Successful outcome of pregnancy in a patient with familial hypertriglyceridaemia.
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Biomedical subjects
Publications and source records attributed to M Crook.
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The many similarities between arrested dauer larvae of free-living nematodes and infective L3 of parasitic nematodes has led to suggestions that they are analogous lifecycle stages. The control of the formation of dauer larvae in Caenorhabditis elegans is well understood, with a TGF-beta-superfamily growth factor playing a central role. Recent analyses of the expression of homologous TGF-beta genes in parasitic nematodes has allowed this analogy to be tested; but the results so far do not support it. Rather, the results imply that in the evolution of animal parasitism, parasitic nematodes have taken signalling pathways and molecules from their free-living ancestors and used them in different ways in the evolution of their parasitic lifestyles.
Strongyloides ratti is a parasitic nematode of rats. The host immune response against S. ratti affects the development of its free-living generation, favouring the development of free-living adult males and females at the expense of directly developing, infective 3rd-stage larvae. However, how the host immune response brings about these developmental effects is not clear. To begin to investigate this, we have determined the effect of non-immune stresses on the development of S. ratti. These non-immune stresses were subcurative doses of the anthelmintic drugs Ivermectin, Dithiazanine iodide and Thiabendazole, and infection of a non-natural host, the mouse. These treatments produced the opposite developmental outcome to that of the host immune response. Thus, in infections treated with subcurative doses of Ivermectin, Dithiazanine iodide and in infections of a non-natural host, the sex ratio of developing larvae became more female-biased and the proportion of female larvae that developed into free-living adult females decreased. This suggests that the mechanism by which the host immune response and these non-immune stresses affect S. ratti development differs.
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.
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A few years ago a hypothesis was proposed suggesting that elements of the innate immune system, such as acute phase reactants, contribute to the development of Type 2 diabetes mellitus. Acute phase reactants such as C-reactive protein and sialic acid may thus predict risk of developing Type 2 diabetes mellitus, as well as being markers of diabetes microvascular and macrovascular complications. This article discusses these issues.
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.
With the ever increasing demands for pathology testing within the National Health Service there is a need to manage the demand for these tests. This review discusses strategies for the demand management of requests made by clinicians in the disciplines of biochemistry, haematology, and microbiology. The various approaches that have been used to manage demand will be described, along with specific clinical strategies for demand management.
This report describes a case of artifactually low glycated haemoglobin (Hb) in a patient with type II diabetes and severe hypertriglyceridaemia. The effect of hypertriglyceridaemia on glycated Hb determination using the Abbott Vision method was investigated in a series of patients with diabetes. The interference of triglycerides in glycated Hb assays was also investigated by two other methods, the Beckman Synchron CX4 delta immunoturbidimetric method, and the Primus affinity chromatography high performance liquid chromatography assay.
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.
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The lipolysis of triglyceride-rich lipoproteins may provide a surface that supports the activation of factor XII (FXII) with subsequent activation of factor VII (FVII). Plasma levels of activated FVII (FVIIa) but not activated FXII (FXIIa) are increased in the post-prandial state when there is a transient increase in triglyceride levels. We compared plasma levels of FXIIa antigen in control subjects (n = 33) and in patients with chronically elevated lipids (primary hyperlipidaemia, n = 49), with FVIIa and markers of thrombin generation. Results are given as median (first and third quartiles). Plasma levels of FXIIa [2.34 (1.68-3.32) ng/ml versus 1.53 (0.93-1.86) ng/ml, P = 0.0002], FVIIa [3.02 (2.15-4.64) ng/ml versus 2.20 (1.66-2.56) ng/ml, P = 0.0004], thrombin-antithrombin complexes [3.08 (2.16-5.54) microg/I versus 2.13 (1.46-2.84) microg/l, P = 0.005] and prothrombin fragment 1 + 2 (Pro F1 + 2) [1.28 (1.08-1.50) nmol/l versus 0.92 (0.65-1.08) nmol/l, P = 0.0001] were increased compared with controls irrespective of the type of hyperlipidaemia. In hyperlipdaemic subjects, levels of Pro F1 + 2 were correlated with FVIIa (r = 0.56, P = 0.0002) and FXIIa (r = 0.31, P = 0.03). These results suggest increased activation of both FVII and FXII in hyperlipidaemic subjects, which correlates with increased thrombin generation. Given the lack of correlation between levels of FXIIa and FVIIa, it remains to be established whether the increase in FXIIa is responsible for increased FVIIa activity in this subject group.
OBJECTIVES: To compare cardiac troponin T, myoglobin, CK, CKMB activity, CKMB mass and the initial electrocardiogram in the early diagnosis of myocardial infarction in the emergency department. Methods-Biochemical markers were measured at presentation in patients with a possible diagnosis of acute myocardial infarction. Based on the clinical notes, patients were grouped as "definite myocardial infarction" (n = 50), "definite no myocardial infarction" (n = 81) and "uncertain" (n = 96). Sensitivity and specificity and positive and negative predictive values were calculated using the 131 patients with definitely present or absent myocardial infarction. RESULTS: The initial electrocardiogram was more sensitive than any of the markers in the first six hours from symptom onset-sensitivity 74% (95%CI 61% to 88%). The positive predictive value of the initial electrocardiogram was 97% in the first six hours; the markers ranged from 47% to 67%. The negative predictive value of the initial electrocardiogram was 85% in the first six hours; the markers ranged from 61% to 70%. Four patients with non-diagnostic electrocardiograms presenting beyond six hours after pain onset had a myocardial infarct detected by at least three of the biochemical markers in each case. CONCLUSIONS: The electrocardiogram is of more diagnostic use than biochemical markers in the first six hours after the onset of pain, but biochemical markers give additional positive diagnostic information in patients presenting later than this. The negative predictive accuracy of biochemical markers is too low for a single sample to be useful for excluding myocardial infarction in the first six hours after onset of symptoms.
Apolipoprotein H (apo H), also known as beta2-glycoprotein 1, has recently become of interest in the field of haemostasis. As apo H is elevated in diabetes mellitus and dyslipidaemia, we wished to test the hypothesis that serum apo H concentration was related to fasting plasma glucose and insulin as well as blood pressure, body mass index, hip/waist ratio and serum lipids in normal individuals. Eighty-one healthy young individuals (46 females and 35 males) were studied. Their age was 20.7 +/- 0.75 years. Serum apo H significantly correlated with fasting plasma glucose (r = 0.24, P = 0.03) and serum LDL cholesterol (r = 0.30, P = 0.006). In the females serum apo H significantly correlated with serum cholesterol concentration (r = 0.30, P = 0.04) and in males with serum HDL cholesterol concentration (r = 0.35, P = 0.04). In multifactorial regression analysis for serum apo H and the other variables for the 81 subjects, only gender and fasting plasma glucose remained statistically significant in the model. Serum apo H concentrations would be expected to increase by 21.7 mg/L for each single mmol/L increase in fasting plasma glucose (95% CI 2.3-41 2), P = 0.029, and to increase by 17.0 mg/L if the gender is male (95% Cl 0.7-332), P= 0.041.
It is well established that serum total sialic acid (TSA) is elevated in patients with type-2 diabetes mellitus (NIDDM) compared to non-diabetics. However, it is not clear whether serum TSA is also elevated in type-1 diabetic patients (IDDM). Twenty-one type-1 patients were studied along with age and sex matched normal non-diabetic subjects (ten males and 11 females). Their ages were 24.8+/-3.4 years (20-30) and 23.5+/-3.9 years (18-30) respectively. The duration of diabetes mellitus was 12.6+/-6.7 years (1-24) with a HBA1c of 9.0+/-2.2% (6.0-14.9). There was no significant difference in serum TSA of the type-1 diabetic patients 689+/-107 mg/l versus 670+/-119 mg/l in the normal subjects. Nor was there a significant correlation between serum TSA with patient age (r = -0.31), urine albumin/creatinine ratio (ACR) (r = 0.25), HBA1c (r = 0.36), plasma random glucose (r = -0.04) or diabetes duration (r = -0.09) in the diabetic patients. However, there was a significant correlation between serum TSA and mean daily insulin dose (r = 0.51, P<0.02) and also serum cholesterol and triglyceride (r = 0.58, P<0.01 and r = 0.49, P<0.04, respectively) in the type-1 diabetic patients. In summary, we conclude that serum TSA is not elevated in young type-1 diabetic patients compared with normal age and sex matched control subjects. However, the relationship between serum TSA and serum lipids and also mean daily insulin dose merits further research.
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