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Microvascular Disease (microvascular + disease)
Selected AbstractsThe influence of exercise on foot perfusion in diabetesDIABETIC MEDICINE, Issue 10 2007D. T. Williams Abstract Aims, Diabetic foot disease is associated with both macro- and microvascular disease. Exercise has both positive and negative effects on the perfusion of lower limbs with peripheral arterial occlusive disease (PAOD). We aimed to measure changes in foot perfusion following a brief period of lower-limb exercise in individuals with and without Type 2 diabetes and non-critical PAOD. Methods, Subjects were allocated to groups according to the presence or absence of diabetes, PAOD on colour duplex imaging and clinically detectable peripheral neuropaÍthy. Transcutaneous oxygen tension (TcPO2), transcutaneous carbon dioxide tension (TcPCO2), ankle-brachial pressure indices, toe pressures and toe-brachial pressure indices (TBI) were measured. Results, One hundred and sixteen limbs were studied in 61 subjects. Post-exercise, toe pressure and TBI increased in the non-diabetic group with arterial disease, but not in the groups with diabetes. Foot TcPO2 values increased in groups with diabetes and TcPCO2 decreased in all groups with arterial disease. Increased chest TcPO2 and decreased TcPCO2 were demonstrated in the groups with diabetes. Conclusions, Elevations in foot TcPO2 and reductions in TcPCO2 indicate improved cutaneous perfusion response to local heating post-exercise. Elevated toe pressures in the non-diabetes group suggest that improved perfusion may be associated with enhanced lower limb macrovascular haemodynamics. However, improvements in TcPO2 and TcPCO2 at foot and chest sites in diabetes imply a global change in cutaneous perfusion. The results suggest that brief exercise results in an improvement in cutaneous perfusion in non-critical PAOD, particularly in individuals with diabetes. [source] Insulin treatment and cardiovascular disease; friend or foe?DIABETIC MEDICINE, Issue 2 2005A point of view Abstract Background Several observational studies have shown that higher insulin levels are associated with an increased risk of cardiovascular disease. If higher endogenous insulin levels are causally related to cardiovascular disease, one might expect an increased risk of cardiovascular disease in patients treated with insulin, as this results in high circulating insulin levels. Such risk elevation might counteract the benefits of tight glucose control. Our objective was to explore the relationship between insulin therapy and cardiovascular disease in Type 1 and Type 2 diabetes mellitus using information from available literature. Summary of comment Several experimental studies in animals and humans support the presence of a harmful effect of insulin on the vascular endothelium. In prospective follow-up studies increased insulin dosage was associated with increased risks of cardiovascular disease, although confounding by indication could not be excluded. Randomized controlled trials in diabetic patients, comparing conventional with intensive glucose-lowering treatment, although showing a reduction in microvascular disease, showed no significant difference in the incidence of cardiovascular disease. The results with respect to exposure to insulin are, however, difficult to interpret due to insufficient information on exposure to insulin levels as well as confounding by glycaemic control and body mass index. In addition, these studies were not designed to address the question whether higher insulin use relates to increased cardiovascular risk. Conclusion Published research provides conflicting evidence as to whether exposure to high levels of exogenous insulin in diabetes mellitus affects the risk of cardiovascular disease. The currently available studies have a number of serious methodological restraints that limit accurate interpretation and conclusions in this area. [source] Diabetes control and complications: the role of glycated haemoglobin, 25 years onDIABETIC MEDICINE, Issue 7 2004S. L. Jeffcoate Abstract The long-term complications of diabetes have major consequences for individual subjects and growing healthcare delivery and cost implications for society. Evidence for the benefits of good glycaemic control, as monitored by glycated haemoglobin measurements, has been developed in the 25 years since they were introduced to the point where HbA1c assays play central roles in patient management, clinical guidance and audit, and clinical trial design. In this review this evidence is examined and three classes of uncertainty identified that diminish confidence in the effectiveness of these roles for HbA1c. 1Analytical variability between different methods for HbA1c has restricted the application of clinical targets and this problem has recently been addressed by reference method standardization. There are two approaches to this which result in different HbA1c values and this discrepancy needs to be resolved. 2Biological variability in HbA1c values between individuals also restricts its predictive role when applied to populations. The correlations between HbA1c measurements and various components of glycaemia (overall, fasting, postprandial) are still uncertain and differences in protein glycation and de-glycation are greater between subjects than often thought. The influence of variability in erythrocyte life span is an area where research is needed, especially in diabetic subjects. 3Clinical variability is the most important and complex area of uncertainty. A predictive link between HbA1c and clinical outcomes is not as clear-cut as often stated. The correlation with the development of microvascular disease is well established in Type 1 diabetes, but in Type 2 subjects (90% of those with diabetes) the evidence that HbA1c monitoring is of value in predicting or preventing macrovascular disease is not strong, although it is the major cause of morbidity and early death in this group. It is recommended that, as a matter of urgency, these issues be examined, particularly within the context of self-care in diabetes. Diabet. Med. **, ***,*** (2003) [source] Buccal delivery of insulin: the time is nowDRUG DEVELOPMENT RESEARCH, Issue 7 2006*Article first published online: 16 NOV 200, Gerald Bernstein Abstract The burgeoning numbers of individuals with diabetes mellitus and prediabetes, in particular Type 2 including large numbers of children, open up not only the classic risks for microvascular disease but the earlier and incapacitating risk for macrovascular disease. Oral hypoglycemic agents and insulin sensitizers have not been adequate to control postprandial glucose. Prandial insulin is most desirable but resistance to injections limits its use. This has led to a battery of needle-free insulin delivery systems. Buccal delivery stands out as being safe, simple, fast, flexible, and familiar to patient and physician alike. Drug Dev. Res. 67:597,599, 2006. © 2006 Wiley-Liss, Inc. [source] Neuropathological evidence for ischemia in the white matter of the dorsolateral prefrontal cortex in late-life depressionINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 1 2003Alan J. Thomas Abstract Background Signal hyperintensities on magnetic resonance imaging in late-life depression are associated with treatment resistance and poor outcome. These lesions are probably vascular in origin and proposed sites for vascular damage include the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). Methods We therefore examined white matter in these areas for microvascular disease and evidence of ischemia using intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1). We obtained postmortem tissue from elderly depressed (n,=,20) and control (n,=,20) subjects and blindly rated microvascular disease and ICAM-1 and VCAM-1 amount using quantitative image analysis in sections of the DLPFC, ACC and occipital cortex (OC; control area). Results We found a significant increase in ICAM-1 in the deep white matter of the DLPFC in the depressed group (p,=,0.01) and a trend towards an increase for VCAM-1 (p,=,0.10). In the gyral white matter there was a trend towards significance for both molecules (p,=,0.07 and 0.10). No differences were found in the ACC or OC or for microvascular disease in any area. Conclusions These findings are consistent with white matter ischemia in the DLPFC and lend support to the ,vascular depression' hypothesis. They implicate the DLPFC as an important site in the pathogenesis of late-life depression and have major implications for the understanding and management of late-life depression and raise the possibility of novel treatments being introduced in the future. Copyright © 2002 John Wiley & Sons, Ltd. [source] Pathogenesis and treatment of diabetic vascular disease , illustrated by two casesJOURNAL OF INTERNAL MEDICINE, Issue 5 2006U. SMITH Abstract. This publication is a summary of the presentations given at the First JIM Grand Round held at the Sahlgrenska University Hospital on 15 March 2006. The Grand Round was based on two case reports; a patient with type 2 diabetes and pronounced macrovascular disease and another patient with early microvascular disease combined with the macrovascular complications. The pathogenesis of the vascular complications and the current treatment regimens were discussed in relation to the history and examinations performed in these patients. [source] Methylenetetrahydrofolate reductase and methionine synthase reductase gene polymorphisms and protection from microvascular complications in adolescents with type 1 diabetesPEDIATRIC DIABETES, Issue 4pt2 2008Esko J Wiltshire Abstract:, Folate status has been associated with endothelial dysfunction in adolescents with type 1 diabetes, and elevated total plasma homoocyst(e)ine (tHcy) is a risk for vascular disease in the non-diabetic population. Polymorphisms in genes involved in folate and homocysteine metabolism are implicated in vascular disease. We aimed to determine whether polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes are risk factors for early microvascular disease in a large group of adolescents with type 1 diabetes. Four hundred and eighty adolescents were screened annually for retinopathy and microalbuminuria for a median of 4 yr. Molecular analysis for the polymorphisms 677C,T, 1298A,C in MTHFR, and 66A,G in MTRR was performed. The MTRR 66GG genotype reduced the risk for elevated albumin excretion rate (AER) (OR 0.47, CI 0.25, 0.88, p = 0.018) and showed a trend to reduced risk for microalbuminuria (OR 0.27, CI 0.06,1.21, p = 0.09). Survival without elevated AER was increased with the MTRR 66GG genotype (12.4 vs. 9.7 yr, p = 0.04) and with the MTHFR 1298CC genotype (15.2 vs. 10.2 yr, p = 0.007). Conversely, survival without retinopathy was reduced with the MTHFR 677TT and MTRR 66GG combined genotype (6.2 vs. 10.2 yr, p = 0.015). The MTRR 66GG and MTHFR 1298 CC genotypes may confer protection against early nephropathy, possibly because they are associated with lower tHcy. The MTHFR 677 TT was only related to earlier onset retinopathy in combination with MTRR 66GG. [source] Protein kinase C inhibition in diabetic retinopathy and microvascular diseasePRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 5 2007Dr C Walton FRCP Abstract Protein kinase C (PKC) activation by hyperglycaemia may play an important role in the evolution of diabetic retinopathy and other microvascular complications. The PKC-, inhibitor ruboxistaurin belongs to a new class of drugs and has been studied in several clinical trials in microvascular disease, the outcomes of which are described in this review. Ruboxistaurin exhibits promise as the first oral treatment shown to reduce visual loss and the need for laser treatment for macular oedema in patients with moderate to severe non-proliferative diabetic retinopathy. Copyright © 2007 John Wiley & Sons. [source] Use of fibrates in diabetes: what does the FIELD trial tell us?PRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 3 2006Consultant PhysicianArticle first published online: 24 MAY 200, Dr NI Jowett MD, FRCP Consultant in Cardiovascular Medicine Abstract FIELD was the largest cardiovascular prevention trial using fibrates in type 2 diabetes. Whilst the primary endpoint was not achieved, fenofibrate therapy associated with fewer non-fatal myocardial infarctions and revascularisation procedures. Progress of renal and retinal microvascular disease appeared to be slowed. Although many patients were also taking statin therapy, FIELD does not provide evidence on efficacy or long-term safety when co-prescribed with fibrates. Statin monotherapy remains first line therapy for diabetic dyslipidaemia. Copyright © 2006 John Wiley & Sons, Ltd. [source] Lacunar stroke is associated with diffuse blood,brain barrier dysfunction,ANNALS OF NEUROLOGY, Issue 2 2009FMedSci, Joanna M. Wardlaw MD Objective Lacunar stroke is common (25% of ischemic strokes) and mostly because of an intrinsic cerebral microvascular disease of unknown cause. Although considered primarily to be an ischemic process, the vessel and tissue damage could also be explained by dysfunctional endothelium or blood,brain barrier (BBB) leak, not just ischemia. We tested for subtle generalized BBB leakiness in patients with lacunar stroke and control patients with cortical ischemic stroke. Methods We recruited patients with lacunar and mild cortical stroke. We assessed BBB leak in gray matter, white matter, and cerebrospinal fluid, at least 1 month after stroke, using magnetic resonance imaging before and after intravenous gadolinium. We measured tissue enhancement for 30 minutes after intravenous gadolinium by two image analysis approaches (regions of interest and tissue segmentation). We compared the enhancement (leak) between lacunar and cortical patients, and associations with key variables, using general linear modeling. Results We recruited 51 lacunar and 46 cortical stroke patients. Signal enhancement after gadolinium was higher in lacunar than cortical stroke patients in white matter (p < 0.001) and cerebrospinal fluid (p < 0.003) by both analysis methods, independent of other variables. Signal enhancement after gadolinium was also associated with increasing age and enlarged perivascular spaces, but these did not explain the lacunar-cortical difference. Interpretation Patients with lacunar stroke have subtle, diffuse BBB dysfunction in white matter. Further studies are required to determine the relative contributions of BBB dysfunction and/or ischemia to the microvascular and brain abnormalities in lacunar stroke. Ann Neurol 2009;65:194,202 [source] Decreased lymphatic vessel counts in patients with systemic sclerosis: Association with fingertip ulcersARTHRITIS & RHEUMATISM, Issue 5 2010Alfiya Akhmetshina Objective Systemic sclerosis (SSc) is a connective tissue disease that is characterized by microvascular disease and tissue fibrosis. Progressive loss and irregular architecture of the small blood vessels are well characterized, but the potential involvement of the lymphatic vessel system has not been analyzed directly in SSc. This study was undertaken to assess whether the lymphatic vascular system is affected in SSc, and whether changes to the lymphatic vessels are associated with dystrophic changes and tissue damage in patients with SSc. Methods Lymphatic endothelial cells in skin biopsy samples from patients with SSc and age- and sex-matched healthy volunteers were identified by staining for podoplanin and prox-1, both of which are specifically expressed in lymphatic endothelial cells but not in blood vascular endothelial cells. CD31 was used as a pan,endothelial cell marker. Statistical analyses were performed using Kruskal-Wallis, Mann-Whitney U, and Spearman's rank correlation tests. Results The numbers of podoplanin- and prox-1,positive lymphatic vessels were significantly reduced in patients with SSc as compared with healthy individuals. The number of podoplanin-positive lymphatic precollector vessels was significantly lower in SSc patients with fingertip ulcers than in SSc patients without ulcers. Moreover, the number of lymphatic vessels correlated inversely with the number of fingertip ulcers at the time of biopsy and with the number of fingertip ulcers per year. The inverse correlation between lymphatic precollector vessel counts and fingertip ulcers remained significant after statistical adjustment for the blood vessel count, age, and modified Rodnan skin thickness score. Conclusion These results demonstrate a severe reduction in the number of lymphatic capillaries and lymphatic precollector vessels in patients with SSc. Patients with decreased lymphatic vessel counts may be at particularly high risk of developing fingertip ulcers. [source] Characteristics of patients with abnormal stress technetium Tc 99m sestamibi SPECT studies without significant coronary artery diameter stenosesCLINICAL CARDIOLOGY, Issue 11 2003Peter Ammann M.D. Abstract Background: Single-photon emission computed tomography (SPECT) sestamibi (MIBI) is an excellent tool for detection of coronary artery disease (CAD), preoperative risk assessment, and follow-up management after coronary revas-cularization. While the sensitivity of MIBI SPECT for detecting CAD has been reported to exceed 90%, the specificity ranges between 53,100%. Hypothesis: The study was undertaken to assess characteristics of patients with abnormal stress technetium Tc 99m sestamibi SPECT (MIBI) studies without significant coronary artery diameter stenoses (< 50%). Methods: Between January 1999 and November 2000, 270 consecutive patients were referred for coronary angiography due to reversible MIBI uptake defects during exercise. In 41 patients (15%; 39% women, mean age 59 ± 9 years), reversible MIBI uptake defects were assessed although coronary angiography showed no significant CAD. These patients were compared with age- and gender-matched patients with perfusion abnormalities (39% women, mean age 60 ± 9 years), due to significant CAD (coronary artery stenosis > 50%). Results: There were no significant differences between the two groups regarding body mass index, left bundle-branch block (LBBB), or method of stress test (dipyridamole in patients with LBBB or physical inactivity [n= 11] and exercise in all the others [n= 30]). Left ventricular hypertrophy (44 vs. 23%, p = 0.05) and left anterior fascicularblock (LAFB) (17 vs. 0%, p = 0.005) were more common in patients with perfusion abnormalities with no significant CAD, whereas ST-segment depression during exercise (17 vs. 37% p = 0.05) and angina during exercise (15 vs. 29%, p = 0.02) were significantly less common than in patients with abnormal MIBI perfusion studies and angiographically significant CAD. Sestamibi uptake defects during exercise were significantly smaller in patients without significant CAD than in matched controls with significant CAD (p < 0.0004). Conclusion: Of 270 consecutive patients, 41 (15%) referred to coronary angiography due to reversible MIBI uptake defects showed coronary artery stenoses <50%. Twenty-six (10%) of these presented angiographically normal coronary arteries. The significantly higher proportion of left ventricular hypertrophy and LAFB in patients with reversible MIBI uptake defects without significant CAD suggest microvascular disease, angiographically underestimated CAD, and conduction abnormalities as underlying mechanisms. [source] | ||||||||||