A Rare Case of Intermittent Claudication Associated with Impaired Arterial Vasodilation.

Exercise-related intermittent claudication is marked by reduced blood flow to extremities caused by either stenosis or impaired vascular function. Although intermittent claudication is common in the elderly, it rarely occurs in the young and middle-aged individuals. Here, we report a case of exercise-related claudication in a 41-year-old woman, in the absence of overt vascular pathology. Using a series of imaging and functional tests, we established that her complaints were due to impaired arterial vasodilation, possibly due to a defect in nitrous oxide-mediated dilation. The symptoms were reversible upon administration of a calcium antagonist, showing reversibility of the vascular impairment. Identification of reversible vascular "stiffness" merits consideration in young and otherwise healthy subjects with claudication of unknown origin.

Early pregnancy circulatory adaptation and recurrent hypertensive disease: an explorative study.

INTRODUCTION: Hypertensive pregnancy disorders are assumed to be preceded by defective spiral artery remodeling. Whether this localized aberration at the implantation site affects the initial maternal systemic cardiovascular and renal adaptation to pregnancy is unclear. We explored in a high-risk population, whether the initial systemic maternal adaptation to pregnancy differs between women who do and do not develop a recurrent hypertensive disorder later on in pregnancy. METHODS: We enrolled 61 normotensive women with a previous hypertensive disorder of pregnancy and subdivided them into 2 subgroups, based on whether or not their next pregnancy remained uneventful (n = 33) or became complicated by a recurrent hypertensive disorder (n = 28). We measured before pregnancy and again at 18 ± 2 weeks of gestation cardiac output, blood pressure, plasma volume, creatinine clearance, and calculated total peripheral vascular resistance from cardiac output and blood pressure. RESULT: Both subgroups responded to pregnancy with an increase in cardiac output, plasma volume, heart rate, and creatinine clearance, and a decrease in blood pressure and total peripheral vascular resistance. Women who developed a recurrent hypertensive disorder differed from their counterparts with an uneventful next pregnancy by smaller pregnancy-induced increases in creatinine clearance (19% vs. 31%, P = .035) and cardiac output (10% vs. 20%, P = .035), respectively. CONCLUSION: The initial systemic cardiovascular and renal adaptations to pregnancy in women who develop a recurrent gestational hypertensive disorder differ from those in their counterparts with an uneventful next pregnancy by smaller rises in creatinine clearance and cardiac output.

OS105. Increased left ventricular mass index in normotensive formerly preeclamptic women is associated with the later development of chronic hypertension.

INTRODUCTION: A history of preeclampsia is associated with a 4-fold increased risk to develop chronic hypertension later in life. Interestingly, preeclampsia and chronic hypertension share the presence of increased left ventricular mass and increased left atrial diameter. Whether these increases are also present in the preclinical phase of chronic hypertension in women with a history of preeclampsia is still unknown. OBJECTIVES: To evaluate whether increased left ventricular mass index and/or left atrial widening in normotensive formerly preeclamptic women are associated with the development of chronic hypertension. METHODS: 324 Women with a history of preeclampsia, who were normotensive at the time of a diagnostic work-up 4 months postpartum, were included in this study. The tests employed included cardiac ultrasound and blood pressure measurements. Left ventricular mass was indexed (LVMi) for length in meters(2.7). To follow up on the health state, we send a health checklist to each screened former patient once every two years. The information of the diagnostic work-up and the one of the returned checklists were used for the statistical analysis by Uni- and Multivariate Cox regression analysis. RESULTS: Women who had developed chronic hypertension during a medium follow-up period of 6 years showed a significant Hazard Ratio (HR) of 1.11 (95% CI 1.03-1.18) for Left ventricular mass index, 1.13 (95% CI 1.06-1.20) for diastolic BP, 1.07 (95% CI 1.02-1.11) for systolic BP, 1.05 (95% CI 1.01-1.10) for Heart Rate and 0.215 (95% CI 0.055-0.848) for EA ratio. The multivariate top-down analysis showed a significant HR only for LVMi and diastolic BP, 1.08 (95% CI 1.00-1.18) and 1.10 (95% CI 1.02-1.19), respectively. CONCLUSION: Increased diastolic blood pressure and increased LVMi in normotensive formerly preeclamptic women are both associated with the development of chronic hypertension.

Estradiol inhibits mesangial cell-mediated oxidation of low-density lipoprotein.

It has been suggested that hyperlipidemia may contribute to the progression of renal disease via the deleterious effects of oxidized low-density lipoprotein (LDL) on the glomerular mesangium. Because estrogens possess potent antioxidant activity, we sought to determine whether sex hormones influence the oxidation of LDL by mesangial cells. Rat mesangial cells were incubated with LDL (200 micrograms/ml), and the extent of lipid oxidation was assessed by the generation of thiobarbituric acid reactive substances (TBARS), by increased electrophoretic mobility, and by enhanced uptake of mesangial cell-modified LDL by macrophages. A progressive rise in TBARS and an increase in electrophoretic mobility was observed on incubation of LDL with mesangial cells. Coincubation with estradiol (10 mumol/L) reduced TBARS generation by 46% at 36 hours (p < 0.01) and reversed the increase in relative electrophoretic mobility (1.25 +/- 0.07 vs 1.01 +/- 0.03, p < 0.05). LDL that had been oxidized by mesangial cells in the presence of estradiol (10 mumol/L) showed reduced uptake by macrophages when compared with LDL that had been oxidized by mesangial cells in the absence of estradiol (14 +/- 2 pmol/10(6) cells per hour vs 22 +/- 3 pmol/10(6) cells per hour, p < 0.05). In contrast, neither testosterone nor estrone had any effect on these parameters. We conclude that estradiol, by virtue of its antioxidant properties, inhibits mesangial cell-mediated oxidation of LDL and reduces the uptake of mesangial cell-modified LDL by macrophages.

Molecular characteristics of antibodies bearing an anti-DNA-associated idiotype.

Anti-double-stranded DNA antibodies are the hallmark of the disease systemic lupus erythematosus and are believed to contribute to pathogenesis. While a large number of anti-DNA antibodies from mice with lupus-like syndromes have been characterized and their variable region genes sequenced, few human anti-DNA antibodies have been reported. We describe here the variable region gene sequences of eight antibodies produced by Epstein-Barr virus (EBV)-transformed B cells that bear the 3I idiotype, an idiotype expressed on anti-DNA antibodies and present in high titer in patients with systemic lupus. The comparison of these antibodies to the light chains of 3I+ myeloma proteins and serum antibodies reveals that EBV transformation yields B cells producing antibodies representative of the expressed antibody repertoire. The analysis of nucleotide and amino acid sequences of these antibodies suggests the first complementarity determining region of the light chain may be important in DNA binding and that paradigms previously generated to account for DNA binding require modification. The understanding of the molecular genetics of the anti-DNA response requires a more complete description of the immunoglobulin germ line repertoire, but data reported here suggest that somatic diversification is a characteristic of the anti-DNA response.

Pathogenic anti-DNA antibodies in SLE: idiotypic families and genetic origins.

We have adopted an idiotypic approach to study the double stranded DNA (dsDNA) binding antibodies of systemic lupus erythematosus (SLE). Three anti-idiotypic reagents, 8.12, 3I, and F4, identify cross reactive idiotypes that are each expressed on anti-dsDNA antibodies in the sera of many patients with SLE. These idiotypic antibodies are implicated in the pathogenesis of SLE as they are present in immune complex deposits in the kidneys of patients with SLE glomerulonephritis. The autoantibody associated idiotypes are also expressed on antibodies that do not bind DNA. We are investigating the origin of the pathogenic anti-dsDNA antibodies of SLE by comparing the autoantibodies, the antibodies to foreign antigens, and the myeloma proteins that express each SLE associated idiotype. In conjunction with serological analysis of these idiotypic systems, molecular genetic studies indicate that both the 8.12 and the 3I autoantibody associated idiotypes may be germline encoded, while the F4 idiotype is generated by somatic mutation. The data further suggest that the antigenic specificity of the pathogenic anti-DNA antibodies of SLE is acquired through somatic mutation of germline immunoglobulin genes. By studying the regulation of genes capable of encoding pathogenic autoantibodies, in both SLE patients and non-autoimmune individuals, we may be able to elucidate the pathogenesis of autoimmune disease and begin to design more effective therapeutic interventions.