Search PubMed⌕ Search

Biomedical subjects

M J Chapman

Publications and source records attributed to M J Chapman.

At least 19 recordsLinked to original sources
PubMed2005

Septic shock and sepsis: a comparison of total and free plasma cortisol levels.

CONTEXT: Severe systemic infection leads to hypercortisolism. Reduced cortisol binding proteins may accentuate the free cortisol elevations seen in systemic infection. Recently, low total cortisol increments after tetracosactrin have been associated with increased mortality and hemodynamic responsiveness to exogenous hydrocortisone in septic shock (SS), a phenomenon termed by some investigators as relative adrenal insufficiency (RAI). HYPOTHESIS: Free plasma cortisol may correspond more closely to illness severity than total cortisol, comparing SS and sepsis (S). DESIGN: This was a prospective study. SETTING: This study took place in a tertiary teaching hospital. PATIENTS: Patients had SS (n = 45) or S (n = 19) or were healthy controls (HCs; n = 10). AIM: The aim of the study was to compare total with free cortisol, measured directly and estimated by Coolens' method, corticosteroid-binding globulin (CBG), and albumin in patients with SS (with and without RAI) and S during acute illness, recovery, and convalescence. RESULTS: Comparing SS, S, and HC subjects, free cortisol levels reflected illness severity more closely than total cortisol (basal free cortisol, SS, 186 vs. S, 29 vs. HC, 13 nmol/liter, P < 0.001 compared with basal total cortisol, SS, 880 vs. S, 417 vs. HC, 352 nmol/liter, P < 0.001). Stimulated free cortisol increments varied greatly with illness category (SS, 192 vs. S, 115 vs. HC, 59 nmol/liter, P = 0.004), whereas total cortisol increments did not (SS, 474 vs. S, 576 vs. HC, 524 nmol/liter, P = 0.013). The lack of increase in total cortisol with illness severity is due to lower CBG and albumin. One third of patients with SS (15 of 45) but no S patients met a recently described criterion for RAI (total cortisol increment after tetracosactrin < or = 248 nmol/liter). RAI patients had higher basal total cortisol (1157 vs. 756 nmol/liter; P = 0.028) and basal free cortisol (287 vs. 140 nmol/liter; P = 0.017) than non-RAI patients. Mean cortisol increments in RAI were lower (total, 99 vs. 648 nmol/liter, P < 0.001; free, 59 vs. 252 nmol/liter, P < 0.001). These differences were not due to altered CBG or albumin levels. Free cortisol levels normalized more promptly than total cortisol in convalescence. Calculated free cortisol by Coolens' method compared closely with measured free cortisol. CONCLUSIONS: Free cortisol is likely to be a better guide to cortisolemia in systemic infection because it corresponds more closely to illness severity. The attenuated cortisol increment after tetracosactrin in RAI is not due to low cortisol-binding proteins. Free cortisol levels can be determined reliably using total cortisol and CBG levels.

Adrenal Insufficiency↗
PubMed2005

Defective antioxidative activity of small dense HDL3 particles in type 2 diabetes: relationship to elevated oxidative stress and hyperglycaemia.

AIMS/HYPOTHESIS: Elevated oxidative stress, hyperglycaemia, and dyslipidaemia involving low levels of HDL particles are key proatherogenic factors in type 2 diabetes mellitus. We examined the relationship of oxidative stress, and the degree of glycaemia and triglyceridaemia, to antioxidative function of HDL particle subspecies in type 2 diabetes. SUBJECTS AND METHODS: Five HDL subfractions (2b, 2a, 3a, 3b, 3c) were isolated by density gradient ultracentrifugation from well-controlled type 2 diabetic subjects (n=20) and normolipidaemic, non-diabetic controls (n=10). Specific antioxidative activity (capacity to protect LDL from oxidation on a unit particle mass or on a particle number basis), chemical composition and enzymatic activities were measured in each subfraction. Systemic oxidative stress was assessed as plasma levels of 8-isoprostanes. RESULTS: Specific antioxidative activity of small dense HDL3b and 3c particles in diabetic patients was significantly diminished (up to -47%, on a particle mass or particle number basis) as compared with controls. Plasma 8-isoprostanes were markedly elevated (2.9-fold) in diabetic patients, were negatively correlated with both specific antioxidative activity of HDL3 subfractions and plasma HDL cholesterol (HDL-C) levels, and were positively correlated with glycaemia and triglyceridaemia. Paraoxonase 1 activity was consistently lower in diabetic HDL subfractions and was positively correlated with HDL3 antioxidative activity. The altered chemical composition of diabetic HDL3 subfractions (core cholesteryl ester depletion, triglyceride enrichment) was equally correlated with diminished antioxidative activity. CONCLUSIONS/INTERPRETATION: Antioxidative activity of small dense HDL is deficient in type 2 diabetes, is intimately linked to oxidative stress, glycaemia and hypertriglyceridaemia and primarily reflects abnormal intrinsic physicochemical properties of HDL particles.

Antioxidants↗
PubMed2005

Remnant lipoproteins and atherosclerosis.

A recently developed assay for quantification of remnant-like particle cholesterol has provided considerable evidence that reinforces the concept that elevated levels of plasma remnants are associated with increased cardiovascular disease in different populations and distinct patient groups. In this review, we provide a brief summary of the most recently published studies, emphasizing the clinical relevance of remnant analysis. We discuss recent evidence that sheds light on the mechanisms that may underlie the atherogenicity of remnant lipoproteins. Taken together, these data provide new insight into the significance of remnant lipoproteins in the onset and development of premature atherosclerosis.

Biomarkers↗
PubMed2005

Crisis management during anaesthesia: hypertension.

BACKGROUND: Hypertension occurs commonly during anaesthesia and is usually promptly and appropriately treated by anaesthetists. However, its recognition is dependent on correctly functioning and calibrated monitors. If it is not diagnosed and/or promptly corrected, it has the potential to cause significant morbidity and even mortality. OBJECTIVES: To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK" supplemented by a specific sub-algorithm for the management of hypertension occurring in association with anaesthesia. METHODS: The potential performance of this approach for each of the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. RESULTS: There were 70 reports of intraoperative hypertension among the first 4000 incidents reported to AIMS. Drug related causes accounted for 59% of all incidents. It was considered that, properly applied, this structured approach would have led to a quicker and/or better resolution of the problem in 21% of the cases. CONCLUSION: Once hypertension is identified and confirmed, its rapid control by the careful use of a volatile anaesthetic agent, intravenous opioids, or rapidly acting antihypertensives will usually avoid serious morbidity. If hypertension is unresponsive to the treatment recommended in the relevant sub-algorithm, an unusual cause such as phaeochromocytoma, carcinoid syndrome, or thyroid storm should be considered.

Algorithms↗
PubMed2005

Crisis management during anaesthesia: sepsis.

BACKGROUND: Anaesthesia with concurrent sepsis is risky, and involves consideration of possible organ dysfunctions-respiratory, cardiovascular, renal, and haematological--as well as ensuring that appropriate antibiotics are given after taking the necessary microbiological specimens. Because prompt attention needs to be paid to so many body systems, the place for a structured approach during anaesthesia for a septic patient was assessed. OBJECTIVES: To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK", supplemented by a specific sub-algorithm for sepsis, in the management of sepsis occurring in association with anaesthesia. METHODS: The potential performance of this structured approach for each of the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. RESULTS: Sepsis was identified as the primary problem in 13 of the first 4000 reports (<1%) to AIMS. The incidents reported generally occurred in sick patients; 70% were ASA status III or worse. The COVER ABCD algorithm provided a diagnosis and corrective manoeuvre in only 15% (2/13) of reported incidents, and the sepsis sub-algorithm provided adequate therapeutic strategies in a further 38% (5/13) of the incidents. Eight cases required the use of additional sub-algorithms for desaturation (30%), cardiac arrest (15%), hypotension (8%), and aspiration (8%). CONCLUSION: Sepsis involves a serious physiological stress upon multiple organ systems. The use of a structured approach involving a core algorithm and additional sub-algorithms as required provides a series of checklists that can successfully deal with the complex multiple and interrelating problems that these patients present.

Algorithms↗
PubMed2005

Crisis management during anaesthesia: pulmonary oedema.

BACKGROUND: Pulmonary oedema may complicate the perioperative period and the aetiology may be different from non-operative patients. Diagnosis may be difficult during anaesthesia and consequently management may be delayed. OBJECTIVES: To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK", supplemented by a specific sub-algorithm for pulmonary oedema, in its management occurring in association with anaesthesia. METHODS: The potential performance of this structured approach for each of the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. RESULTS: Pulmonary oedema was identified in 35 (<1%) of the first 4000 reports to AIMS. The most frequent presenting sign was hypoxia (46%) and the most specific sign was the presence of frothy sputum (23%). The core algorithm, although successful in the management of the initial physiological upset, was found to be inadequate for the ongoing management of pulmonary oedema. A specific sub-algorithm for the management of perioperative pulmonary oedema was devised, tested against the reports and would have been effective, if properly applied, in the management of all but one of the reported cases. CONCLUSION: Successful recognition and management of perioperative pulmonary oedema is likely with the application of the structured algorithm and specific sub-algorithm approach outlined in this study.

Algorithms↗
PubMed2005

Crisis management during anaesthesia: pneumothorax.

BACKGROUND: Pneumothorax is a potentially dangerous condition which may arise unexpectedly during anaesthesia. The diagnosis is one of exclusion, as initial changes in vital signs (cardiorespiratory decompensation and difficulty with ventilation) are non-specific, and other causes of such changes are more common, whereas local signs may be difficult to elicit, especially without full access to the chest. OBJECTIVES: To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK", supplemented by a specific sub-algorithm for pneumothorax, in the management of pneumothorax occurring in association with anaesthesia. METHODS: Reports of pneumothorax were extracted and studied from the first 4000 incidents reported to the Australian Incident Monitoring Study (AIMS). The potential performance of the structured approach, using the combination of algorithims described above for each of the relevant incidents, was compared with the actual management as reported by the anaesthetists involved. RESULTS: Pneumothorax was noted as a possible diagnosis in 65 reports; 24 cases had a confirmed pneumothorax, of which 17 were in association with general anaesthesia. It was considered that, correctly applied, the application of the algorithms would have led to earlier recognition of the problem and/or better management in 12% of cases. CONCLUSION: Any pneumothorax may become a dangerous tension pneumothorax with the application of positive pressure ventilation. Limited access to the chest during anaesthesia may compromise the diagnosis. Recognition of any preoperative predisposition to a pneumothorax (for example, iatrogenic or traumatic penetrating procedures around the base of the neck) and close communication with the surgeon are important. Aspiration diagnosis in suspected cases and correct insertion of a chest drain are essential for the safe conduct of anaesthesia and surgery.

Algorithms↗
PubMed2005

A novel technique for post-pyloric feeding tube placement in critically ill patients: a pilot study.

Delivery of enteral nutrition in critically ill patients is often hampered by gastric stasis necessitating direct feeding into the small intestine. Current techniques for placement of post-pyloric feeding catheters are complex, time consuming or both, and improvements in feeding tube placement techniques are required. The Cathlocator is a novel device that permits real time localisation of the end of feeding tubes via detection of a magnetic field generated by a small electric current in a coil incorporated in the tip of the tube. We performed a pilot study evaluating the feasibility of the Cathlocator system to guide and evaluate the placement of (1) nasoduodenal feeding tubes, and (2) nasogastric drainage tubes in critically ill patients with feed intolerance due to slow gastric emptying. A prospective study of eight critically ill patients was undertaken in the intensive care unit of a tertiary hospital. The Cathlocator was used to (1) guide the positioning of the tubes post-pylorically and (2) determine whether nasogastric and nasoduodenal tubes were placed correctly. Tube tip position was compared with data obtained by radiology. Data are expressed as median (range). Duodenal tube placement was successful in 7 of 8 patients (insertion time 12.6 min (5.3-34.4)). All nasogastric tube placements were successful (insertion time 3.4 min (0.6-10.0)). The Cathlocator accurately determined the position of both tubes without complication in all cases. The Cathlocator allows placement and location of an enteral feeding tube in real time in critically ill patients with slow gastric emptying. These findings warrant further studies into the application of this technique for placement of post-pyloric feeding tubes.

APACHE↗
PubMed2004

Relationship of circulating C-reactive protein levels to thyroid status and cardiovascular risk in hyperlipidemic euthyroid subjects: low free thyroxine is associated with elevated hsCRP.

The mechanism(s) by which low circulating levels of thyroid hormones may lead to development of premature atherosclerosis remain to be established. These mechanisms include indirect effects of thyroid hormones on cardiovascular risk factors such as plasma lipoproteins, homocysteine and fibrinogen. High-sensitivity C-reactive protein (hsCRP) has been identified as an independent predictor of cardiovascular events. We presently investigated the relationship between hsCRP and free thyroxine (FT4) levels in a large population of euthyroid hyperlipidemic patients (n=429, mean age: 47.1 years, 28% of current smokers). None of these subjects presented a recent history of infection or inflammatory disease and those taking drugs known to influence thyroid or hsCRP were excluded. Serum FT4 levels were measured by radioimmunoassay and CRP, by a high-sensitivity immunoassay. In the population of non-smokers, plasma FT4 levels were negatively and significantly correlated with those of hsCRP (r=-0.13, P=0.02). Significant correlations between FT4 levels and age (r=-0.16, P=0.003), glycemia (r=-0.14, P=0.01), and fibrinogen (r=-0.18, P=0.001) were equally observed. Upon division of the population on the basis of FT4 tertiles, the mean level of hsCRP was significantly higher in non-smoker patients with the lowest FT4 tertile as compared to those displaying the highest FT4 level (3.04mg/l versus 1.77mg/l, respectively, P<0.05). No correlation between FT4 levels and CRP was found in smokers.In conclusion, we demonstrate that hsC-reactive protein is significantly negatively correlated with free thyroxine levels in non-smoker hyperlipidemic patients, suggesting that low thyroxine levels in euthyroid hyperlipidemic subjects constitute a new biomarker of elevated cardiovascular risk.

Biomarkers↗
PubMed2003

Severe ethanol poisoning: a case report and brief review.

A case of severe ethanol toxicity is described where a patient was admitted pulseless, apnoeic and deeply unconscious after ingesting a full bottle (1 litre) of 'methylated spirits' The initial blood ethanol level was 1.127 g/dL. The patient was rapidly intubated and resuscitated with fluids and inotropic agents. Renal replacement therapy was initiated and a rapid reduction in the initial blood ethanol level occurred. Twenty-one hours after her admission she was conscious and cooperative and was discharged from the intensive care unit without any clinical evidence of brain injury. Ethanol toxicity is common although ethanol poisoning leading to death is rare. Nevertheless, severe toxicity can cause medullary paralysis with respiratory failure and death. Rapid resuscitation and, in severe cases, renal replacement therapy may be warranted as the outlook for patients who recover is excellent.

Journal Article↗
PubMed2002

A constellation of cardiovascular risk factors is associated with hepatic enzyme elevation in hyperlipidemic patients.

Abnormal circulating levels of hepatic enzymes are frequently found in subjects displaying hyperlipidemia or obesity or both. At present, there is a paucity of information on the principal cardiovascular risk factors that are associated with elevated plasma levels of hepatic enzyme activity in hyperlipidemic patients. We analyzed the potential relationships between serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) and cardiovascular and metabolic risk factors in a cohort of 8,501 men and women referred to our outpatient clinic for hyperlipidemia by their general practitioner. In this cohort, 27.6% of patients displayed serum levels of ALT above the upper limit of normal values. Both men and women who exhibited ALT levels superior to the upper limit of the normal range had elevated systolic (SBP) and diastolic blood pressure (DBP), body mass index (BMI), alcohol intake, and serum levels of blood glucose, uric acid, total cholesterol, and triglycerides (P <.0035 for all parameters). In a multivariate analysis, BMI, uric acid, and blood glucose remained significantly associated with ALT levels in men and women. We conclude that cardiovascular and metabolic features characterizing the plurimetabolic syndrome, including serum uric acid levels, are associated with significant elevation of hepatic enzyme activities. Because these abnormalities may not only be reversible but also associated with a poor prognosis, further studies are needed to identify those dyslipidemic patients who are at risk for the development of severe hepatic tissue damage.

Adult↗
PubMed2001

Apolipoprotein A-II/A-I ratio is a key determinant in vivo of HDL concentration and formation of pre-beta HDL containing apolipoprotein A-II.

Overexpression of human apolipoprotein A-II (apo A-II) in mice induced postprandial hypertriglyceridemia and marked reduction in plasma HDL concentration and particle size [Boisfer et al. (1999) J. Biol. Chem. 274, 11564-11572]. We presently compared lipoprotein metabolism in three transgenic lines displaying plasma concentrations of human apo A-II ranging from normal to 4 times higher, under ad libitum feeding and after an overnight fast. Fasting dramatically decreased VLDL and lowered circulating human apo A-II in transgenic mice; conversely, plasma HDL levels increased in all genotypes. The apo A-I content of HDL was inversely related to the expression of human apo A-II, probably reflecting displacement of apo A-I by an excess of apo A-II. Thus, the molar ratios of apo A-II/A-I in HDL were significantly higher in fed as compared with fasted animals of the same transgenic line, while endogenous LCAT activity concomitantly decreased. The number and size of HDL particles decreased in direct proportion to the level of human apo A-II expression. Apo A-II was abundantly present in all HDL particles, in contrast to apo A-I mainly present in large ones. Two novel findings were the presence of pre-beta migrating HDL transporting only human apo A-II in the higher-expressing mice and the increase of plasma HDL concentrations by fasting in control and transgenic mice. These findings highlight the reciprocal modifications of VLDL and HDL induced by the feeding-fasting transition and the key role of the molar ratio of apo A-II/A-I as a determinant of HDL particle metabolism and pre-beta HDL formation.

Animals↗
PubMed2001

Platelet-activating factor acetylhydrolase and transacetylase activities in human plasma low-density lipoprotein.

In this study, we demonstrate the presence of a transacetylase activity in human plasma low-density lipoprotein (LDL) that transfers short-chain fatty acids from platelet-activating factor (PAF) and its close ether- and ester-linked analogues to ether/ester-linked lysophospholipids (lyso-PL). We show evidence that both PAF acetylhydrolase (PAF-AH) and transacetylase activities are inhibited to the same extent by serine esterase inhibitors, are resistant to heat treatment, and exhibit identical distributions in lipoprotein classes and in LDL subfractions. Additionally, the competitive inhibition of PAF-AH by lyso-PL, and the evidence that the recombinant PAF-AH also showed a similar transacetylase activity, suggest that PAF-AH is responsible for both activities. Using PAF as a donor molecule and lyso-PAF (1-O-alkyl-sn-glycero-3-phosphocholine) as an acceptor, the transacetylase activity showed typical allosteric kinetics, due to the positive co-operativity of the substrates, with apparent Vmax=19.6+/-3.4 nmol/min per mg of protein, apparent h=2.0+/-0.3 and apparent [S]0.5=9.4+/-2.3 microM at saturation for the concentration of lyso-PAF. The substrate specificity of the donor molecules was decreased by increasing the chain length of the acyl moiety in the sn-2 position of the glycerol. The ether linkage in the sn-1 position of the substrate was 30% more effective than the ester bond; cholesteryl acetate was inactive as an acetyl donor. The two acceptors tested, lyso-PAF and the ester-linked lyso-PC (1-acyl-sn-glycero-3-phosphocholine), showed similar specificity. Addition of exogenous lyso-PAF induced the transient formation of PAF-like aggregating activity predominantely in small dense LDL subfractions upon oxidation. We conclude that PAF-AH possesses both transacetylase and acetylhydrolase activities which remove PAF and its ether-linked analogues from LDL particles upon LDL oxidation. However, in atherogenic small dense LDL-5 particles, the transacetylase activity may acetylate extracellular lyso-PAF into biologically active PAF.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

Functional analysis of the chimpanzee and human apo(a) promoter sequences: identification of sequence variations responsible for elevated transcriptional activity in chimpanzee.

Lp(a) concentrations vary considerably among individuals and are primarily determined by the apo(a) gene locus. We have previously shown that mean plasma Lp(a) levels in the chimpanzee are significantly higher than those observed in humans (Doucet, C., Huby, T., Chapman, J., and Thillet, J. (1994) J. Lipid Res 35, 263-270). To evaluate the possibility that this difference may result from a high level of expression of chimpanzee apo(a), we cloned and sequenced 1.4 kilobase (kb) of the 5'-flanking region of the gene and compared promoter activity to that of its human counterpart. Sequence analysis revealed 98% homology between chimpanzee and human apo(a) 5' sequences; among the differences observed, two involved polymorphic sites associated with Lp(a) levels in humans. The TTTTA repeat located 1.3 kb 5' of the apo(a) gene, present in a variable number of copies (n = 5-12) in humans, is uniquely present as four copies in the chimpanzee sequence. The second position concerns the +93 C>T polymorphism that creates an additional ATG start codon in the human apo(a) gene, thereby impairing translation efficiency. In chimpanzee, this position did not appear polymorphic, and a base difference at position +94 precluded the presence of an additional ATG. In transient transfection assays, the chimpanzee apo(a) promoter exhibited a 5-fold elevation in transcriptional activity as compared with its human counterpart. This marked difference in activity was maintained with either 1.4 kb of 5' sequence or the minimal promoter region -98 to +141 of the human and chimpanzee apo(a) genes. Using point mutational analyses, nucleotides present at positions -3, -2, and +8 (relative to the start site of transcription) were found to be essential for the high transcription efficiency of the chimpanzee apo(a) promoter. High transcriptional activity of the chimpanzee apo(a) gene may therefore represent a key factor in the elevated plasma Lp(a) levels characteristic of this non-human primate.

Animals↗