patient characteristics (age, gender, severity of illness, diagnostic category) number of patients eligible for study, follow-up period, number of deaths before follow-up, number and proportion of survivors included in follow-up method of presentation of outcome data - proportion normal as defined by reference values, or aggregate value (e.g. mean or median), or aggregate values plus an indication of variance (e.g. standard deviation or inter-quartile range). Evidence for three measurement properties was sought for each outcome measure that had been used in at least two studies - their validity, reliability and responsiveness in adult critical care. If the authors did not report these aspects explicitly, an attempt was made to use the data provided to provide these measurement properties. For measures that were used in at least ten studies, information on actual reported outcomes were also extracted. RESULTS: MEASURES USED IN CRITICAL CARE: Measures of impairment were largely confined to the respiratory system so are almost certainly not appropriate for many critical care survivors. They can be categorised as respiratory volumes (e.g. vital capacity), gas flow within the respiratory system (e.g. forced expiratory volume in 1 second (FEV1)), pulmonary diffusing capacity (e.g. carbon monoxide diffusing capacity) and visualisation of the upper airway (e.g. bronchoscopy). Multiple tests are often performed. Eight measures of physical functional status were used, five generic and three disease-specific. The most frequently used generic measures were multi-item scales. Two single-item global measures attempted to capture a person's overall activity level or functional status. Five multi-item measures of mental functional status were used, four generic and one specific to trauma patients. The generic measures were either confined to assessing depressive symptoms or also encompassed a measure of anxiety. Measures of neuropsychological functioning relate to a person's cognition, attention, ability to process information and memory. Apart from one single-item measure, which focused on communication level, six multi-item measures were used with critical care survivors. Such measures are particularly appropriate for use with survivors of head injury or other neurological insult and, in that sense, they are disease-specific rather than generic measures. Single item measures of recovery were frequently used but researchers often invented their own, so there was little consistency in the wording. These measures had five principal foci - return to work, return to own home, degree of recovery, productivity and chronic health status. One multi-item scale was also used. (ABSTRACT TRUNCATED)

Adult↗

Altered helper T lymphocyte function associated with chronic hepatitis B virus infection and its role in response to therapeutic vaccination in humans.

Theradigm-hepatitis B virus (HBV) is an experimental lipopeptide vaccine designed to stimulate induction of HBV-specific CTL responses in HLA-A2 individuals. Previous studies had demonstrated high immunogenicity in healthy volunteers, but comparatively weak CTL responses in chronically infected HBV patients. Herein, we examined helper T lymphocyte (HTL) responses in chronically infected patients. Despite normal proliferation and IL-2 secretion, IL-12 and IFN-gamma secretion in vitro in response to the vaccine was reduced compared with healthy volunteers. A similar pattern of cytokine secretion was observed following mitogen stimulation, suggesting a general altered balance of Th1/Th2 responses. Further analysis indicated that HTL recall responses to whole tetanus toxoid protein were reduced in chronically infected subjects, and reduced responsiveness correlated with the outcome of Theradigm-HBV immunization. Finally, experiments in HBV transgenic mice indicated that the nonnatural Pan DR HTL epitope, PADRE, is capable of inducing high levels of IFN-gamma secretion and that its inclusion in a lipopeptide incorporating an immunodominant Ld-restricted CTL epitope resulted in breaking tolerance at the CTL level. Overall, our results demonstrate an alteration in the quality of HTL responses induced in chronically infected HBV patients and suggest that use of a potent HTL epitope may be important to overcome CTL tolerance against specific HBV Ags.

Animals↗

Prospective study of tympanic membrane retraction, hearing loss, and multifrequency tympanometry.

Tympanic membrane retraction is a significant sequela of OME and has been linked clinically to atelectasis, ossicular erosion, and cholesteatoma. We investigated important factors for prediction of tympanic membrane retraction in a prospective study of 112 children. After 4 to 6 years of follow-up, 12% of ears had pars tensa retraction without atrophy, and 28% had various degrees of retraction with atrophy. Mild pars flaccida retraction was present in 23%, and severe pars flaccida retraction was present in 12%. Retraction severity was related to hearing level and multifrequency tympanometry. Three factors were significantly related to retraction severity: type of tube, male sex, and percent of visits in the second year with abnormal tympanograms. This study shows that type of tube was the most important factor in long-term outcome after tympanostomy tube treatment of OME.

Acoustic Impedance Tests↗

Lateral shelf acetabuloplasty in Perthes' disease. A review of the end of growth.

The surgical treatment of Perthes' disease by femoral or innominate osteotomy is not as effective in those over the age of eight years as it is in the younger child. This has prompted the search for other types of management in those who are older. The preliminary results of the use of a lateral shelf acetabuloplasty for such cases have shown encouraging results at two years. The concern with such an operation is that it might interfere with the growth of the outer aspect of the acetabulum and so prejudice the long-term outcome. We describe a review at maturity of 26 children presenting with early disease after the age of eight years who were treated by lateral shelf acetabuloplasty. The results suggest that the outcome is improved; 22 of 27 hips were rated as Stulberg groups 1 to 3. Poor results occurred in children, particularly girls, presenting with Group-4 disease over the age of 11 years.

Acetabulum↗