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Association of umbilical placental vascular disease with fetal acute inflammatory cytokine responses.

OBJECTIVE: We examined the hypothesis that fetal proinflammatory cytokine release is a feature of placental vascular disease causing fetal compromise. We measured the concentrations of fetal proinflammatory cytokines interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and interleukin-8 (IL-8) in the presence of vascular disease in the umbilical placental villous circulation. Vascular disease was identified by high-resistance umbilical artery Doppler flow velocity waveform studies. METHODS: We measured levels of the inflammatory cytokines IL-6 and TNF-alpha and the chemokine IL-8 in fetal blood. Blood was collected from the umbilical vein at delivery, and serum was stored at -70C until assayed using chemiluminescent and enzyme-linked immunosorbent assay methods. We studied 36 normal pregnancies delivered by elective cesarean at term and 50 pregnancies with a high-resistance umbilical artery Doppler flow velocity waveform pattern indicative of fetal placental vascular disease delivered by elective cesarean because of potential fetal compromise. RESULTS: In the presence of umbilical placental vascular disease there were significantly higher levels of IL-6 (median 5.3 pg/mL, P <.05) and IL-8 (median 26.5 pg/mL, P <.01) compared with normal pregnancies (median value of IL-6 and IL-8 were below assay threshold). There was no difference for TNF-alpha, with the median results undetectable in both groups. CONCLUSION: We found higher concentrations of IL-6 and IL-8 in the fetal circulation in the presence of umbilical placental vascular disease.

Adult↗

New insights into elastin and vascular disease.

Elastin is synthesized and secreted by vascular smooth muscle cells and is the major extracellular matrix component deposited in the arterial wall. When last reviewed by this journal in 1994, the link between elastin and a rare occlusive vascular disease had just been established. Since that time, it has become increasingly clear that elastin is a critical autocrine factor that maintains vascular homeostasis through a combination of biomechanical support and biologic signaling. This review examines the complexity of elastin-smooth muscle cell interactions, and how new insights may impact understanding of the pathogenesis and treatment of vascular disease.

Animals↗

Effect of total leucocyte count on whole blood filterability in patients with peripheral vascular disease.

An abnormal filterability of whole blood through micropore membranes in vitro has been reported in peripheral vascular disease and has been thought to indicate abnormal red cell deformability. Blood from 68 patients with symptomatic peripheral vascular disease of varying severity and from 32 age-matched controls without a history of peripheral vascular disease was studied by the technique of whole blood filtration. In agreement with earlier findings, whole blood filterability was significantly reduced in patients with symptoms of vascular disease, but also their total leucocyte count was significantly higher than that of the controls. Variation in leucocyte count was found to affect significantly whole blood filterability, and the abnormal filterability in peripheral vascular disease could be entirely ascribed to this factor and not to an alteration in red cell deformability. The raised leucocyte count was not due to smoking but its cause could not be explained.

Aged↗

Extent and severity of atherosclerotic vascular disease in patients undergoing coronary angiography--the Kuwait Vascular Study.

Only a few angiographic studies have correlated the presence and severity of coronary artery disease with atherosclerosis in other arteries. The presence of disease in more than 1 area clearly has important implications on management. One hundred and seventy eight patients had angiographic evaluation of their peripheral arteries and abdominal aorta after routine diagnostic coronary angiography. The extent and severity of vascular disease was correlated with those of coronary artery disease. Of the 178 patients, 73.6% were men (mean age +/- sd was 52.93 +/- 10.12 years). Hypercholesterolemia (59%), systemic hypertension (56.7%) and diabetes mellitus (50.6%) were the major risk factors. Triple-vessel coronary artery disease was present in 48.9%, and 13.5% had normal coronaries. A new atherosclerotic vascular disease score, which reflects the presence and severity of atherosclerotic vascular disease elsewhere, was seen to correlate significantly with the extent of coronary artery disease. Of particular interest was the involvement of the first part of the vertebral artery in 41.6% of patients. The combined involvement of the abdominal aorta, renal artery, and iliac artery segments (together referred to as the lower body segment) was seen almost exclusively in those with 2- or 3-vessel coronary artery disease. Also there was a direct correlation between the extent of coronary artery disease and the score in the lower body segment as opposed to the upper body segment (subclavian, vertebral, and internal mammary arteries). The presence of atherosclerotic vascular disease correlated with the severity of coronary artery disease, particularly in respect to disease in the lower body segment. Thus early detection of such disease in the iliac or femoral arteries has a potential for early diagnosis of significant coronary artery disease.

Adult↗

Nitric oxide therapies in vascular diseases.

Endothelial dysfunction defined as the impaired ability of vascular endothelium to stimulate vasodilation plays a key role in the development of atherosclerosis and in various pathological conditions which predispose to atherosclerosis, such as hypercholesterolemia, hypertension, type 2 diabetes, hyperhomocyst (e) inemia and chronic renal failure. The major cause of the endothelial dysfunction is decreased bioavailability of nitric oxide (NO), a potent biological vasodilator produced in vascular endothelium from L-arginine by the endothelial NO synthase (eNOS). In vascular diseases, the bioavailability of NO can be impaired by various mechanisms, including decreased NO production by eNOS, and/or enhanced NO breakdown due to increased oxidative stress. The deactivation of eNOS is often associated with elevated plasma levels of its endogenous inhibitor, N(G) N(G)-dimethyl-L-arginine (ADMA). In hypercholesterolemia, a systemic deficit of NO may also increase the levels of low density lipoproteins (LDL) by modulating its synthesis and metabolism by the liver, as suggested by recent in vivo and in vitro studies using organic NO donors. Therapeutic strategies aiming to reduce the risk of vascular diseases by increasing bioavailability of NO continue to be developed. Cholesterol-lowering drugs, statins, have been shown to improve endothelial function in patients with hypercholesterolemia and atherosclerosis. Promising results were also obtained in some, but not all, vascular diseases after treatment with antioxidant vitamins (C and E) and after administration of eNOS substrate, L-arginine, or its cofactor, tetrahydrobiopterin (BH(4)). Novel strategies, which may produce beneficial changes in the vascular endothelium, include the use of natural extracts from plant foods rich in phytochemicals.

Animals↗

Antiphospholipid antibodies: a risk factor for occlusive ocular vascular disease in systemic lupus erythematosus and the 'primary' antiphospholipid syndrome.

Seven cases of occlusive ocular vascular disease affecting retinal and choroidal vessels were found among 84 consecutive patients with raised levels of anticardiolipin antibodies attending the lupus arthritis clinic at St Thomas's Hospital from 1985 to 1987. Six patients with systemic lupus erythematosus (SLE) and one with a 'primary antiphospholipid syndrome' had occlusive ocular vascular disease affecting a variety of vessels. This gives a prevalence of occlusive ocular vascular disease of 8% in this subgroup of patients, significantly higher than the 0.5-2.0% previously reported in patients with SLE. Four of these patients also suffered from cerebrovascular disease, supporting the previously documented association between occlusive ocular vascular disease and central nervous system disease in SLE. Additionally, other features of the antiphospholipid syndrome were frequently present. These findings suggest that patients with SLE and raised anticardiolipin antibodies have a higher risk of developing occlusive ocular vascular disease than has been previously reported.

Adult↗

Transcultural expression of subcortical vascular disease.

BACKGROUND: Many transcultural issues pertaining to subcortical vascular disease remain unanswered, and there is a relative paucity of research on stroke and dementia in non-Western societies. OBJECTIVE: To describe variations in the epidemiology of stroke and dementia, the recognition of dementia as an entity across cultures, the cultural specificity of screening tools and assessment instruments, and cultural influences on the management of stroke and dementia. RESULTS: Several studies have pointed out differences in the subtypes and outcomes from stroke across different world regions. Notably, non-Western populations may have a higher rate of hemorrhage, whilst in ischemic stroke subcortical vascular disease is predominant. A low prevalence of dementia has been demonstrated in many studies of non-Western populations. Factors proposed to account for this include protective family attitudes, a lower frequency of ApoE4 and the high mortality of non-Western dementia subjects, which may mask a high age-specific incidence rate. Other medical factors such as training, diagnostic skills, the availability of investigations and healthcare provision may also play a role, as would patient specific cultural attitudes towards ageing and mental health, together with differences in language, social customs and literacy. It has been suggested that there is a major difference between Western and Asian nations in the ratio of vascular dementia to Alzheimer disease. However, few epidemiological field studies have utilized neuroimaging and the reported rates for particular diagnoses should be interpreted cautiously. A recent population study in Japan, which utilized screening by neuropsychologists and CT scanning, showed that vascular dementia accounted for nearly half the cases of dementia. Subcortical vascular disease accounts for the majority of patients with vascular dementia (VaD). CONCLUSIONS: With the rapid demographic changes taking place in non-Western countries, non-communicable diseases such as dementia and stroke will increasingly come to dominate disease burden. More studies are required to prevent and treat these diseases.

Activities of Daily Living↗

Clinical features of MRI-defined subcortical vascular disease.

BACKGROUND AND PURPOSE: Vascular cognitive impairment and vascular dementia are now seen to extend much beyond the traditional multi-infarct dementia.A more homogeneous subtype is the subcortical ischemic vascular disease (SIVD). We applied magnetic resonance imaging (MRI) criteria based on research criteria for SIVD in a large cohort of patients with ischemic stroke. We compared clinical features of patients with SIVD and patients with other stroke type. SUBJECT AND METHODS: The study group comprised 337 of 486 consecutive patients aged 55 to 85 years who 3 months after ischemic stroke completed a comprehensive neuropsychological test battery and MRI, including structured medical, neurologic, and laboratory evaluations; clinical mental status examination; interview of a knowledgeable informant; detailed history of risk factors; and evaluation of stroke type, localization, and syndrome. RESULTS: Patients with SIVD (n = 86) more often had a history of progressive cognitive decline (22.8% vs. 6.9%, P = 0.0002), walking disorder before stroke (27.9% vs. 2.0%, P = 0.02), and urinary difficulties (12.8% vs. 5.6%, P = 0.028) in comparison with patients with other stroke type (n = 251). Of the study population, 107 (31.8%) had DSM-III dementia. The patients with SIVD more often had DSM-III dementia (40.7% vs. 28.7%, P = 0.04), had less severe stroke as measured by Scandinavian Stroke Scale (56.6 vs. 55.1, P = 0.03), were more dependent in activities of daily living (ADL) functions as measured by FAQ scale (8.9 vs. 5.4, P = 0.001), were more dependent in instrumental activities of daily living (IADL) functions as measured by the Lawton scale (5.5 vs. 6.3, P = 0.01), and were more depressed as measured by the Beck Depression Inventory (11.8 vs. 8.4, P = 0.0003) poststroke than the patients without SIVD. The main cognitive domain that differentiated the patients with SIVD from those without was executive dysfunction (51.2% vs. 38.7%, P = 0.04). According to multiple regression model, apractic-atactic gait disorder (odds ratio 2.82, 95% confidence interval 1.21-6.53), ADL functions (odds ratio 1.04, 95% confidence interval 1.01-1.08), and the Beck Depression Inventory (odds ratio 1.05, 95% confidence interval 1.02-1.09) related to SIVD. CONCLUSIONS: The most significant clinical features of MRI-defined SIVD were found to be apractic-atactic gait, impaired ADL functions, and depression.

Aged↗

Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease.

BACKGROUND: Hyperhomocysteinemia is a risk factor for vascular disease and potentially for dementia and depression. The most common cause of elevated homocysteine levels is deficiency of folate or vitamin B(12). However, patients with Parkinson disease (PD) may have elevated homocysteine levels resulting from methylation of levodopa and dopamine by catechol O-methyltransferase, an enzyme that uses S-adenosylmethionine as a methyl donor and yields S-adenosylhomocysteine. Since S-adenosylhomocysteine is rapidly converted to homocysteine, levodopa therapy may put patients at increased risk for vascular disease by raising homocysteine levels. OBJECTIVES: To determine whether elevations in plasma homocysteine levels caused by levodopa use are associated with increased prevalence of coronary artery disease (CAD), and to determine what role folate and vitamin B(12) have in levodopa-induced hyperhomocysteinemia. DESIGN/METHODS: Subjects included 235 patients with PD followed up in a movement disorders clinic. Of these, 201 had been treated with levodopa, and 34 had not. Blood samples were collected for the measurement of homocysteine, folate, cobalamin, and methylmalonic acid levels. A history of CAD (prior myocardial infarctions, coronary artery bypass grafting, or coronary angioplasty procedures) was prospectively elicited. We analyzed parametric data by means of 1-way analysis of variance or the t test, and categorical data by means of the Fisher exact test or chi(2) test. RESULTS: Mean +/- SD plasma homocysteine levels were significantly higher in patients treated with levodopa (16.1 +/- 6.2 micro mol/L), compared with levodopa-naïve patients (12.2 +/- 4.2 micro mol/L; P<.001). We found no difference in the plasma concentration of folate, cobalamin, or methylmalonic acid between the 2 groups. Patients whose homocysteine levels were in the higher quartile (>or=17.7 micro mol/L) had increased prevalence of CAD (relative risk, 1.75; 95% confidence interval, 1.08-2.70;P=.04). CONCLUSIONS: Levodopa therapy, rather than PD, is a cause of hyperhomocysteinemia in patients with PD. Deficiency of folate or vitamin B(12) levels does not explain the elevated homocysteine levels in these patients. To our knowledge, this is the first report that levodopa-related hyperhomocysteinemia is associated with increased risk for CAD. These findings have implications for the treatment of PD in patients at risk for vascular disease, and potentially for those at risk for dementia and depression.

Aged↗

Colorectal manifestations of collagen vascular disease.

BACKGROUND: The collagen vascular diseases are a collection of conditions, which are thought to be secondary to pathologic alterations in the immune system. Deposition of immune complexes in blood vessel walls resulting in either ischemia or thrombosis is the most widely accepted pathologic mechanism. The lack of familiarity with this subgroup of disease can lead to unnecessary surgical intervention. DATA SOURCES: A Medline search was performed of all the English-language literature. Further references were obtained through cross-referencing the bibliography cited in each work. CONCLUSION: Clinical manifestations are varied and complications include constipation, fecal incontinence, pseudoobstruction, perforation, hemorrhage, and mesenteric ischemia. Colorectal manifestations typically follow dermal presentations. Management should be conservative especially for pseudo-obstructions. Surgical intervention increases morbidity and should be chosen when absolutely necessary. Because of the high incidence of colorectal malignancies in patients with dermatomyositis, aggressive screening should be performed.

Connective Tissue Diseases↗

Management of collagen vascular diseases in childhood.

Collagen vascular diseases seen in children include systemic, discoid and neonatal lupus, dermatomyositis, scleroderma, juvenile rheumatoid arthritis, and, in rare cases, Sjogren's syndrome. Although these diseases are uncommon in children, when seen, they are associated with significant morbidity. This review describes the clinical features of each condition and provides an overview of treatment options now available. These include numerous systemic treatments which can be used as steroid-sparing agents.

Arthritis, Juvenile↗

[Better understanding of atheromatous ischemic renal vascular disease].

Atheromatous ischaemic renal vascular disease (AIRVD) comprises ischaemic renal disease, atheromatous disease of the large arteries and intra-renal atheromatosis. Cholesterol emboli and lesions of nephroangiosclerosis are often associated, affecting the two kidneys. It is an increasingly common cause of chronic renal failure in an aging population, affecting 12 to 14% of new patients requiring dialysis in the United States. Atheromatous stenoses are very progressive with a risk of renal atrophy; they are a marker of polyvascular disease, often detected during other angiographic investigation. Hypertension secondary to the stenosis, still incorrectly called renovascular hypertension, is, however rare, affecting less than 0.5% of hypertensives. For economic reasons, it is important to select patients who need complementary investigation. In view of the absence of specific signs of the pathology, the "presumptive" diagnosis is based on a range of clinical and biological results, especially in a high risk context. The method of investigation varies from team to team, depending on the availability of equipment, the experience of the operators and the patient himself. Duplex Doppler, spiral angioscan and magnetic resonance angiography are the most pertinent investigations for the management of AIRVD. When the diagnosis of renal artery stenosis has been made, the problem of revascularisation, the objective of which is to preserve or restore the functional nephronic mass, has to be treated to prevent progression to end stage renal failure. Although epidemiological and physiopathological evidence is in favour of revascularisation, only renal salvage procedures are imperative. Apart from these indications, the clinical benefits of revascularisation have not yet been demonstrated. In all cases, the control of associated risk factors is essential to maintain the success of revascularisation and slow down the progression of atheromatous disease.

Constriction, Pathologic↗

[Tubulointerstitial nephropathy secondary to collagen-vascular diseases].

Although collagen-vascular diseases mainly affect glomeruli and vessels, tubulointerstitial (TI) involvements as well, are frequently demonstrated histologically. In renal biopsy specimens from patients with lupus erythematosus, tubular atrophy, mononuclear (MN) cell infiltration into the interstitium and interstitial fibrosis are demonstrated in nearly 50% of cases. Immunoglobulins and complement components are sometimes deposited along tubular basement membrane, suggesting an immune-complex mediated mechanism. Infiltrating cells are mainly T cells, but the surface marker studies are not conclusive as to the subset of T cells responsible for the inflammation. As for Sjögren syndrome, TI changes and renal tubular acidosis are the prominent features of the disease. MN cell infiltration in the renal interstitium is also reported in patients with systemic vasculitis.

Collagen Diseases↗

Effect of dose of cyclosporine or FK506 and antithrombotic agents on cardiac allograft vascular disease in heterotopically transplanted hearts in rats.

BACKGROUND: We compared the severity of cardiac allograft vascular disease in rats treated with cyclosporine or FK506 and studied the effect of antithrombotic agents on cardiac allograft vascular disease. METHODS: One group each was treated with 2 and 5 mg/kg/day of cyclosporine. Two other groups were injected with heparin and dipyridamole, respectively, in addition to cyclosporine. Four other groups were similarly divided by dose of FK506 (0.1 or 0.25 mg/kg/day) and concomitant anticoagulant treatment. RESULTS: Grade of rejection and percentage stenosis of coronary arteries were lower in groups with high doses of immunosuppressive agents or with heparin. Major histocompatibility class II antigens were expressed by the endothelium of grafted hearts, and IgM and C3 were deposited in the intimal and medial layers in all groups except those administered the higher doses of immunosuppressive drugs. However, no remarkable differences in density of major histocompatibility class II antigens were found between groups demonstrating expression of these antigens. On the other hand, the intensity of IgM or C3 expression grew significantly as coronary stenosis increased in severity. CONCLUSIONS: A significant difference in severity of cardiac allograft vascular disease was not found between the groups treated with cyclosporine and FK506, and cardiac allograft vascular disease was almost entirely suppressed when doses of cyclosporine and FK506 sufficient to suppress graft rejection were administered. Our findings also showed that concomitant heparin administration reduced the extent of allograft rejection and the incidence of cardiac allograft vascular disease.

Animals↗

Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease.

BACKGROUND: Homocysteine is an independent risk factor for vascular disease and is associated with dementia in older people. Potential mechanisms include altered endothelial and hemostatic function. OBJECTIVE: We aimed to determine the effects of folic acid plus vitamin B-12, riboflavin, and vitamin B-6 on homocysteine and cognitive function. DESIGN: This was a factorial 2 x 2 x 2, randomized, placebo-controlled, double-blind study with 3 active treatments: folic acid (2.5 mg) plus vitamin B-12 (500 microg), vitamin B-6 (25 mg), and riboflavin (25 mg). We studied 185 patients aged >or=65 y with ischemic vascular disease. Outcome measures included plasma homocysteine, fibrinogen, and von Willebrand factor at 3 mo and cognitive change (determined with the use of the Letter Digit Coding Test and on the basis of the Telephone Interview of Cognitive Status) after 1 y. RESULTS: The mean (+/-SD) baseline plasma homocysteine concentration was 16.5 +/- 6.4 micromol/L. This value was 5.0 (95% CI: 3.8, 6.2) micromol/L lower in patients given folic acid plus vitamin B-12 than in patients not given folic acid plus vitamin B-12 but did not change significantly with vitamin B-6 or riboflavin treatment. Homocysteine lowering with folic acid plus vitamin B-12 had no significant effect, relative to the 2 other treatments, on fibrinogen, von Willebrand factor, or cognitive performance as measured by the Letter Digit Coding Test (mean change: -1; 95% CI: -2.3, 1.4) and the Telephone Interview of Cognitive Status (-0.7; 95% CI: -1.7, 0.4). CONCLUSION: Oral folic acid plus vitamin B-12 decreased homocysteine concentrations in elderly patients with vascular disease but was not associated with statistically significant beneficial effects on cognitive function over the short or medium term.

Aged↗

[Erythrocyte aggregation in vascular disease. Influence++ of hypertension].

In vascular diseases, when the vasomotor reserve is exhausted, microcirculation is strongly dependent on blood fluidity. For patients with vascular disorders, it was therefore decided to evaluate red blood cells (RBC) aggregation and disaggregation (SEFAM erythro-aggregometer) which are important factors determining blood viscosity in low flow areas. Our results show that, in essential hypertension (EH), RBC aggregation is significantly increased (+15%), and disaggregation is decreased (-20%). The highest frequency of troubles was found in EH. This observation led to exclusion of EH subjects in all the other studied pathological groups. When EH is excluded from a group of 70 patients with cerebrovascular disorders (CVD), we did not observe significant changes in RBC aggregation. However, in essential and post-thrombotic venous insufficiency there remains a significant increase in RBC aggregation (+10%) and a decrease in disaggregation (-13%). In diabetes, disaggregation is more disabled than for controls (-16%). In all these pathologies presence of EH magnifies the abnormalities, or makes them appear like in CVD. This study underlines the critical importance of taking the influence of hypertension into consideration when evaluating RBC aggregation in vascular pathology. The increase in RBC aggregability and in the shear resistance of the aggregates, when present in vascular pathology, is likely to add a burden to the circulatory system already hindered by a deficient vasomotor regulation system.

Adult↗

[Epidemiology of peripheral vascular disease in diabetics (author's transl)].

623 non-selected diabetic outpatients were screened by the Doppler-ultrasonic-method for peripheral vascular disease. Additional angiologic work up was performed to define the location of stenosis and obliteration. 15.9% of the diabetics were shown to have peripheral vascular disease and 57% of those denied claudication. 9% of the patients had signs of mediasclerosis. The predilection of peripheral vascular disease in diabetics for the arteries below the knee (peripheral type) was confirmed in our study. Patients with a pelvic or femoropopliteal type of peripheral vascular disease showed a high frequency of cardiovascular risk factors. An influence of the duration of diabetes on peripheral vascular disease was not evident. In contrast to this, a significant correlation (p less than 0.001) of the peripheral type of peripheral vascular disease-as well as of mediasclerosis--could be demonstrated with the diabetes of long duration. In patients with the peripheral type of peripheral vascular disease significantly more often higher blood sugar volues were found. Thus the quality of metabolic control seems to be of some importance for this form of diabetic macroangiopathy.

Adolescent↗

Usefulness of dipyridamole-thallium imaging in 257 patients with atherosclerotic vascular disease.

We evaluated the usefulness of dipyridamole-thallium imaging for the detection of ischaemic heart disease in 257 patients with atherosclerotic vascular disease (80 patients with arteriosclerosis obliterans, 81 patients with aneurysm of the abdominal aorta, 60 patients with aneurysm of the thoracic aorta and 36 patients with dissecting aortic aneurysm). Clinical evidence of ischaemic heart disease was found in 69 of 257 (27%) patients, including 32 patients with arteriosclerosis obliterans, 23 with aneurysm of the abdominal aorta, 9 with aneurysm of the thoracic aorta and 5 with dissecting aortic aneurysm. Dipyridamole-thallium imaging identified myocardial ischaemia in 49 of 69 (71%) patients with clinical evidence of ischaemic heart disease. Dipyridamole-thallium imaging showed positive results in 67 of 81 (83%) patients with aneurysm of the abdominal aorta. In patients with no clinical evidence of ischaemic heart disease, the results of dipyridamole-thallium imaging were positive in 39 of 188 (21%) patients. Dipyridamole-thallium imaging was positive in 90 of the 257 (35%) patients as a whole. When we combined the patients with positive dipyridamole-thallium imaging with those with negative dipyridamole-thallium imaging but who had clinical evidence of ischaemic heart disease, 42% of all patients had evidence of ischaemic heart disease. Our findings suggest that atherosclerotic vascular disease is strongly associated with ischaemic heart disease and that dipyridamole-thallium imaging is useful for the detection of ischaemic heart disease.

Aged↗