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Biomedical subjects

K M Taylor

Publications and source records attributed to K M Taylor.

At least 109 records · Page 6Linked to original sources
PubMed1998

Localised cerebral phosphorus-31 MR spectroscopy in man before and immediately after coronary bypass surgery with hypothermic cardiopulmonary bypass.

Coronary artery bypass surgery classically is undertaken with hypothermic cardiopulmonary bypass (CPB). There is a high incidence of neuropsychological defects after cardiac surgery, which may be related to cerebral ischaemia during the rewarming period. In this study, phosphorus-31 magnetic resonance spectroscopy (31P MRS) was used to identify changes in cerebral 31P MR spectra in patients before and immediately after hypothermic CPB. Four neurologically normal patients undergoing coronary artery bypass surgery were studied. Localised cerebral 31P MRS (TR 5000 ms) was performed at 1.5 Tesla on each patient the day before and within an hour of completion of surgery. Peak areas for phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr) and beta ATP (betaATP) were measured. Metabolite peak area ratios and relative percentages of each 31P MR resonance with respect to the total 31P MR signal were calculated. In the post-operative MR spectra, each patient displayed a marked reduction in Pi/betaATP and increase in PCr/Pi ratios. Spectral changes in percentage metabolite signals following surgery varied both in magnitude and pattern between patients. In two patients there was an increased postoperative percentage PME and percentage PCr with a decrease in percentage betaATP. The converse was found in the other two patients, but all four subjects displayed a markedly decreased percentage Pi after CPB. These metabolite changes probably reflect rebound phosphorylation in the immediate postoperative period and suggest increased metabolic activity in the hyperaemic brain on rewarming from hypothermic CPB.

Aged↗
PubMed1998

Imaging bioluminescent indicators shows Ca2+ and ATP permeability thresholds in live cells attacked by complement.

A series of permeability thresholds to Ca2+ metabolites and macromolecules, occurring at different times when cells are attacked by complement, has been established by imaging HeLa cells transiently expressing a recombinant cytosolic fusion protein of firefly luciferase and aequorin (luciferase-aequorin) to measure changes in ATP and cytosolic free Ca2+. Nuclear fluorescence of propidium was used as a measure of permeability to small molecules, and luciferase activity imaged to assess lysis. The rise in cytosolic free Ca2+ observed after C9 attack preceded by at least 60 s both the increase in propidium fluorescence, measured in single cells, and the decrease in ATP monitored by luciferase light emission. These effects were dependent on the concentration of C9. At concentrations of C9 up to 4 micrograms/ml no loss of luciferase-aequorin protein was detected at the end of the experiment. Thus the membrane integrity of the cells remained intact, even though the cells were permeable to propidium. These results confirmed our earlier observations that propidium permeability in cells attacked by complement was not a reliable measure of cell death. They also show that it is vital to take account of cellular heterogeneity if the mechanisms by which cells respond to membrane pore former attack are to be correctly interpreted.

Adenosine Triphosphate↗
PubMed1998

Cerebral swelling after normothermic cardiopulmonary bypass.

BACKGROUND: Marked cerebral swelling visible on magnetic resonance images has been found immediately after hypothermic (28 degrees C) cardiopulmonary bypass. The mechanism is unknown, but indices of cerebral ischemia are seen during rewarming from hypothermic bypass that are not present with normothermic bypass (37 degrees C). METHODS: T1-weighted and fluid-attenuated inversion recovery magnetic resonance images were taken of seven patients undergoing routine coronary artery bypass surgery before, 1 h, and 7 days after the operation using normothermic bypass. RESULTS: Marked cerebral swelling was seen in fluid-attenuated inversion recovery images in five of seven patients 1 h after bypass. Scans in four patients taken 7 days after bypass showed that the cerebral swelling had returned to normal. There was no change in cerebral ventricular size, and all patients had uncomplicated postoperative courses. CONCLUSIONS: Normothermic bypass is followed by acute postoperative cerebral swelling. However, the amount of swelling was similar to that found in a previous study after hypothermic bypass. The mechanism of swelling is still obscure, and its relation to neurologic outcome is unknown.

Aged↗
PubMed1998

Magnetic resonance spectroscopy of high-energy phosphates and lactate immediately after coronary artery bypass surgery.

Hypothermic cardiopulmonary bypass (CPB) is associated with a high incidence of neuropsychological defects, marked cerebral swelling immediately after surgery and jugular bulb desaturation during rewarming. This suggests cerebral ischaemia may occur, but evidence is indirect. We studied four patients with 31P magnetic resonance spectroscopy (MRS) and four with 1H MRS before and immediately after coronary surgery. There was no visible lactate in 1H MR spectra. In 31P MR spectra, the ratio of phosphocreatine to adenosine triphosphate was maintained (before: 2.13 +/- 0.86 vs after: 2.57 +/- 1.31; mean +/- 1 SD) and there was no intracellular acidosis (intracellular pH: 7.1 +/- 0.04 vs 7.16 +/- 0.08), while phosphocreatine/inorganic phosphate was increased immediately after the operation (2.92 +/- 0.37 vs 6.39 +/- 2.67, p = 0.03). This suggests rebound replacement of energy stores following recovery from temporary cerebral ischaemia during CPB: intra-operative studies would be needed to test this hypothesis further.

Brain Ischemia↗
PubMed1998

Quality-of-life information and clinical practice: the oncologist's perspective.

OBJECTIVE: To collect information from a group of Canadian oncologists about their perspectives on quality of life (QOL) and QOL information. DESIGN: A self-administered questionnaire (MD-QOL) containing 75 items with a 4-point Likert categorical response scale was administered by mail using Dillman survey methodology to all staff oncologists at a single institution. SETTING: A large Canadian cancer care centre (Princess Margaret Hospital, Toronto). MAIN OUTCOME MEASURES: Oncologists' knowledge, attitude, current behaviour and intended willingness to use QOL information. RESULTS: Of 67 eligible respondents 54 replied (80% response rate). In all, 74% felt that QOL can be quantified, and 95% felt that it gives information distinct from performance status measures. A total of 87% felt that published QOL data are useful for individual patient care, but 69% indicated that, at present, they would be more likely to base their recommendations on personal experience rather than on published literature. Of the respondents, 57% felt that decisions were made more difficult when QOL issues are considered. CONCLUSIONS: The surveyed oncologists support the relevance and importance of QOL information. Data from this study were used to develop a predictive model to assess oncologists' willingness to use QOL information; the model is being tested in other studies.

Adult↗
PubMed1997

Aortic valve replacement in patients 80 years of age and older: survival and cause of death based on 1100 cases: collective results from the UK Heart Valve Registry.

BACKGROUND: Aging of the population and advances in preoperative and postoperative care are reflected in an increasing number of patients > or = 80 years of age undergoing aortic valve replacement (AVR) in the United Kingdom. The present study presents data on postoperative 30-day mortality, actuarial survival, and cause of death based on a large collective patient population. METHODS AND RESULTS: Data were extracted from the UK Heart Valve Registry. From January 1986 to December 1995, 1100 patients > or = 80 years of age underwent AVR and were reported to the registry. Six hundred eleven patients (55.5%) were women. The mean follow-up time was 38.9 months. The 30-day mortality was 6.6%. Of the 73 early deaths, 42 were due to cardiac reasons. The actuarial survival was 89%, 79.3%, 68.7%, and 45.8% at 1, 3, 5, and 8 years, respectively. After the first 30 postoperative days, 144 of the 205 deaths were due to noncardiac reasons. Malignancy, stroke, and pneumonia were the most common causes of late death. Bioprosthetic valves were implanted in 969 patients (88%) and mechanical valves in 131 (12%) patients. There was no difference in early mortality and actuarial survival between the two groups (P>.05). CONCLUSIONS: The above results suggest that under the selection criteria for AVR currently applied in the United Kingdom, patients > or = 80 years of age show a satisfactory early postoperative outcome and moderate medium-term survival benefit.

Aged↗
PubMed1997

Optimizing a limiting dilution culture system for quantifying the frequency of interleukin-2-producing alloreactive T helper lymphocytes.

BACKGROUND: The development of sensitive, specific, and reproducible techniques to quantify T cells with direct allospecificity has potential applications in the selection of bone marrow donors and in the monitoring of the antidonor alloresponse in patients after organ transplantation. Such data may provide an objective basis for altering existing immunosuppression, monitoring novel antirejection therapies, and predicting long-term graft outcome. We have previously published a correlation between donor antirecipient T helper frequencies (HTLf) and the severity of acute graft-versus-host disease after bone marrow transplantation. Using the same assay protocol, we have described the development of donor-specific hyporesponsiveness in a proportion of renal transplant recipients. However, several imperfections existed in the protocols used in these studies. Cellular interactions within the stimulator and the responder cell populations, and back stimulation of T cells within the stimulator cell population, could give rise to extraneous interleukin-2 and alter the validity or estimation of derived recipient antidonor HTLf. METHODS: Using peripheral blood mononuclear cells as the responding population and splenic mononuclear cells as the stimulating population, we have examined the possible effects of these cellular interactions on the results of limiting dilution analysis assays for HTLf measurement. RESULTS: These interactions have the ability to alter the validity or estimation of HTLf. We show that by depleting the responder population of HLA class II+ cells and depleting T cells from the stimulating population, these interactions are effectively abrogated. CONCLUSIONS: On the basis of the findings reported here, we describe an optimized HTLf assay which is sensitive, specific, and reproducible. This has obvious applications in the analysis of alloimmune responses in transplantation.

Bone Marrow Transplantation↗
PubMed1997

Effect of cardiopulmonary bypass perfusion protocols on gut tissue oxygenation and blood flow.

BACKGROUND: Previous studies in patients undergoing cardiopulmonary bypass (CPB) have documented gastric mucosal hypoperfusion and hypoxia. This study examines the influence of the CPB protocol on the adequacy of gut blood flow and oxygenation. METHODS: Twenty-four patients were prospectively randomized into one of four CPB groups: nonpulsatile hypothermic (NP 28); pulsatile hypothermic (P 28); non-pulsatile normothermic (NP 37); and pulsatile normothermic (P 37). Gastric wall blood flow was assessed using laser Doppler flow measurement and gastric mucosal oxygenation (intramucosal pH), using tonometry. RESULTS: After 10 minutes of CPB, the NP 28 group had the greatest reduction in gastric wall blood flow (-60.6% +/- 3.8%) compared with baseline (p < 0.05). Thirty minutes into CPB, the P 37 group had less gastric mucosal hypoperfusion (-9.7% +/- 10.3%) than the NP 28 patients (-53.0% +/- 8.6%; p < 0.05). All groups showed a hyperemic response immediately after CPB. No significant differences between the four groups were found for gastric mucosal oxygenation during or after CPB. A progressive decline occurred in this variable during the period 3 to 4 hours after CPB. At this time, total-body oxygen consumption and extraction were at their maximum. CONCLUSIONS: This study found that perfusion protocol can influence mucosal blood flow, but other overriding factors that operate during and after CPB act to cause mucosal hypoxia. These findings, particularly the timing of mucosal hypoxia, may have implications for centers contemplating early extubation or "fast tracking" of patients after CPB.

Adult↗
PubMed1997

EEG changes during cardiopulmonary bypass surgery and postoperative neuropsychological deficit: the effect of bubble and membrane oxygenators.

OBJECTIVE: Quantitative electroencephalography was used during cardiopulmonary bypass surgery to determine the point in time of most neuronal functional change which may result in postoperative neuropsychological deficit. It was also used to determine any relationship between quantitative electroencephalography changes and type of oxygenator used in surgery. METHODS: We studied 61 coronary artery bypass graft patients. Anaesthesia included thiopental, fentanyl and N2O. Surgery was performed with hypothermic bypass (28 degrees C), arterial pressure of 50-70 mmHg, and alpha-stat, using bubble (Harvey 1700), or membrane (Cobe CML) oxygenators, both with arterial line filters (Pall 40 microns). RESULTS: The main finding was a significant increase in delta power at the end of perfusion (P < 0.01), which showed a positive association with delta power before the start of perfusion. Marked quantitative electroencephalography change at the end of perfusion was not related to systemic hypotension, temperature, type of oxygenator, bypass time, or patient age. Intraoperative quantitative electroencephalography changes found in most patients were transient and could not be related to postoperative cerebral function. However, 16 of the 18 patients who had neuropsychological deficit 2 months after surgery, also had a significant quantitative electroencephalography change at the end of perfusion. CONCLUSIONS: While no difference in anaesthetic technique was found between patients, the variation in quantitative electroencephalography power before perfusion may indicate a difference in individual response to anaesthetic. Usefulness of quantitative electroencephalography to predict postoperative cerebral functional deficit remains doubtful.

Aged↗
PubMed1997

Survival and cause of death after mitral valve replacement in patients aged 80 years and over: collective results from the UK heart valve registry.

OBJECTIVE: Over the last decade there has been an increasing number of patients aged 80 years and over undergoing heart valve replacement. However, literature on the outcome of mitral valve replacement (MVR) in this age group is still limited. METHODS: We conducted the present study by analysing data extracted from the UK Heart Valve Registry. From January 1986 to December 1994, 86 patients underwent isolated MVR and 10 underwent combined MVR with aortic valve replacement (AVR) and were reported to the Registry. RESULTS: The 30 day mortality was 10.4% (9/86) in the MVR group and 10% (1/10) in the MVR and AVR group. The actuarial survival was 79.8, 64.1 and 40.7% at 1, 3 and 5 years, respectively, in the MVR group. Of the 10 early (30 day) deaths, 8 were due to cardiac reasons and 19 of the 28 late deaths were due to non-cardiac reasons. A total of 55 (57.2%) patients received a bioprosthetic valve implant and 41 (42.8%) patients received a mechanical valve implant. There was no difference in survival between the two groups. CONCLUSIONS: The above results suggest that MVR in octogenarians produces a satisfactory early postoperative outcome and moderate medium-term benefit. There is no difference in survival between patients receiving bioprosthetic and patients receiving mechanical valve implants.

Actuarial Analysis↗
PubMed1997

Mutation of recombinant complement component C9 reveals the significance of the N-terminal region for polymerization.

Complement component C9 binds to C5b-8 sites on target cells and polymerizes to form the membrane attack complex (MAC). The aim of the work reported here was to discover which region within C9 was responsible for protecting the globular protein against self-polymerization. Computer prediction modelling highlighted the domain at the N-terminus of C9, which was then investigated by site-directed mutagenesis. The mutated proteins were expressed using insect cells infected with baculovirus. Removal of 16, 20 or 23 amino acids at the N-terminus of C9 resulted in inactivation due to self-polymerization. In contrast, removal of 4, 8 or 12 amino acids resulted in a C9 that did not polymerize spontaneously, had two to threefold enhanced lytic activity on erythrocytes, and had increased binding to C5b-8 sites on rat neutrophils. These results suggest that the domain within the first 16 amino acids at the N-terminus of C9 is crucial in preventing the self-polymerization of the globular protein. We have also found that C9 contains a motif (27WSEWS31) common to a family of cytokine receptors that is similar to a tryptophan-rich motif (WEWWR) of the membrane pore formers, thiol-activated cytolysins. Mutation of this motif in C9 resulted in polymerized protein, consistent with this site keeping the N-terminus in a protected conformation and preventing premature self-polymerization.

Amino Acid Sequence↗
PubMed1997

Rational approach to combined carotid and ischaemic heart disease.

BACKGROUND: The management of patients with concomitant coronary and carotid artery disease remains a controversial subject. The aim of this review was to develop a rational plan for the management of such patients based on a review of the literature. METHOD AND RESULTS: A retrospective review was carried out of relevant papers derived from the Medline database from 1964 to 1996. CONCLUSION: The management of patients with concomitant coronary and carotid artery disease has not yet been put to the test in a properly designed and randomized multicentre trial. It is suggested that, until the results of such a trial are available, the rational approach to combined symptomatic disease is combined carotid endarterectomy and coronary artery bypass grafting (CABG). Combined surgery is also appropriate for patients with symptomatic carotid artery disease and significant but asymptomatic cardiac disease. At present there is inadequate evidence to promote carotid endarterectomy for asymptomatic disease in combination with CABG.

Carotid Artery Diseases↗
PubMed1996

Localization and targeting of isocitrate lyases in Saccharomyces cerevisiae.

Native isocitrate lyase from castor bean and a C-terminally truncated variant were expressed in Saccharomyces cerevisiae under the control of a galactose-inducible promoter. Both forms of isocitrate lyase were targeted to the yeast peroxisomes. They co-fractionated with catalase on sucrose-density-gradient centrifugation of a post-nuclear supernatant prepared from cells grown on oleic acid plus galactose, but were found in the cytosolic fractions when the cells were grown under conditions that repress peroxisome formation. The endogenous S. cerevisiae isocitrate lyase was found solely in the cytoplasmic fractions, even under growth conditions that induce peroxisome proliferation. This result shows that the presence of isocitrate lyase in peroxisomes is not essential for a functional glyoxylate cycle. Although the heterologous enzyme was transported to peroxisomes it was not enzymically active. Immunocytochemical studies provide independent evidence that the plant enzyme is imported into the matrix of yeast peroxisomes.

Amino Acid Sequence↗
PubMed1996

Inhibition of proliferation and induction of apoptosis in juvenile myelomonocytic leukemic cells by the granulocyte-macrophage colony-stimulating factor analogue E21R.

Juvenile myelomonocytic leukemia (JMML) is a malignancy that almost inevitably leads to death before adulthood. Chemotherapy has given disappointing results and a substantial number of patients relapse after bone marrow transplantation. A salient feature of this disease is that the JMML cells produce granulocyte-macrophage colony-stimulating factor (GM-CSF) spontaneously and survive and proliferate without exogeneous GM-CSF. Furthermore, JMML cells are hypersensitive to GM-CSF with addition of this cytokine leading to enhanced proliferation. We have recently generated a human GM-CSF analogue, E21R, that acts as a complete and selective GM-CSF receptor antagonist. We have now tested this molecule as a potential new agent to control the leukemic cell load in JMML with particular emphasis on its role in JMML cell survival. We found that E21R inhibited the spontaneous growth of JMML cells in vitro and caused their apoptosis in a dose- and time-dependent manner in seven of seven cases. In contrast, neither a neutralizing anti-GM-CSF monoclonal antibody (MoAb) nor a selective interleukin-1 (IL-1) receptor antagonist affected JMML cell survival. Furthermore, the apoptotic effect of E21R was seen even in the presence of interleukin-1 beta and tumor necrosis factor-alpha, which have also been implicated in the pathogenesis of JMML. The inhibitory effects of E21R on JMML cell growth and viability offer a novel approach to therapy in this lethal childhood leukemia.

Antibodies, Monoclonal↗