Altered relationship between body fat and plasma adiponectin in end-stage renal disease

Patients with end-stage renal disease (ESRD) show an inverse association between body mass index and risk of death from cardiovascular disease. Paradoxical epidemiology may suggest some beneficial effects of body fat in ESRD. Because an antiatherogenic adipocytokine adiponectin is increased in uremic plasma, we tested a hypothesis that, in ESRD, plasma adipocytokine profile may be less atherogenic or that the relationship between body fat and adipocytokines may be altered. The subjects were 103 patients with ESRD undergoing hemodialysis and 166 healthy subjects comparable in age and sex. We measured body fat mass by dual-energy x-ray absorptiometry and plasma levels of adiponectin and leptin by enzyme-linked immunosorbent assay. The ESRD group showed a significant increase in plasma adiponectin, leptin, and adiponectin/leptin ratio than the healthy subjects. Although sex and fat mass were significant factors correlating with plasma adiponectin level in the healthy group, none of these were significantly associated with plasma adiponectin in the patients with ESRD. In contrast, leptin showed significant relationships with sex and fat mass regardless of the presence of ESRD. Plasma adiponectin correlated negatively with plasma triglycerides and positively with high-density lipoprotein cholesterol in both healthy and ESRD groups, suggesting that uremic adiponectin retains its actions in favor of its antiatherogenicity. Thus, plasma adipocytokine profile was altered in ESRD, and the effects of body fat and sex on adiponectin were less significant in the patients with ESRD.     

Tissue plasminogen activator levels after single intracisternal injection in patients with subarachnoid hemorrhage

Tissue plasminogen activator (tPA) levels were investigated in the cisternal fluid of patients with subarachnoid hemorrhage treated with single intracisternal injection of recombinant tPA during radical surgery for ruptured aneurysms. Seven patients received different doses of tPA: two of 400 microg/ml, three of 500 microg/ml, one of 700 microg/ml, and one of 800 microg/ml in a total amount of 20 ml distilled water at pH 7. Cerebrospinal fluid samples were taken directly from the cisternal fluid at 15-minute incubation after injection, immediately after irrigation during surgery, and by lumbar tap 2 days after surgery. Cisternal tPA levels decreased to about 60% of the mean injected doses after 15-minute incubation. Simple linear regression analysis showed these tPA levels after incubation correlated with the initial doses. After copious irrigation with Ringer solution at pH 8, tPA levels decreased rapidly without correlation with the initial doses. After spinal drainage for 2 days, tPA levels further decreased by an order of 10(-4) to 10(-6) from the initial dose. These values were still greater than normal controls. The final values of tPA levels were not related to the initial dose. None of the patients suffered from systemic or wound complications. Cisternal tPA injection with increased doses and irrigation may be beneficial for the selective rapid removal of blood clots with controllable safety.     

The K469E polymorphism of the intercellular adhesion molecule-1 gene is associated with plasma fibrinogen level in type 2 diabetes

Intercellular adhesion molecule-1 (ICAM-1) is involved in inflammation and development of atherosclerotic change of vascular endothelium. The aim of the present study is to investigate whether K469E polymorphism of the ICAM-1 gene is associated with various clinical factors including plasma fibrinogen in patients with type 2 diabetes. ICAM-1 gene polymorphism was examined using polymerase chain reaction and restriction enzyme analysis in 360 type 2 diabetic patients. Plasma fibrinogen levels and other clinical variables were measured as well as circulating soluble ICAM-1 (sICAM-1) levels by enzyme-linked immunosorbent assay. The distribution of ICAM-1 genotypes, EE, EK, and KK, was not significantly different between type 2 diabetes and 152 healthy control subjects. Among 3 groups according to ICAM-1 genotypes in type 2 diabetes, no difference was found in adiposity, glycemic control, lipid profile, insulin sensitivity evaluated by homeostasis model assessment, or sICAM-1. Regarding fibrinogen, the patients with E allele showed significantly lower plasma fibrinogen levels in a dose-dependent manner (P = .033). Spearman rank correlation analyses revealed that ICAM-1 genotype showed significant correlation with plasma fibrinogen level (P < .001). In multiple regression analysis, ICAM-1 genotype was independent contribution factor of plasma fibrinogen level as well as high-density lipoprotein-cholesterol and urinary albumin excretion (R2 = 0.148, P < .001). In conclusion, K469E polymorphism of the ICAM-1 gene had impact on plasma fibrinogen level independently of other clinical factors in 360 type 2 diabetic patients, suggesting that fibrinogen is a candidate which links the ICAM-1 gene polymorphism to atherosclerosis.     

Regional arterial stiffness in patients with type 2 diabetes and chronic kidney disease

Increased arterial stiffness is an independent predictor of death from cardiovascular disease, and aortic stiffness is more predictive than stiffness of other arterial regions. Because little is known about the effect of chronic kidney disease (CKD) on regional arterial stiffness, pulse wave velocity (PWV) of four different arterial segments was measured in patients who had type 2 diabetes with and without various stages of CKD. A total of 434 patients had type 2 diabetes, and there were 192 healthy control subjects who were comparable in age and gender. GFR was estimated by the abbreviated Modification of Diet in Renal Disease equation. The patients with diabetes were classified into CKD stages by the definition of the Kidney Disease Outcomes Quality Initiative guidelines. PWV was measured in the heart-femoral, heart-carotid, heart-brachial, and femoral-ankle segments simultaneously using an automatic pulse wave analyzer. PWV of each arterial region was increased in patients who had diabetes without kidney damage and was increased further in a stepwise manner with the advanced stages of CKD. The increase in PWV was greater in the heart-femoral and heart-carotid regions than in the heart-brachial and femoral-ankle segments. However, after adjustment for age, BP, and other confounding factors using a multiple regression model, decreased GFR was independently associated with increased PWV of the heart-femoral region but not with PWV of other arterial segments. In type 2 diabetes, CKD was associated with increased stiffness of arteries, particularly of the aorta. The cross-sectional result may explain the increased risk for cardiovascular disease in CKD, although longitudinal studies are needed to confirm it.     

Regional arterial stiffness associated with ischemic heart disease in type 2 diabetes mellitus

Arterial stiffness is increased in type 2 diabetes mellitus, and diabetes preferentially affects arterial stiffness of the central (elastic, capacitive) over peripheral (muscular, conduit) arteries. We hypothesized that arterial stiffness of the central artery may be more closely associated with ischemic heart disease (IHD) than stiffness of peripheral arteries in type 2 diabetes mellitus. The subjects were 595 type 2 diabetes patients including 70 with IHD. Arterial stiffness was measured as pulse wave velocity (PWV) in the heart-carotid, heart-femoral, heart-brachial, and femoral-ankle regions. The PWV values of the four segments correlated with each other in patients without IHD. However, the correlations were less impressive in those with IHD, suggesting unequal stiffening of regional arteries in IHD. As compared with patients without IHD, the IHD group showed significantly higher PWV values of the four arterial segments, particularly of the heart-femoral region. The presence of IHD was significantly associated with higher heart-femoral PWV, and this association remained significant and independent of other factors in a multiple logistic regression analysis. Pulse pressure was more strongly correlated with PWV of the heart-femoral than other arterial regions. Thus, diabetic patients with IHD have increased stiffness of arteries, particularly of the aorta, supporting the concept that central arterial stiffness plays an important role in the development of IHD.     

Small dense low-density lipoprotein cholesterol concentration and carotid atherosclerosis

Low-density lipoprotein cholesterol (LDL-C) and the small dense LDL (SdLDL) phenotype are both predictors for ischemic heart disease. We examined whether cholesterol of SdLDL (SdLDL-C) is more closely associated with carotid artery intima-media thickness (CA-IMT), a surrogate measure of atherosclerosis, than LDL-C and other lipid parameters. The subjects were 326 consecutive participants including those with dyslipidemia, diabetes mellitus, hypertension, chronic kidney disease, and smokers. SdLDL-C was quantified by a newly developed precipitation method, and CA-IMT by high-resolution B-mode ultrasound. In univariate analysis, CA-IMT was most strongly correlated with SdLDL-C (Spearman's r=0.441, P<0.001), followed by apolipoprotein (apo) B, LDL-C, non-high-density lipoprotein cholesterol (Non-HDL-C), and plasma triglycerides (TG). HDL-C and apo A-I correlated inversely with CA-IMT. Non-lipid variables that were associated with CA-IMT were age, sex, presence of diabetes mellitus, presence of hypertension, estimate glomerular filtration rate (eGFR), and C-reactive protein (CRP). Even after adjustment for age, sex, diabetes mellitus, hypertension, smoking, eGFR and CRP, the positive association of CA-IMT with SdLDL-C remained significant, and again stronger than the associations with others lipid parameters. Further analyses revealed that the level of SdLDL-C was elevated in subgroups of the subjects including men, older subjects, smokers, those with higher CRP levels, those with diabetes mellitus, and hypertensive patients. These results indicate that SdLDL-C was the best marker of carotid atherosclerosis among the lipid parameters tested, and suggest that quantitative measurement of SdLDL-C gives useful information in the risk assessment for atherosclerotic disease.     

Thoracic meningocele in neurofibromatosis: CT and MR findings

A case of lateral intrathoracic meningocele incidentally found in association with neurofibromatosis Type 1 is presented. Magnetic resonance imaging proved most valuable in diagnosis.