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Biomedical subjects

C Snowden

Publications and source records attributed to C Snowden.

12 recordsLinked to original sources
PubMed2006

Relationship between perioperative troponin elevation and other indicators of myocardial injury in vascular surgery patients.

BACKGROUND: In 2000 the European Society of Cardiology and the American College of Cardiology published a consensus document revising the definition of myocardial infarction. The usefulness of this revised definition has been challenged. It has been suggested that, rather than any release of cardiac troponin being potentially diagnostic of myocardial infarction, a diagnostic threshold consistent with significant myocardial injury should be defined. METHODS: We studied 65 patients undergoing elective major vascular surgery to examine the relationship between the magnitude of cardiac troponin I (cTnI) and creatine kinase MB fraction (CK-MB) release and clinical signs or symptoms of myocardial injury. cTnI and CK-MB concentrations were measured preoperatively and on the first 4 postoperative days using the ACCESS assay (Beckmann). Patients were considered to have suffered a perioperative myocardial infarction if they had either symptoms or ECG changes consistent with this diagnosis, together with cTnI release. RESULTS: Peak postoperative cTnI concentrations above the lower detection limit of the ACCESS assay (0.06 microg litre(-1)) occurred in 26 patients. Eight of these patients displayed symptoms or ECG changes consistent with myocardial injury. A cTnI level greater than 0.68 microg litre(-1) was found to be consistent with the clinical diagnosis of myocardial infarction. The optimal cut-off for the diagnosis of MI using CK-MB was 40.4 microg litre(-1). CONCLUSIONS: These data suggest that further studies are required to define the optimal cardiac troponin diagnostic threshold for the diagnosis of myocardial infarction in the non-cardiac surgery population.

Aged↗
PubMed2001

Machine perfusion for kidneys: how to do it at minimal cost.

Due to a shortage of organs for transplantation, many centres use marginal grafts to increase their donor pool. As kidneys from non-heart-beating donors (NHBD) have sustained initial ischaemic damage, their viability is difficult to predict. Hypothermic pulsatile perfusion has not only been used to improve the condition of such grafts, but also allows viability assessment. Suitable systems are becoming more readily available, but they are expensive. We have used existing dialysis equipment with modified sterilised inserts to create a pulsatile hypothermic perfusion system. With this system, 41 NHBD kidneys were perfused for up to 8 h; their intravascular renal resistance (IRVR), flow characteristics as well as glutathione S transferase (GST) measurements were performed to assess viability. This hypothermic pulsatile perfusion system is now an integral component of our NHBD programme.

Costs and Cost Analysis↗
PubMed2001

Expression of chemokine receptors CXCR1 and CXCR2 during cardiopulmonary bypass.

OBJECTIVE: This study investigated the effects of cardiopulmonary bypass on neutrophil expression of chemokine receptors, CXCR1 and CXCR2, and the beta2 integrin CD11b. METHODS: Ten patients undergoing coronary artery grafting with cardiopulmonary bypass were studied. Blood samples were collected preoperatively, before bypass, at termination of bypass, and 12 to 18 hours postoperatively. In vitro studies were performed on control subjects to determine changes in the surface expression of CXCR1, CXCR2, and CD11b on stimulation with interleukin 8. Receptor expression was measured by flow cytometry. Plasma levels of interleukin 8 from the patients were determined by enzyme-linked immunoassay. RESULTS: After bypass, CXCR2 expression fell by 66% (P <.0001) and remained low postoperatively (P <.0001). CXCR1 expression persisted at preoperative levels. CD11b expression increased significantly after bypass (P <.0001), returning to prebypass levels postoperatively. In vitro studies showed a dose-related fall of both CXCR1 (P <.0001) and CXCR2 expression (P <.0001) and a significant rise in CD11b expression (P <.0001). Plasma interleukin 8 increased significantly after bypass (P <.0001), remaining elevated 12 to 18 hours postoperatively (P =.02). Correlations between interleukin 8 levels and CXCR2 expression (P <.0001) and CD11b expression (P <.03) were demonstrated. CONCLUSIONS: CXCR2 expression is significantly down-regulated after bypass; in contrast, CXCR1 expression remains unchanged. In addition, whereas interleukin 8 is an important determinant of both CXCR1 and CXCR2 expression in vitro, it only correlates with CXCR2 and CD11b expression in vivo. This has implications in the search for antagonists against CXC chemokines and their receptors.

Cardiopulmonary Bypass↗
PubMed2000

The trouble with kidneys derived from the non heart-beating donor: a single center 10-year experience.

BACKGROUND: The demand for renal transplantation has increasingly outstripped the supply of donor organs especially over the past 10 years. Although related and unrelated live donation is being promoted as one option for increasing the donor pool, it is unlikely that this will in itself be able to bridge the gap. Non-heart beating donors (NHBD) can provide an alternative supply of organs, which should substantially increase the donor pool. METHODS: In Newcastle, NHBD kidneys have been used for transplantation for a period of 10 years. In the early period (1988-1993) excellent results were obtained (90.5% success); however, these donors were controlled NHBD, Maastricht category III. In the second phase (1994-1998) increasing numbers of donors were obtained from the Accident and Emergency Department unit. These were failed resuscitation for cardiac arrest (category II). The rates of success in this period were poor (45.5% success) and the program was halted. The third phase of the program used machine perfusion of the kidneys and glutathione S transferase enzyme analysis to assess viability. RESULTS: Using such approaches renal transplants from largely category II donors produced a success rate of 92.3% which was significantly better than the phase II period of the program (P=0.023, Fisher two-tail test). CONCLUSION: Machine perfusion and viability assessment of NHB kidneys in phase III of the program has increased our donor pool as well as improved the graft survival. This is particularly relevant for the use of the category II NHB donor where the incidence of primary nonfunction was high, illustrated by phase II where machine perfusion/viability assessment was not used.

Adult↗
PubMed2000

Comparative antioxidant potential of anaesthetics and perioperative drugs in vitro.

We have investigated the comparative antioxidant capacity of a range of anaesthetics (inhaled and intravenous) and perioperative neurosurgical drugs (at clinically relevant concentrations) using different radical species and assay methods in vitro. The highest levels of antioxidant activity against the ABTS(.+) radical were obtained with propofol (100 mmol/LTE) and dopamine (1080 mmol/LTE), respectively. However, only dopamine (12 mmol/l) showed antioxidant activity in protecting proteins in normal brain tissue from oxidative damage (assessed via SDS-PAGE analysis) induced by OH(.) or O(2)(-.) generated radiolytically in vitro. Neither dopamine nor propofol showed antioxidant activity against O(2)(-.) generated chemically via reaction between xanthine and xanthine oxidase in vitro. From these data, together with data on the relative antioxidant properties of anaesthetics/drugs obtained by other research groups which we have reviewed, we conclude that the apparent antioxidant activity of a given compound may depend entirely on the free radical species and/or the method of generation or assay employed. Finally, we suggest that on the basis of data obtained showing protection of brain proteins from oxidative damage induced by OH(.), or O(2)(-.) in vitro, further investigation into the in vivo antioxidant therapeutic potential of dopamine (or its analogues) on neurosurgical patients may be warranted.

Anesthetics, Inhalation↗
PubMed2000

Comparison of proteolytic enzymes and glutathione S-transferase levels in non-heart-beating donors' (NHBD) kidney perfusates.

UNLABELLED: In order to identify biochemical markers of kidney damage prior to transplantation, we determined the levels of activity of a range of proteolytic enzymes in kidney perfusate samples from non-heart-beating donor (NHBD) cases. Urinary protease activities have been described as indices of kidney damage in renal disease; their potential as markers of tissue damage in kidneys before transplantation has not been assessed. In an attempt to identify additional/improved biochemical markers, the present study compared the levels of total glutathione S-transferase (GST) with corresponding levels of several proteolytic enzymes in perfusate fluid from machine perfused NHBD kidneys. Proteases were selected to represent factors that may influence enzyme efflux, such as intracellular localization or molecular size. METHODS: Perfusate samples were obtained over an 8-hour period from machine-preserved NHBD kidneys. Protease activities in these samples were determined by fluorometric assays and comparison made with total GST activity. Individual proteases were analysed in the transplanted and non-transplanted kidney groups (discarded on the basis of other viability parameters). RESULTS: A correlation between protease activity and total GST was obtained for only leucyl- and pyroglutamyl aminopeptidase. Furthermore, in the transplanted group, it was possible to set nominal upper limits of activity for alanyl-arginyl- and dipeptidyl IV-aminopeptidase (AP). In the non-transplanted kidney group protease levels were increased above "normal" upper limits for the same enzyme types. By the use of alanyl AP it was possible to discriminate 75% of unsuitable kidneys discarded by the use of other criteria. CONCLUSION: The lack of correlation between total GST and protease activity for most of the enzymes investigated and alanyl AP levels in perfusate samples could be related to differences in cellular localisation, suggesting that assays of alanyl AP may give complimentary biochemical information relating to kidney tissue damage. Quantification of alanyl AP in machine perfusate samples may be a valuable additional independent biomarker of tissue damage.

Endopeptidases↗
PubMed1991

Disparity between apolipoprotein E phenotypes and genotypes (as determined by polymerase chain reaction and oligonucleotide probes) in patients with non-insulin-dependent diabetes mellitus.

Apolipoprotein (apo) E phenotype and genotype frequencies, due to allelic variation at amino acids 112 and 158, have been investigated in 95 Caucasian non-insulin dependent diabetic patients (NIDDM). Phenotypes were determined by one-dimensional isoelectric focussing (IEF). In this sample, the frequency of the epsilon 2 allele was higher (0.122) and the frequency of the epsilon 4 allele lower (0.101) than previously reported in Caucasian populations (P less than 0.05). Genotypes were assigned using the technique of polymerase chain reaction and allele specific oligonucleotide probes. By contrast, the frequencies of the alleles determined by genotyping was similar to previously reported in Caucasian populations (apo epsilon 2, 0.095; epsilon 3, 0.758; epsilon 4, 0.147; P greater than 0.1). It is possible that in patients with NIDDM post-translational modification of apo E may lead to disparities, with phenotypes being unrepresentative of allelic variation at this gene locus.

Aged↗
PubMed1989

Apolipoprotein (apo) E genotypes by polymerase chain reaction and allele-specific oligonucleotide probes: no detectable linkage disequilibrium between apo E and apo CII.

Allelic sequence variation in the apolipoprotein (apo) E gene has been analysed by means of synthetic oligonucleotide probes that detect single base pair substitutions in the codons for amino acid positions 112 and 158, substitutions that are responsible for the common isoforms. Use of the polymerase chain reaction procedure to amplify a sequence of 330 base pairs of the human apo E gene has permitted the development of a robust method for apo E genotyping. This technique has been used to determine the apo E genotype in 95 individuals in whom the genotype for an apo CII TaqI restriction fragment length polymorphism has also been determined. No strong linkage disequilibrium between the two gene loci was detected. This suggests that the metabolic effects of variation in the apo E and apo CII genes, as detected by the polymorphisms used here, would operate in a statistically independent manner.

Adult↗
PubMedDate not supplied

Plasma fibrinogen levels and fibrinogen genotype in non-insulin dependent diabetics.

The association between plasma fibrinogen levels, fibrinogen genotype, and the development of macrovascular disease was studied in 100 patients with non-insulin dependent diabetes mellitus (NIDDM). The mean plasma fibrinogen levels in patients with macrovascular disease was higher than those without, although the difference was not statistically significant (3.67 g l-1, and 3.43 g l-1, respectively). The frequency of the rare allele of the fibrinogen gene DNA polymorphism detected with the restriction enzyme Bc1I was slightly higher in the group of patients with disease, but the difference was not statistically significant (0.20 vs 0.16). The frequency of the TaqI polymorphism rare allele was the same in both groups (0.30 vs 0.31). However, the Bc1I polymorphism was strongly associated with plasma fibrinogen levels, with those patients heterozygous for the rare allele having mean levels 16 per cent higher than those lacking the allele (3.81 g l-1 vs 3.28 g l-1, p < 0.05). This data demonstrates that variation at the fibrinogen locus is involved in determining fibrinogen levels in patients with NIDDM, and suggests the possibility that fibrinogen genotype and plasma fibrinogen levels could be one of the factors making a small contribution to the development of macrovascular disease in diabetic patients.

Aged↗
PubMedDate not supplied

Variation in the apolipoprotein B gene and development of type 2 diabetes mellitus.

Several studies have demonstrated an association between variation in the apolipoprotein (apo) B gene, principally as detected by the XbaI and EcoRI restriction fragment length polymorphisms (RFLPs), and lipoprotein levels or cardiovascular disease. We have examined the frequency of the EcoRI and XbaI RFLPs of the apoB gene in 95 white Type 2 diabetic patients aged between 45 and 80 years in order to ascertain whether variation in this gene may be influencing the development of Type 2 diabetes and associated atherosclerosis through obesity. Neither of the two RFLPs had a significant association with clinically defined cardiovascular disease or with body mass index in our sample. However, while XbaI displayed no association with circulating levels of lipids, lipoproteins or apolipoproteins, the presence of the rare (R2) alele of EcoRI (absence of cutting site) was associated with significantly higher levels of circulating triglycerides. Furthermore, the EcoRI R2 allele was over-represented in the diabetic sample when compared to a healthy control group. Our findings support previous studies which have shown an effect of variation at the apoB gene on circulating lipid levels; additionally, variation in this gene may contribute to the development of Type 2 diabetes mellitus.

Aged↗