Non-infarctual ST elevation and acute cardiopulmonary failure in carbon monoxide poisoning: a case report.

OBJECTIVE: Carbon monoxide is produced by the incomplete combustion of organic fuel. In the United States, it is responsible for about 500 deaths annually. Increased carboxyhemoglobin concentration and hypoxia disrupt cardiac myocyte integrity and cause dysrhythmias, acute cardiac failure and coronary artery disease. We described a case of a patient with CO-poisoning and ST elevation at ECG precordial leads who developed severe transient heart failure. CASE PRESENTATION: A 57-year-old man was admitted to the emergency department for acute carbon monoxide poisoning that led to respiratory and cardiac failure. The electrocardiogram showed ST elevation in precordial leads, but the coronary angiography was normal. The patient was successfully treated and discharged. Three days later he was readmitted for similar symptoms and subsequently died. We hypothesize that the ECG findings were related to transient coronary vasospasm due to CO poisoning and that acute respiratory and cardiac failure related to carbon monoxide toxicity caused death. CONCLUSIONS: The management of patients poisoned by carbon monoxide requires early identification and intensive treatment and a careful evaluation of the home environment prior to discharge. ST elevation in such patients may be related to coronary vasospasm.

Pro-protein convertase subtilisin/kexin 9 concentrations correlate with coronary artery disease atheroma burden in a Pakistani cohort with chronic chest pain.

OBJECTIVE: To determine the relationship between proprotein convertase subtilisin kexin 9 (PCSK9) levels and atheroma burden in Pakistanis presenting to an ambulatory centre with chest pain. METHODS: A prospective matched case-control study of 400 patients selected for presence/absence of angiographic disease referred between 2001 and 2003. A comprehensive cardiovascular disease risk factor profile was assessed including demographics, environmental and biochemical risk factors including insulin resistance and PCSK-9 levels. Coronary atheroma burden was quantified by Gensini score. RESULTS: In this population, PCSK-9 levels were weakly correlated (r = 0.23) with male gender (p = 0.06) and number of diabetes years (p = 0.09), and inversely with log10 of lipoprotein (a) concentration (p = 0.07) but not LDL-C. In multiple regression analysis, Gensini score was associated with age (p = 0.002), established angina (p = 0.001), duration of diabetes (p = 0.05), low HDL-C (p < 0.001), lipoprotein (a) (p = 0.01), creatinine (p < 0.001), C-Reactive Protein (p = 0.02) and PSCK-9 (p = 0.05) concentrations. PCSK9 added to the regression model. Neither total cholesterol nor LDL-C were significant risk factors in this study. CONCLUSIONS: Proprotein convertase subtilisin kexin 9 concentrations are correlated with atheroma burden in Indian Asian populations from the sub-continent, not taking statin therapy, independent of LDL-C or other CVD risk factors.

Angiographic coronary artery disease and high-sensitivity troponin-T in a native Pakistani cohort presenting with chronic chest pain.

OBJECTIVE: To determine the relationship between troponin-T levels and atheroma burden in Pakistanis presenting to an ambulatory centre with chest pain. METHODS: A prospective case-control study of 400 patients selected for presence/absence of angiographic disease referred between 2001 and 2003. A comprehensive cardiovascular disease (CVD) risk factor profile was assessed including demographics, environmental and biochemical risk factors including insulin resistance and troponin-T levels. Coronary atheroma burden was quantified by Gensini score. RESULTS: Clinically significant elevated troponin-T levels (> 30 pmol/l) were found in 40 patients (10%) with equal numbers in groups selected with or without angiographic disease. Troponin-T elevation (> 13 pmol/l) was present in 59 vs. 47 patients (30% vs. 24%; p = 0.04). Troponin-T levels did not correlate with any measured demographical, environmental, drug therapy or biochemical risk factor. No difference was found in concentrations of lipids, apolipoproteins, insulin resistance, C-reactive protein or sialic acid in cohorts stratified by troponin-T concentrations. In univariate analysis comparing patients with high (> 30 pmol/l) and low troponin-T levels (< 13 pmol/l) higher plasma total protein (91 g/l vs. 85 g/l; p = 0.01), increased immunoglobulin levels (41 g/l vs. 36 g/l; p = 0.02) and prevalence of hyperparathyroidism (40% vs. 21%; p = 0.04) were associated with higher troponin-T concentrations. CONCLUSIONS: This study shows that measurement of troponin-T is not an alternative to imaging in an Indian asian population, but that it does identify a separate potentially high-risk population that would not be identified by the use of imaging alone which is potentially at higher risk of CVD events.

Insulin resistance phenotypes and coronary artery disease in a native Pakistani cohort.

OBJECTIVE: To determine the relationship between insulin resistance (IR) and atheroma burden in Pakistanis. METHODS: A prospective case-control study of 400 patients selected for the presence/absence of angiographic disease. Coronary atheroma burden was quantified and IR and cardiovascular risk factors were measured. RESULTS: The patients were divided into two groups by QuickI score. Waist circumference (90 +/- 10 vs. 90 +/- 9 cm; p = 0.7) was similar but the groups differed in body mass index (26.5 +/- 3.7 vs. 24.2 +/- 3.5 kg/m(2); p < 0.001) and waist:hip ratio (0.94 +/- 0.09 vs. 0.90 +/- 0.06; p < 0.001). Lipid parameters showed similar high-density lipoprotein cholesterol (HDL-C) (0.77 +/- 0.23 vs. 0.82 +/- 0.22 mmol/l; p = 0.1) differences in triglycerides [1.32 (0.08-3.98) vs. 1.12 (0.37-3.61) mmol/l; p = 0.01], but no difference in low-density lipoprotein cholesterol (LDL-C) (2.75 +/- 1.00 vs. 2.90 +/- 0.94 mmol/l; p = 0.14). In insulin-resistant patients C-reactive protein (CRP) [6.8 (0.3-175.1) vs. 3.9 (0.2-57.9) mg/l: p < 0.001], sialic acid (82 +/- 14 vs. 77 +/- 15 mg/l; p < 0.001) aspartate transaminase [24 (7-171) vs. 21 (7-83) IU/l; p < 0.001] and gamma-glutamyl transferase [27 (8-482) vs. 21 (7-168) IU/l; p = 0.005] levels were increased. In insulin-resistant patients (n = 187), coronary artery disease (CAD) burden correlated (r = 0.55) with age (beta = 1.62; p < 0.001), HDL-C (beta = -53.2; p < 0.001), lipoprotein (a) (beta = 11.4; p = 0.007), smoking (beta = 7.98; p = 0.004), CRP (beta = 6.06; p = 0.03) and QuickI index (beta = -146; p = 0.04). In contrast in insulin-sensitive patients (n = 178) CAD burden (r = 0.46) correlated with LDL-C (beta = 10.0; p = 0.02), CRP (beta = 7.13; p = 0.03), HDL-C (beta = -38.1; p = 0.03), and weakly with age (beta = 0.73; p = 0.07) and smoking (beta = 5.52; p = 0.09). CONCLUSIONS: Indian Asians show a dichotomous insulin-resistance phenotype. Atheroma is associated with low HDL-C and inflammation associated in all but LDL-C is a factor in the insulin sensitive in contrast to age and extent of IR in the insulin resistant.

Erectile dysfunction and statin treatment in high cardiovascular risk patients.

Erectile dysfunction (ED) has been associated with risk factors for atherosclerosis. Medications used for atherosclerosis have also been implicated in ED. The aim of this study is to investigate the relationship of erectile function to cardiovascular risk factors and specific drug therapies before and after 6 months of statin therapy. In this prospective observational study, International Index of Erectile Function (IIEF) scores were measured in 93 men attending cardiovascular risk clinics. Cardiovascular risk factors and drug therapies were assessed prior to initiation and after 6 months of statin therapy. Prior to statin therapy, the median IIEF score was 21 (range 0-25), and 57% had impairment of erectile function. After statin therapy, IIEF scores were reduced to 6.5 (range 0-25) (p < 0.001), and 22% experienced new onset ED. Before statin therapy no correlation was observed between IIEF score and any individual cardiovascular risk factor. After 6 months of statin therapy, correlations were observed between lower IIEF scores (r = 0.62; p < 0.001) and age and diabetes and weakly with smoking. Differences in dose, relative efficacy or relative lipophilicity of statin prescribed showed no correlation with change in IIEF score. This study suggests ED following statin therapy is more likely in patients with severe endothelial dysfunction due to established cardiovascular risk factors including age, smoking and diabetes.

Metabolic syndrome and risk of coronary heart disease in a Pakistani cohort.

OBJECTIVE: To assess the relation of the metabolic insulin resistance syndrome (M-IRS) with coronary heart disease (CHD) in Pakistani patients. SUBJECTS: 200 patients with angiographic disease (CHD(+)) matched with 200 patients with chest pain without occlusive disease (CHD(-)). DESIGN: Prospective case-control study. SETTING: Tertiary referral cardiology unit in Pakistan. RESULTS: M-IRS was present in 37% of CHD(+) versus 27% of CHD(-) patients by criteria for white patients or 47% versus 42%, respectively, by Asian criteria (p < 0.001). After adjustment for other risk factors, M-IRS was not a significant predictor for CHD or angiographic disease. Age (p = 0.03), smoking (p < 0.001), diabetes-years (p = 0.003), sialic acid (p = 0.01), and creatinine (p = 0.008) accounted for the excess risk of CHD. Similarly, age (p = 0.005), creatinine (p < 0.001), cigarette pack-years (p = 0.02), diabetes-years (p = 0.003), and sialic acid (p = 0.08) were predictors of greater angiographic disease. M-IRS differed between Pakistani and white patients, as waist circumference correlated weakly (r = -0.03-0.08, p = 0.45-0.52) with triglycerides, high density lipoprotein cholesterol, systolic blood pressure, or glucose. Sialic acid was the only inflammatory marker associated with M-IRS. CONCLUSIONS: Despite strong associations between individual risk factors associated with M-IRS and a univariate association between M-IRS and CHD in native Pakistanis, the principal discriminant risk factors in this group are age, smoking, inflammation, diabetes-years, and impaired renal function. The poor sensitivity of M-IRS for CHD reflects the high underlying prevalence of M-IRS, thus reducing sensitivity, confounding by other urban lifestyle traits, or a lack of association of waist circumference with M-IRS risk factors. The definition of M-IRS may have to be revised to increase its power as a discriminant risk factor for CHD in Pakistani populations.

Ezetimibe-induced hyperlipidaemia.

Ezetimibe is intestinally active cholesterol absorption inhibitor used to reduce low-density lipoprotein-cholesterol levels. This case report describes a novel side effect with this agent: ezetimibe-induced hyperlipidaemia in a patient with statin intolerance and familial combined hyperlipidaemia. Ezetimibe therapy induced an asymptomatic 770% increase in triglycerides (TGs) (3.51-27.1 mmol/l) and a 190% increase in total cholesterol (9.8-18.5 mmol/ 1) secondary to an increase (4.6-25.9 micromol/l; 560%) in hepatic cholesterol (lathosterol) synthesis. This lipid profile resolved 9 months after cessation of ezetimibe therapy. This report shows that ezetimibe may have long-lasting effects in man far exceeding its plasma half-life and that ezetimibe monotherapy can induce a large increase in hepatocyte very-low-density lipoprotein synthesis in rare individuals with a consequent mixed hyperlipidaemia or possibly hypercholesterolaemia depending on the metabolism and clearance of TG-rich lipoproteins.

Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection.

AIMS/HYPOTHESIS: Heterozygous mutations in the gene of the transcription factor hepatocyte nuclear factor 4alpha (HNF-4alpha) are considered a rare cause of MODY with only 14 mutations reported to date. The description of the phenotype is limited to single families. We investigated the genetics and phenotype of HNF-4alpha mutations in a large European Caucasian collection. METHODS: HNF-4alpha was sequenced in 48 MODY probands, selected for a phenotype of HNF-1alpha MODY but negative for HNF-1alpha mutations. Clinical characteristics and biochemistry were compared between 54 HNF-4alpha mutation carriers and 32 familial controls from ten newly detected or previously described families. RESULTS: Mutations in HNF-4alpha were found in 14/48 (29%) probands negative for HNF-1alpha mutations. The mutations found included seven novel mutations: S34X, D206Y, E276D, L332P, I314F, L332insCTG and IVS5nt+1G>A. I314F is the first reported de novo HNF-4alpha mutation. The average age of diagnosis was 22.9 years with frequent clinical evidence of sensitivity to sulphonylureas. Beta cell function, but not insulin sensitivity, was reduced in diabetic mutation carriers compared to control subjects (homeostasis model assessment of beta cell function 29% p<0.001 vs controls). HNF-4alpha mutations were associated with lower apolipoprotein A2 (p=0.001), A1 (p=0.04) and total HDL-cholesterol (p=0.02) than in control subjects. However, in contrast to some previous reports, levels of triglycerides and apolipoprotein C3 were normal. CONCLUSIONS/INTERPRETATION: HNF-4alpha mutations are common when no HNF-1alpha mutation is found in strictly defined MODY families. The HNF-4alpha clinical phenotype and beta cell dysfunction are similar to HNF-1alpha MODY and are associated with reduced apolipoprotein A2 levels. We suggest that sequencing of HNF-4alpha should be performed in patients with clinical characteristics of HNF-1alpha MODY in whom mutations in HNF-1alpha are not found.

Cardiovascular risk in women with polycystic ovarian syndrome (PCOS).

AIMS: Studies have suggested that polycystic ovary syndrome (PCOS) is associated with increased cardiovascular risk. The aim of this study was to examine cardiovascular risk profiles in women with PCOS compared with healthy age and weight matched control subjects using novel biochemical and biophysical markers. METHODS: After ethics committee approval, 11 women with PCOS and 12 controls were recruited (mean age, 32; SD, 6.5 years; mean body mass index (BMI), 33.1; SD, 5.9 kg/m2). Serum was analysed for lipid and lipoprotein profile (total and high density lipoprotein cholesterol, triglycerides, apolipoprotein B-100, apolipoprotein A1, lipoprotein (a)), and sialic acid, fibrinogen, homocysteine, and C reactive protein (CRP) concentrations. Endothelial function was also assessed by a standard venous occlusion plethysmography technique to measure reactive hyperaemic forearm blood flow (RH), and expressed as per cent increase from baseline. RESULTS: There were no significant differences in glucose, lipid, or lipoprotein concentrations between the two groups. Furthermore, sialic acid (PCOS: mean, 70.5; SD, 149 mg/litre; controls: mean, 71.3; SD, 112 mg/litre), fibrinogen (PCOS: mean, 3.1; SD, 1.0 g/litre; controls: mean, 3.3; SD, 0.7 g/litre), CRP (PCOS: mean, 4.6; SD, 4.2 mg/litre; controls: mean, 5.41 SD, 5.5 mg/litre), and RH (PCOS: mean, 158.7; SD, 135.5%; controls: mean, 200.1; SD, 114.2%) were similar. CONCLUSIONS: There were no differences in surrogate markers of the processes linked to enhanced cardiovascular risk between patients with PCOS and weight matched controls.

The response of serum apolipoprotein H to an oral fat load.

BACKGROUND: We tested the hypothesis that serum apolipoprotein H (apo H) concentration increases after an oral fat load. Such a study would give valuable insight into whether apo H was influenced by the postprandial state. METHODS: Ten male subjects aged 24-48 years were fed 62.5 g of total fat (saturates 12 g, monounsaturates 35.3 g, polyunsaturates 12.5 g). Venous blood was sampled hourly for 5 h post-oral fat load. RESULTS: No significant change in serum apo H concentration occurred following the oral fat load. However, serum apo H in the baseline samples correlated significantly with subject body mass index (r = 0.683, P < 0.05), body fat mass (r = 0.778, P < 0.01), lean body mass (r = 0.693, P < 0.05), serum triglyceride (r = 0.732, P < 0.02), serum insulin (r = 0.808, P < 0.01) and insulin resistance index (r = 0.794, P < 0.01). In stepwise multiple linear regression model, with serum apo A1, apo B, lipoprotein(a), total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, plasma glucose and insulin and apo H as the dependent variable, insulin remained in the model (r = 0.81, P < 0.01). Conversely, with body mass index, body fat mass, lean body mass and waist/hip ratio in the model and apo H as dependent variable, only body fat mass remained in the model (r = 0.78, P < 0.01). CONCLUSIONS: Serum apo H may be involved in insulin resistance and relates to various indices of adipose tissue, including body fat mass. However, serum apo H concentrations do not significantly change postprandially.

Effect of moxonidine on lipid subfractions in patients with hypertension.

Moxonidine is centrally acting imidazoline type-1 receptor agonist that significantly lowers blood pressure and has some insulin-sensitising actions. Its effects on plasma lipid profiles are uncertain. This study examined the effects of moxonidine on detailed lipid and lipoprotein profiles in 12 patients with hypertension and type 2b Fredricksen hyperlipidaemia. Treatment with moxonidine in six patients who completed the study resulted in a 10/5 mmHg reduction in 24-h ambulatory blood pressure (p = 0.01). A significant reduction in total and low-density-lipoprotein cholesterol (LDL-C) of 10% (p = 0.04) and 18% (p = 0.03), respectively, was seen. Triglycerides were reduced non-significantly by 23%, and high-density-lipoprotein cholesterol (HDL-C) was increased by 16%. There were no significant changes in apolipoprotein (apo) A-1 and B concentrations. No significant shifts were seen in HDL-C, LDL-C, very-low-density-lipoprotein cholesterol (VLDL-C) or apolipoprotein peak positions with therapy. Analysis of area under curve for each subfraction showed that moxonidine therapy resulted in a redistribution within the apoB profile. A slight non-significant reduction in VLDL apoB was seen. There was a reduction in the dense LDL apoB peak (p = 0.02) but less in the buoyant LDL apoB peak (p = 0.17) with a countervailing increase in LDL-C in the buoyant fraction (p = 0.01). The HDL-C and apoA-1 profile showed a shift from dense HDL apoA-1 (p = 0.01) to a buoyant HDL apoA-1sub-species (p = 0.01). These changes are consistent with a tendency for moxonidine to improve atherogenic lipid and lipoprotein profiles by actions on insulin-sensitisation and possibly through a direct cholesterol-reducing effect as seen with other imidazoles.

Effects of growth hormone (GH) replacement therapy on low-density lipoprotein apolipoprotein B100 kinetics in adult patients with GH deficiency: a stable isotope study.

GH replacement therapy has been shown to improve the dyslipidemic condition in a substantial proportion of patients with adult GH deficiency. The mechanisms are not yet fully elucidated. Low-density lipoprotein (LDL) apolipoprotein B100 (apoB) formation and catabolism are important determinants of plasma cholesterol concentrations. This study examined the effect of GH replacement therapy on LDL apoB metabolism using a stable isotope turnover technique. LDL apoB kinetics was determined in 13 adult patients with GH deficiency before and after 3 months GH/placebo treatment in a randomized, double-blind, placebo-controlled study. LDL apoB (13)C-leucine enrichment was determined by isotope-ratio mass spectrometry. Plasma volume was assessed by standardized radionuclide dilution technique. GH replacement therapy significantly decreased LDL cholesterol, LDL apoB concentrations, and LDL apoB pool size compared with placebo. Compared with baseline, GH replacement therapy resulted in a significant increase in plasma volume and fractional catabolic rate, whereas LDL formation rate remained unchanged. LDL lipid content did not significantly change after GH and placebo. This study suggests that short-term GH replacement therapy decreases the LDL apoB pool by increasing removal of LDL particles without changing LDL composition or LDL apoB production rate. In addition, it is possible that the beneficial effects of GH on the cardiovascular system contribute to these findings.

Metastasis in pleural mesothelioma. Immunohistochemical markers for disseminated disease.

AIMS: To examine 13 cases of mesothelioma with metastases and compare these with 29 biopsy samples of patients without metastases. Metastatic disease was defined as tumour in which tumour appeared in a different cavity/tissue of the body and which showed no direct spread. Consequently, mediastinal nodal and parenchymal lung spread was excluded. METHODS AND RESULTS: Standard sections were prepared and stained according to the manufacturers' protocols. The antibodies used were MIB-1, nm23, Bcl-2, MMP-9, EMMPRIN (CD147) and alpha-catenin. Scoring employed a grading system (0/1/2/3), and was performed by two pathologists independently. The tissues revealed no significant staining differences for MIB-1, Bcl-2, MMP-9 or EMMPRIN, and therefore no linkage to metastatic potential was determined. Alpha-Catenin showed a diminished level of expression in cases of metastatic mesothelioma (P = 0.024), possibly reflecting dimished catenin-cadherin binding and paralleling data from other tumours. nm23 showed greater staining in metastatic tumours when compared with the controls (P = 0.001). Intriguingly, the nm23 staining pattern was the reverse of that expected. This reversed pattern has been noted before in other tumours and therefore a biological prognostic event may exist for this antibody test and mesothelioma metastasis. CONCLUSION: There may be a place for nm23 and possibly alpha-catenin in immunohistochemical assessment of mesothelioma metastatic potential. However, MIB-1, Bcl-2, MMP-9 and EMMPRIN (CD147) do not show significant staining results.

Effect of treatment of chronic periodontitis on levels of serum markers of acute-phase inflammatory and vascular responses.

AIMS: Recent epidemiological work suggests an association between periodontal disease severity and cardiovascular disease risk. This study aimed to ascertain if circulating levels of cardiovascular and systemic inflammatory markers could be modified following treatment of periodontal disease. METHOD: Adult subjects were recruited from those awaiting periodontal treatment and randomised to either immediate (test, n=24) or delayed treatment (control, n=15). Demographic and clinical data were collected and venous blood was taken before and either 6 weeks after completion of treatment or after an equivalent 3-month control period. Periodontal examination included probing depth, loss of attachment, plaque scores and bleeding scores. Blood was analysed to determine serum and plasma fibrinogen, C-reactive protein, sialic acid, tumour necrosis factor-alpha and interleukin -6 and -1beta. Effects of treatment were assessed by paired tests and analysis of variance by treatment group with baseline covariates. RESULTS: Treatment improved plaque and bleeding scores and reduced probing depths (p<0.002). However, there were no statistically significant changes in levels of any of the systemic markers. CONCLUSION: Improvement in periodontal health did not influence the levels of vascular markers.

Serum sialic acid, a reputed cardiovascular risk factor, is related to serum leptin concentrations in Fijians.

BACKGROUND: Serum sialic acid (TSA) has been shown to be a cardiovascular risk factor and an acute phase reactant, with elevated concentrations associated with increased cardiovascular mortality and to precede the onset of type 2 diabetes. AIM: The purpose of this present study was to test the hypothesis that serum TSA may be related to serum leptin concentrations in healthy individuals. METHODS: Thirty Fijian individuals were studied (8 males and 22 females). They were urban Melanesians living in Raiwaga, a suburb of Suva in Fiji. RESULTS: Serum TSA significantly correlated with subject body mass index (BMI, rho 0.39, P<0.05) and serum leptin concentration (rho 0.44, P<0.05). In stepwise multiple regression analysis serum TSA independently correlated with subject waist/hip ratio (r(2)=0.167, P<0.02) and diastolic blood pressure (r(2)=0.300, P<0.01) but not with age, BMI, serum insulin-like growth factor binding protein (IGFBP-1), fasting plasma glucose or systolic or diastolic blood pressure. CONCLUSIONS: Serum TSA is related to markers of obesity and adipose tissue metabolism which may help to explain why it is a reputed cardiovascular risk factor and why elevated serum TSA concentrations precede the development of type 2 diabetes mellitus.

Measurement of urine total sialic acid: comparison of an automated ultraviolet enzymatic method with a colorimetric assay.

An automated ultraviolet (UV) enzymatic assay for urine total sialic acid (SA), performed on a Cobas Fara analyser, is described and compared with the colorimetric Warren method, which is used widely to determine urine SA. Intra-assay coefficient of variation (CV) for urine total SA determination was 0.83% for the UV assay and 3.5% for the Warren method. Inter-assay CVs were 1.8% and 5.6%, respectively. Recovery of urine total SA ranged from 89% for the UV assay to 61% for the Warren method. Both were linear over a range of urine SA from 20 to 240 mg/L The UV assay was automated, took approximately 20 min to produce a result and avoided the need for solvent extraction; however, the reagents were expensive in comparison to those required for the Warren method. Urine samples with a creatinine concentration > 14 mmol/L were diluted with distilled water to optimise SA recovery by the UV method. Urine SA:creatinine ratios for normals were 4.7 (+/- 1.7) g/mol with the Warren method and 4.5 (+/- 1.0) g/mol for the UV method. Similarly, in type-2 diabetic patients, urine SA:creatinine ratios were 7.6 (+/- 2.3) g/mol (P<0.001) and 8.5 (+/- 2.9) g/mol (P<0.001), respectively.

Offline telepathology diagnosis of colorectal polyps: a study of interobserver agreement and comparison with glass slide diagnoses.

BACKGROUND/AIMS: Technological advances have produced telepathology systems with high quality colour images and reasonable transmission times. Most applications of telepathology have centred on the remote diagnosis of frozen sections or remote real time expert opinions. This study investigates the reproducibility and accuracy of offline telepathology as a primary diagnostic medium for routine histopathology specimens. METHODS: One hundred colorectal polyps (50 hyperplastic, 50 adenomatous) were presented in a randomised order to five histopathologists as offline images on a telepathology workstation. Six images of each case were used: the slide label, a low power scan of all material on the slide, and four higher magnification views. The times taken to prepare the images, and to make the diagnoses, were recorded. Interobserver agreement was measured with kappa statistics and compared with the glass slide diagnoses. RESULTS: The kappa statistics for the interobserver agreement on the telepathology images lay in the range of 0.90-1.00, which is interpreted as excellent agreement, and were significantly higher than those for the glass slide diagnoses (range, 0.84-0.98; p = 0.001). The median time taken to capture the images for a case was 210 seconds. The median time taken to make a diagnosis from the telepathology images was five seconds, which was significantly shorter than for the glass slide diagnoses (median, 13 seconds; p < 0.0005). CONCLUSIONS: Offline telepathology has the potential to be a primary diagnostic medium for routine histopathology with a high degree of reproducibility and short diagnosis times. Further studies are required to validate offline telepathology for different types of specimens and different operators of the image capture system.

Serum sialic acid, a possible cardiovascular risk factor is not increased in Fijian Melanesians with impaired glucose tolerance or impaired fasting glucose.

BACKGROUND: Serum total sialic acid (TSA) has been shown to be a strong cardiovascular risk factor with increased concentrations being associated with increased mortality. Serum TSA is also elevated in patients with type 2 diabetes including those with micro- and macrovascular complications. We wished, therefore, to test the hypothesis that serum TSA may be abnormal in individuals with impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), in Fijian Melanesians. METHOD: Twenty-one subjects with IGT (17 women and four men) were recruited along with 20 subjects with IFG (14 women and six men) and 22 normal subjects (12 women and 10 men). Serum TSA was 2.18 +/- 0.027 mmol//L, 2.19 +/- 0.033 mmol/L and 2.24 +/- 0-042 mmol/L in the three groups, respectively, which was not statistically different. Both systolic and diastolic blood pressure were, however, higher in the IGT group compared with the IFG and normal groups (P<0.04). CONCLUSION: Serum TSA is not elevated in Fijian Melanesians with IGT and IFG although it is reported to be elevated in type 2 diabetes mellitus in other populations. Further research is needed to establish why serum TSA is a potent independent cardiovascular risk factor and is elevated in type 2 diabetes mellitus in some populations.

Serum lipoprotein (A) and apolipoproteins during pregnancy and postpartum in normal women.

This study was designed to investigate whether serum lipoprotein (a) is affected by pregnancy and to relate this to changes in other lipids, lipoproteins and apolipoproteins. The study involved twenty-nine healthy Caucasian pregnant women at term and 27 non-pregnant women matched for age who acted as controls. Samples of venous blood were obtained from 29 pregnant women at term (between 37 and 42 weeks) and 22 of these women provided a second sample after 12 weeks post-partum. Twenty-seven non-pregnant women acted as controls. Samples were taken for Lp(a) and also cholesterol, triglyceride, HDL-cholesterol, apolipoprotein (apo) A and B1. No significant difference was found in the serum concentrations of Lp(a). However, the pregnant women had significantly higher serum concentrations of cholesterol, triglyceride, apo A1 and B (P<0.001) than the controls. The ratio of apo A1: apo B was significantly lower than controls (P<0.001). HDL-cholesterol was not altered by pregnancy but was lower (P<0.05) than the controls after a period of 12 weeks post-partum. Despite a hyperlipidaemia in pregnancy the serum concentrations of Lp(a) are not affected suggesting different metabolic control for this lipoprotein.

The response of serum sialic acid and other acute phase reactants to an oral fat load in healthy humans.

BACKGROUND: Elevated serum total sialic acid (TSA) has been shown to be associated with increased cardiovascular mortality. It has been postulated that atherogenesis is a postprandial phenomenon. We tested the hypothesis that serum TSA and other acute phase proteins, namely C-reactive protein (CRP) and fibrinogen, may be related to the postprandial state. METHODS: Ten healthy male subjects, aged 24-48 years, were fed 62.5 g of total fat (saturates 12 g, monounsaturates 35.3 g and polyunsaturates 12.5 g) in the form of strawberry flavoured Calogen. Venous blood was sampled hourly for 5 h. Concentrations of serum triglyceride, TSA and acute phase proteins were measured. RESULTS: Serum triglyceride concentration increased postprandially, peaking at 240 min. Serum CRP and plasma fibrinogen did not significantly increase after the oral fat load. However, serum TSA did increase from baseline (0.599+/-0.051 g/l) in response to the oral fat load, peaking at 120 min post-oral fat load (0.633+/-0.066 g/l, P<0.02). There was a significant correlation between serum TSA and plasma fibrinogen at baseline (rho=0.62, P=0.05) but not for serum CRP (rho=-0.22) or triglyceride (rho=0.21). CONCLUSIONS: We conclude that serum TSA increases postprandially and this finding gives further insight as to why the former is considered to be a cardiovascular risk factor.