Association between triglyceride and high-density lipoprotein cholesterol change following fibrate therapy.

BACKGROUND: Debate surrounding the role of fibrates has followed mixed outcomes from several randomised controlled trials. Subgroup analysis of even the negative trials reveals significant reduction in cardiovascular risk amongst patients with low HDL-C and high TG. We previously described factors associated with HDL-C change following fibrates. As fibrates influence both HDL-C and TG levels via their action on PPAR-α, we now wished to study TG change following fibrate therapy and any associations with baseline and change in HDL-C and TC levels. METHODS: Data was collected from case notes of patients started on fibrates (n=248) between 2002 and 2008 in the lipid clinics at Heart of England NHS Foundation Trust. Regression analyses were carried out to determine factors associated with changes in TG. RESULTS: Multiple regression analysis revealed that TG change was associated with pre-treatment TG (p<0.001) and TC levels (p=0.029). The association between TG change and pre-treatment TG remained significant when all factors including gender, concurrent statin treatment, diabetes and baseline HDL-C were entered into the regression model. Our previous study demonstrated significant post-fibrate HDL-C change in the group with baseline HDL-C values <1.0mmol/l. In our present study significant TG reduction was observed regardless of the baseline patient characteristics including HDL-C levels. CONCLUSIONS: The actions of fibrates are considered to be mediated via PPAR-α, but our data suggest that the effects on TG and HDL-C are different. Thus, the mechanisms mediating the changes of these lipids following fibrate treatment may vary.

The prevalence of vitamin D abnormalities in South Asians with type 2 diabetes mellitus in the UK.

BACKGROUND: The high prevalence of both hypovitaminosis D and type 2 diabetes (T2DM) in the Asian community is well recognised, but the impact of diabetes on vitamin D status and vice versa, has not been well reported. AIMS: To determine the prevalence of hypovitaminosis D in Asian patients with T2DM and its impact on glycaemic control. METHODS: A cross-sectional study was conducted in a tertiary referral centre in the UK. Two hundred and ten Asian patients aged more than 40 years were included (170 with and 40 without T2DM). Each had a standard bone profile (serum calcium, phosphate and alkaline phosphatase), serum parathyroid hormone and 25-hydroxycholecalciferol. RESULTS: The prevalence of low serum 25-hydroxyvitamin D (< 50 nmol/l) was high in the group as a whole (> 80%) and more common in diabetics compared with controls (83% vs. 70%; p = 0.07). This was particularly so in men (82.5% vs. 57.9%; p = 0.02). HbA1c was higher in women with vitamin D deficiency (< 12.5 nmol/l) (8.11 +/- 1.11% vs. 7.33 +/- 1.32%, p = 0.046). In logistic regression analysis, T2DM was an independent predictor of hypovitaminosis D. In linear regression analysis, vitamin D deficiency was independently related to HbA1c in women with T2DM. CONCLUSIONS: Hypovitaminosis D remains a major public health issue in the Asian population and is exaggerated in patients with T2DM. The fact that vitamin D deficient women had higher HbA1c levels raises the possibility that vitamin D replacement may improve glycaemic control.

Detection of impaired glucose tolerance and undiagnosed type 2 diabetes in UK South Asians: an effective screening strategy.

AIM: We tested a stepwise, community-based screening strategy for glucose intolerance in South Asians using a health questionnaire in conjunction with body mass index (BMI). Anthropometric measurements (waist and hip circumference, sagittal diameter and percentage body fat) were then conducted in a hospital setting followed by an oral glucose tolerance test (OGTT) to identify subjects at the highest risk and analyse the factors predicting that risk. METHODS: A health questionnaire was administered to 435 subjects in a community setting and BMI was measured. Subjects were graded by a risk score based on the health questionnaire as high, medium and low. Subjects with high and medium risk scores and a representative sample of those with low scores had anthropometric measurements in hospital followed by an OGTT. In total, 205 (47%) of the subjects had an OGTT performed. RESULTS: In total, 48.7% of the subjects tested with an OGTT had evidence of glucose dysregulation: 20% had diabetes and 28.7% had impaired glucose tolerance (IGT). Logistic regression model explained 49.1% of the total variability. The significant predictors of diabetes and IGT were Blood Glucose Monitoring Strips (BMI), random blood glucose (BM), sibling with diabetes and presence of diagnosed hypertension or ischaemic disease. Most of these predictors along with other heredity diabetes factors create a composite score, with high predictability, as the receiver operating curve analysis shows. CONCLUSION: We describe a simple, stepwise strategy in a community setting, based on a health questionnaire and anthropometric measurements, to explain about 50% of cases with IGT and diabetes and diagnose about 50% of cases from the population screened. We have also identified factors that predict the risk.

Central pontine myelinolysis following 'optimal' rate of correction of hyponatraemia with a good clinical outcome.

Central pontine myelinolyis (CPM), an acute demyelinating condition of the brain stem, is a recognized complication of the treatment of patients with chronic hyponatraemia (hyponatraemia >48 h), particularly in those who abuse alcohol. The risk of CPM is believed to be associated with a rapid (>8 mmol/L/day) correction of the serum sodium concentration, which is said to lead to an osmotically-induced demyelination. CPM is also commonly believed to have a poor, and often fatal, outcome. We report the case of a 37-year-old female alcoholic patient who presented following a collapse, and who was hyponatraemic (serum sodium concentration 105 mmol/L). The rate at which the serum sodium concentration was corrected to normal was less than the 8 mmol/L/day guideline, but nonetheless she developed the clinical and radiological features of CPM. She made a good neurological recovery, however, and was able to be discharged from hospital. CPM does not necessarily have a bleak prognosis, and may occur even with optimal rates of correction of the serum sodium concentration. Clinicians should recognize that the outcome of CPM is not inevitably poor, and the complication may occur despite appropriate management. It is possible that CPM is a complication of the hyponatraemia itself, rather than the treatment of the biochemical disturbance.

Serum resistin is associated with C-reactive protein & LDL cholesterol in type 2 diabetes and coronary artery disease in a Saudi population.

AIMS: Resistin is an adipocyte-derived factor implicated in obesity-associated type 2 diabetes (T2DM). This study examines the association between human serum resistin, T2DM and coronary heart disease. METHODS: One hundred and fourteen Saudi Arabian patients (male: female ratio 46:68; age 51.4 (mean +/- SD)11.7 years; median and range: 45.59 (11.7) years and BMI: 27.1 (mean +/- SD) 8.1 Kgm2 median and range: 30.3 (6.3) were studied. Serum resistin and C-reactive protein (CRP), a marker of inflammation CRP levels, were measured in all subjects. (35 patients had type 2 diabetes mellitus (T2DM); 22 patients had coronary heart disease (CHD). RESULTS: Serum resistin levels were 1.2-fold higher in type 2 diabetes and 1.3-fold higher in CHD than in controls (p = 0.01). In addition, CRP was significantly increased in both T2DM and CHD patients (p = 0.007 and p = 0.002 respectively). The use of regression analysis also determined that serum resistin correlated with CRP levels (p = 0.04, R2 0.045). CONCLUSION: The findings from this study further implicate resistin as a circulating protein associated with T2DM and CHD. In addition this study also demonstrates an association between resistin and CRP, a marker of inflammation in type 2 diabetic patients.

Characteristics of Type 1 diabetes of over 50 years duration (the Golden Years Cohort).

BACKGROUND: Type 1 diabetes mellitus is associated with high levels of premature morbidity and mortality. Prolonged survival is possible, however, and some patients appear to be protected from the long-term complications of this condition. METHODS: Diabetes UK awards medals to patients who have had Type 1 diabetes for 50 years or more. By examining medal-holders, we have established the clinical and biochemical features of a group of 400 subjects (54% male) with Type 1 diabetes of long duration. RESULTS: Mean age of the subjects was 68.9 years and mean age-at-onset of diabetes 13.7 years. Features of long duration diabetes in this cohort include normal body mass (mean BMI 25.0 kg m-2), low insulin dose (mean 0.52 units kg-2) and greatly elevated HDL-cholesterol (mean 1.84 mmol/l). Mean HbA1c was 7.6% (normal range 3.8-5.0%) and no patient had a normal HbA1c at the time of venesection. As a group, they have long-lived parents and consume moderate amounts of alcohol. Medical contact has often been sporadic. A significant proportion (29%) were taking anti-hypertensive medication. Screening for micro- and macroalbuminuria was positive in 35.7%. CONCLUSIONS: Patients with long-duration (> 50 years) Type 1 diabetes are relatively protected from clinical diabetic nephropathy and large vessel disease; our data are consistent with protection possibly being genetically determined in part via elevated HDL-cholesterol levels. An abnormal urinary albumin/creatinine ratio is common in these patients, despite their low risk of significant renal deterioration; this may have implications for microalbuminuria screening programmes.

Serum leptin is elevated in Saudi Arabian patients with metabolic syndrome and coronary artery disease.

AIMS: To compare plasma leptin in Saudi subjects with Type 2 diabetes and coronary heart disease (CHD) with non-diabetic control subjects and to examine the relationship of plasma leptin to other CHD risk factors. RESEARCH DESIGN AND METHOD: Serum leptin concentrations were measured in 144 Saudi men. Subjects studied included 59 with Type 2 diabetes mellitus [BMI 27.5 (3.7) kg/m2 mean (sd)], 34 with coronary heart disease [BMI 29.6 (1.8) kg/m2], and 51 non-diabetic controls [BMI 28.0 (3.5) kg/m2]. There was no significant difference in BMI between the groups. Fasting serum leptin, lipids, insulin, apolipoproteins and glucose were measured. BMI, blood pressure; smoking habit and age were also recorded. Insulin resistance was assessed using the HOMA model. RESULTS: Leptin concentrations were significantly higher in diabetic and CHD patients than in controls (P = 0.024 and 0.016, respectively). Multiple regression analysis showed that body weight (P < 0.0006), serum triglyceride concentration (P = 0.046) and systolic blood pressure (P = 0.013) were all significantly related to the logarithm of the serum leptin concentration (R2 = 0.549) in CHD patients. A subgroup analysis, comparing those patients who had the metabolic syndrome, as defined by WHO, with controls, showed higher serum leptin in those with metabolic syndrome (P = 0.05). CONCLUSIONS: Serum leptin is increased in Saudi subjects with diabetes mellitus, metabolic syndrome and CHD. Leptin may be a marker of risk of CHD, at least in men, and contribute to the CHD risk profile in subjects with insulin resistance. Further studies are needed to evaluate this relationship prospectively.

Cardiovascular risk assessment in patients with retinal vein occlusion.

AIM: Patients with retinal vein occlusions (RVO) are at increased risk of cardiovascular disease (CVD). The risk of future CVD was determined using the Framingham algorithm and this risk estimate was used to guide decisions about preventative treatment for CVD in RVO patients. METHODS: 107 unselected RVO patients were studied. After excluding 18 patients because of age, missing data, or pre-existing cardiovascular disease, the calculated coronary heart disease risks (cCHDR) and calculated cardiovascular disease risks (cCVDR) were calculated on the 89 remaining and compared with both the standardised risk and the published incidence of CHD in England by t test or chi(2) test. RESULTS: The mean 10 year cCVDR was significantly higher than the Framingham standardised risk for all RVOs (20.6% (1.2%) v 15.7% (1.1%), p = 0.009) and female RVOs (17.8% (1.2%) v 12.7% (1.0%), p = 0.022) in particular. The 10 year cCHDR, compared to the actual incidence of CHD in England between the ages of 30 and 74 years, was > 15% in twice as many males than expected (62% v 28%, p <0.0001). This rose to almost six times when cCHDRs greater than 30% were compared (17% v 3%, p = 0.002). There was a fourfold increase in the proportion of female RVO patients with a cCHDR above 15% (40% v 9%, p <0.0001) and at a cCHDR of 30% and above (10% v 0%, p = 0.004). There were also significant differences in the cCHDR between central and branch RVO (both sexes). The branch form of RVO (BRVO) having higher cCHDRs because of systolic hypertension (164.1 (21.6) mm Hg v 149.5 (23.5) mm Hg, p = 0.003) and age (61.7 (8.3) years v 56.7 (10.6) years, p = 0.017). CONCLUSIONS: RVO is the presenting complaint in a group of patients at increased risk of CVD and is in agreement with the long term follow up data demonstrating an increased mortality from CVD in patients with RVO. The Framingham algorithm can accurately determine the cCHDR (or cCVDR) to assist the clinician in deciding who to treat in accordance with the Joint British Societies' guidelines, with particular regard to hypertension, lipid lowering, and the use of aspirin therapy.

Serum homocysteine concentration is related to diabetes mellitus, but not to coronary heart disease, in Saudi Arabians.

INTRODUCTION: Plasma homocysteine (HCYS) concentration is believed to be an independent risk factor for atherosclerosis. METHODS: HCYS was measured in a cohort of 584 Saudi Arabians participating in a national screening study of coronary heart disease (CHD) risk factors. A total of 173 subjects (114 men and 59 women) had clinical CHD, of whom 82 (47.4%) had type 2 diabetes mellitus (56 men and 26 women). A further 127 subjects (60 men and 67 women) also had type 2 diabetes mellitus but no CHD. A total of 284 individuals (120 men and 164 women) were recruited as healthy controls, and had no previous history of CHD or diabetes. Serum HCYS was measured by high-performance liquid chromatography (HPLC) with electrochemical detection. RESULTS: Univariate analysis showed HCYS concentrations were significantly lower in those with diabetes mellitus (DM) than in controls, for both men [8.7 (4.2-18.6) vs. 10.5 (4.5-20.5) mmol/l, median (5th-95th percentiles, p = 0.009] and women [6.3 (3.3-24.0) vs. 8.1 (4.0-17.9) mmol/l, p = 0.049]. Stepwise multivariate regression analysis indicated a relationship between HCYS concentration and age, sex and the presence of DM, but not with CHD. CONCLUSIONS: In the Saudi Arabian population, serum HCYS is not a risk factor for CHD, but is lower in patients with DM.

Permeabilization of model lipid membranes by Bacillus sphaericus mosquitocidal binary toxin and its individual components.

The high larvicidal effect of Bacillus sphaericus (Bs), a mosquito control agent, originates from the presence of a binary toxin (Bs Bin) composed of two proteins (BinA and BinB) that work together to lyse gut cells of susceptible larvae. We demonstrate for the first time that the binary toxin and its individual components permeabilize receptor-free large unilamellar phospholipid vesicles (LUVs) and planar lipid bilayers (PLBs) by a mechanism of pore formation. Calcein-release experiments showed that LUV permeabilization was optimally achieved at alkaline pH and in the presence of acidic lipids. BinA was more efficient than BinB, BinB facilitated the BinA effect, and their stoichiometric mixture was more effective than the full Bin toxin. In PLBs, BinA formed voltage-dependent channels of approximately 100-200 pS with long open times and a high open probability. Larger channels (> or =400 pS) were also observed. BinB, which inserted less easily, formed smaller channels (< or =100 pS) with shorter mean open times. Channels observed after sequential addition of the two components, or formed by their 1:1 mixture (w/w), displayed BinA-like activity. Bs Bin toxin was less efficient at forming channels than the BinA/BinB mixture, with channels displaying the BinA channel behavior. Our data support the concept of BinA being principally responsible for pore formation in lipid membranes with BinB, the binding component of the toxin, playing a role in promoting channel activity.

Comparative accuracy of cardiovascular risk prediction methods in patients with diabetes mellitus.

OBJECTIVE: To compare the accuracy of cardiovascular risk prediction methods based on equations derived from the Framingham Heart Study in a cohort of patients with diabetes mellitus. RESEARCH DESIGN AND METHODS: Risk factor data was collected prospectively from 906 patients with diabetes mellitus. Absolute cardiovascular risks were calculated using the Framingham equation, and estimated with the currently available Framingham-based risk tables and charts. The sensitivity, specificity, positive and negative predictive values of the tables and charts to assess cardiovascular risk were assessed using calculation of risk from the full Framingham equation as the reference method. RESULTS: In all, 146 subjects (16.1%) had calculated 10-year coronary heart disease (CHD) risks > or = 30%, and 585 (64.6%) had risks > or = 15%. For identification of those at 10-year CHD risk > or = 30%, the original Sheffield tables had a sensitivity of 43% (95% confidence intervals (CI) 19.9-61.7%) and specificity of 94% (CI 90.8-96.7%). Modifications of the Sheffield tables improve sensitivity (95% CI 93.9-97%) but reduce specificity (90% CI 85.6-95.7%). The Joint British Guidelines' charts have a moderate sensitivity (69.5% CI 51.8-81.9%) and high specificity (99.7% CI 98.9-100%). For identification of individuals at a 10-year CHD risk > or = 27%, the Framingham categorical tables had a sensitivity of 95% (CI 91.6-97.8%), but a specificity of only 83% (95% CI 79.1-85.5%). CONCLUSIONS: The Joint British charts appear to have the best performance in a cohort of patients with diabetes mellitus, however, calculation of CHD/CVD (cardiovascular disease) risks with personal or laboratory computers using the full Framingham equation remains the most accurate way to assess cardiovascular risk in a primary prevention setting.

A pilot study of homocyst(e)ine levels in essential hypertension: relationship to von Willebrand factor, an index of endothelial damage.

An interaction between homocyst(e)ine and the endothelium in hypertensive patients may promote thrombogenesis and atherogenesis, leading to adverse cardiovascular events. We hypothesized that homocyst(e)ine levels are abnormal in patients with essential hypertension, and that this may be related to an adverse effect on the vascular endothelium. Accordingly, we compared plasma levels of homocyst(e)ine and von Willebrand factor (marking endothelial damage) in 83 patients (43 men; mean age 54 +/- standard deviation 15.9 years) with essential hypertension (> 160/90 mm Hg), with levels in 25 healthy normotensive controls (13 men; mean age 56+/-11.8 years). Baseline levels of the markers and other clinical indices were then related to adverse cardiovascular events at follow-up. Plasma homocyst(e)ine (P = .0001) and von Willebrand factor (P = .031) levels were significantly higher in hypertensives compared to controls. After a mean follow-up of 76 patients for 45 months (range, 1 to 66 months), 17 subjects experienced an end point of either cardiovascular death (n = 10) or adverse cardiovascular event (n = 7). Comparing these 17 with the 59 free of an end point, the former were older (P = .0002) and had a longer duration of known hypertension (P = .018). There was a nonsignificant trend toward higher median plasma homocyst(e)ine levels in the patients sustaining a vascular end point (P = .07). In this pilot study, we suggest that essential hypertension may be associated with increased plasma homocyst(e)ine levels, but that this amino acid is unrelated to endothelial damage (von Willebrand factor), clinical indices, or prognosis.

Coronary heart disease risk assessment in diabetes mellitus--a comparison of PROCAM and Framingham risk assessment functions.

AIMS: To assess any differences between coronary heart disease (CHD) risks calculated by the Framingham equation and those calculated by the PROCAM equation in men with and without diabetes mellitus, and whether any such differences are associated with the hypertriglyceridaemia of diabetes mellitus. METHODS: Clinical and biochemical data collected from 1774 men seen in either general practice, a hospital diabetes or lipid clinic. CHD risks were calculated by both the Framingham and PROCAM functions and comparisons made between those patients with and those without diabetes. RESULTS: Of the 1774 men only 996 fulfilled the criteria for assessment by the PROCAM equation and thus further analysis. Patients with diabetes mellitus had significantly higher serum triglyceride levels than those without (1.9 mmol/l vs. 1.7 mmol/l). Median annual CHD risks calculated by the Framingham function were 1.7% in the patients with and 1.32% in the patients without diabetes mellitus, whereas those calculated by the PROCAM function were 0.77% and 0.6%, respectively. Bland-Altman difference plots showed that in both groups of patients the PROCAM equation systematically underestimated risk in comparison with the Framingham equation at low levels of risk but overestimated at higher levels of risk. The shape of the plots in each group of patients was, however, similar. CONCLUSION: There were no systematic differences between CHD risks calculated by the two different equations in patients with diabetes compared with those without, despite the higher serum triglyceride levels associated with diabetes. Restrictions in the use of the PROCAM function meant that only 56% of the original cohort could be assessed in this way. Thus the Framingham equation remains the most suitable method of CHD risk prediction for UK patients with and without diabetes mellitus.

A whole-body physiologically based pharmacokinetic model incorporating dispersion concepts: short and long time characteristics.

In whole-body physiologically based pharmacokinetic (PBPK) models, each tissue or organ is frequently portrayed as a single well-mixed compartment with distribution, perfusion rate limited. However, single-pass profiles from isolated organ studies are more adequately described by models which display an intermediate degree of mixing. One such model is the dispersion model, which successfully describes the outflow profiles from the liver and the perfused hindlimb of many compounds, under a variety of conditions. A salient parameter of this model is the dispersion number, a dimensionless term, which characterizes the relative axial spreading of compound on transit through the organ. We have developed a whole-body PBPK model wherein the distribution of drug on transit through each organ is described by the dispersion model with closed boundary conditions incorporated. The model equations were numerically solved using finite differencing methods, in particular, the method of lines. An integrating routine suitable for solving stiff sets of equations was used. Physiological parameters, blood flows, and tissue volumes, were taken from the literature, as were the tissue dispersion numbers, which characterize the mixing properties of each tissue; where none could be found, the value was set as that for liver. On solution, tissue, venous and arterial blood concentration-time profiles are generated. The profiles exhibited both short and long time characteristics. Oscillations were observed in the venous and arterial profiles over the first 10 min of simulation for the rat. On scale-up to human, the effects were seen over a 30 min period. Longer time effects of tissue distribution involve buildup of drug in the large tissues of distribution: skeletal muscle, skin, and adipose. The extent of distribution in the large tissues was somewhat dependent on the magnitude of the dispersion number, the lower the dispersion number, the greater the extent of distribution after an intravenous bolus dose. The model has a distinct advantage over the well-stirred organ whole-body PBPK model in its ability to describe both short and long time characteristics.

Comparative accuracy of cardiovascular risk prediction methods in primary care patients.

OBJECTIVE: To compare the relative accuracy of cardiovascular disease risk prediction methods based on equations derived from the Framingham heart study. DESIGN: Risk factor data were collected prospectively from subjects being evaluated by their primary care physicians for prevention of cardiovascular disease. Projected cardiovascular risks were calculated for each patient with the Framingham equations, and also estimated from the risk tables and charts based on the same equations. SETTING: 12 primary care practices (46 doctors) in Birmingham. PATIENTS: 691 subjects aged 30-70 years. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of the Framingham based risk tables and charts for treatment thresholds based on projected cardiovascular disease or coronary heart disease risk. RESULTS: 59 subjects (8.5%) had projected 10 year coronary heart disease risks >/= 30%, and 291 (42.1%) had risks >/= 15%. At equivalent projected risk levels (10 year coronary heart disease >/= 30% and five year cardiovascular disease >/= 20%), the original Sheffield tables and those from New Zealand have the same sensitivities (40.0%, 95% confidence interval (CI) 26.6% to 57.8% v 41.2%, 95% CI 28.7% to 57. 3%) and specificities (98.6%, 95% CI 97.2% to 99.3% v 99.7%, 95% CI 98.8% to 100%). Modifications to the Sheffield tables improve sensitivity (91.4%, 95% CI 81.3% to 96.9%) but reduce specificity (95.8%, 95% CI 93.9% to 97.3%). The revised joint British recommendations' charts have high specificity (98.7%, 95% CI 97.5% to 99.5%) and good sensitivity (84.7%, 95% CI 71.0% to 93.0%). CONCLUSIONS: The revised joint British recommendations charts appear to have the best combination of sensitivity and specificity for use in primary care patients.

Plasma total homocysteine and retinal vascular disease.

PURPOSE: Hyperhomocysteinaemia has been linked to macrovascular disease. Our aim was to investigate whether there is a relationship between fasting plasma total homocysteine levels and retinal vascular disease. METHODS: We measured the homocysteine levels in 70 patients with arterial or venous retinal vessel occlusion and compared them with the levels in 85 controls without evidence of ischaemic heart disease. Homocysteine levels were determined by high-performance liquid chromatography with electrochemical detection and compared after logarithmic transformation. RESULTS: Homocysteine levels were found by univariate analysis (unpaired two-tailed t-test) to be significantly higher in the group with retinal artery occlusion than the group with retinal vein occlusion (p = 0.045) and in both groups compared with controls (18.4 and 13.8 vs 9.5 mumol/l; p = 0.0002 and < 0.0001, respectively). The controls, however, were significantly younger than the subjects (51.5 +/- 15.4 vs 66.2 +/- 11.9 years; p < 0.0001), but analysis of the results by age revealed significant differences between the groups and controls for the seventh decade (vein occlusions, p = 0.05) and for the eighth decade (artery occlusions, p = 0.037). Subgroup analysis of the retinal vessel occlusion group revealed significant differences in mean blood pressure between those with branch retinal vein occlusions (175/100 mmHg) and both those with central retinal vein occlusions (155/88 mmHg) and those with retinal artery occlusions (157/86 mmHg). Both vein occlusion subgroups also differed significantly with regard to homocysteine levels, branch < central (12.2 +/- 1.3 vs 15.0 +/- 1.6 mumol/l, p = 0.03). Multiple linear regression analysis revealed significant relationships between homocysteine levels and the presence of retinal vessel occlusion (p = 0.0002), serum creatinine (p = 0.001) and age (p = 0.003), but not gender. CONCLUSIONS: We conclude that homocysteine may be a risk factor for retinal vascular disease and could be simply and cheaply treated with folate and vitamins B6 and B12.

A mathematical model of the stress induced during avascular tumour growth.

In this paper a mathematical model is developed to describe the effect of nonuniform growth on the mechanical stress experienced by cells within an avascular tumour. The constitutive law combines the stress-strain relation of linear elasticity with a growth term that is derived by analogy with thermal expansion. To accommodate the continuous nature of the growth process, the law relates the rate of change of the stress tensor to the rate of change of the strain (rather than relating the stress to the strain directly). By studying three model problems which differ in detail, certain characteristic features are identified. First, cells near the tumour boundary, where nutrient levels and cell proliferation rates are high, are under compression. By contrast, cells towards the centre of the tumour, where nutrient levels are low and cell death dominant, are under tension. The implications of these results and possible model developments are also discussed.