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A multicenter double blind controlled study of lipo-PGE1, PGE1 incorporated in lipid microspheres, in peripheral vascular disease secondary to connective tissue disorders.

Lipo-PGE1 is a drug preparation of PGE1 (prostaglandin E1) incorporated in lipid microspheres similar in properties to liposomes. A multicenter, placebo controlled, double blind test of lipo-PGE1 was carried out in patients with severe peripheral vascular disease secondary to diffuse connective tissue disorders. A total of 135 patients received a 90 min intravenous infusion of either 10 micrograms lipo-PGE1 or placebo every day for 4 weeks. A significant improvement was noted in the lipo-PGE1 group compared with the placebo group in the final overall improvement of peripheral vascular disease (p less than 0.001) and in the healing of ulcers (p less than 0.01), whereas, there was no difference in Raynaud's syndrome between the 2 groups. Side effects in the lipo-PGE1 group were few and were no different from controls. These results indicate that lipo-PGE1 at a low dose is beneficial in the treatment of peripheral vascular disease, and that lipid microspheres are useful as a drug delivery system for such purposes.

Adolescent↗

EDTA chelation therapy should be more commonly used in the treatment of vascular disease.

EDTA chelation therapy is safe, effective, and more economical than commonly used surgical treatments for vascular disease. This article includes evidence of effectiveness, mechanisms of action of EDTA, a discussion of studies that have been done regarding the therapy, and some brief case reports. The conclusion is that EDTA chelation therapy should be a therapeutic option for vascular disease, either by itself or in conjunction with standard protocols.

Chelation Therapy↗

The effect of pre-existing pulmonary vascular disease on the response to mechanical ventilation with PEEP following open-heart surgery.

The effects of mechanical ventilation with and without positive end-expiratory pressure (PEEP) on hemodynamic performance and blood-gas exchange were studied in ten patients following open-heart surgery. Ventilation at constant tidal volume (15 ml/kg body weight) with 10 cm H2O PEEP following aortic valve replacement (AVR) IN FIVE PATIENTs without pulmonary vascular disease was associated with the following significant changes: a rise in arterial Po2, a fall in the alveolar-arterial Po2 gradient when Fio2 = 1.0, decreases in calculated Qs/Qt and cardiac index. Using a similar pattern of ventilation following mitral valve replacement (MVR) in patients with elevated pulmonary vascular resistance, we found a significant decrease in cardiac index (but less than in the AVR group), a significant elevation of calculated physiologic deadspace (Vd/Vt) and no change in Qs/Qt. An hour after removal of PEEP, intravascular pressures, blood flow and blood-gas exchange values of all patients with AVR had returned to control levels; patients with MVR had persistently significantly low cardiac indices, while Vd/Vt returned to pre-PEEP values. These findings suggest that evaluation of responses to different ventilation patterns must take into account pre-existing V/Q abnormalities secondary to pulmonary vascular disease, particularly when these are secondary to chronic congestive heart failure. Following AVR, Qs/Qt changed in the same direction as cardiac index (CI) irrespective of ventilatory pattern: CI decreased and rose as CI increased. The authors conclude that with increasing severity of pulmonary vascular disease, changes in airway pressure will have an unpredictable effect on cardiac index unless the level of myocardial competence is taken into account. In the presence of ventricular failure, changes in pleural (and therefore transmural) pressures will be minimal compared with the high filling pressures and exert no influence on stroke volume. Although pulmonary venous hypertension was more pronounded in the MVR than in the AVR group, there was no significant difference between the postoperative values for Qs/Qt (Fio2 = 1.0), a condition probably fostered by marked differences in pre-existing V/Q.

Aged↗

Medical treatment of peripheral vascular disease: good or bad?

The majority of patients with intermittent claudication are treated conservatively; smoking must be stopped and exercise therapy commenced. There are various classes of drugs that are widely prescribed for the treatment of peripheral vascular disease. In this editorial the medical treatment of peripheral vascular disease is claimed to achieve at least one of three goals: (1) improvement of the functional capability; (2) inhibition of the progression of the atherosclerotic and anatomical lesions; (3) reduction of the cardiac and cerebrovascular morbidity and mortality. Guidelines are given for well controlled trials for newly developed drugs for the treatment of peripheral vascular disease in the future.

Arterial Occlusive Diseases↗

Soluble P-selectin in hyperlipidaemia with and without symptomatic vascular disease: relationship with von Willebrand factor.

Soluble P-selectin (CD62P) may arise from platelets, the endothelium, or both, and raised levels are found in those with thrombotic disease and atherosclerosis. To determine whether these increased levels in atherosclerosis are related to hypercholesterolaemia, blood samples were obtained from 86 patients (43 with symptomatic vascular disease) attending a hypercholesterolaemia clinic, and 86 age- and sex-matched controls. Parallel measurement of endothelial cell product von Willebrand factor helped define the origin of sP-selectin. Using ELISAs, soluble P-selectin was higher (median 290 ng/ml, range 80-735, P < 0.05) in patients with vascular disease than in both patients with uncomplicated hypercholesterolaemia (median 210 ng/ml, range 55-550), and controls (median 190 ng/ml, range 48-500). Von Willebrand factor was raised in both patients with uncomplicated hypercholesterolaemia (115 +/- 26 IU/dl, P < 0.05) and patients with hypercholesterolaemia and vascular disease (129 +/- 32 IU/dl, P < 0.02) compared with controls (102 +/- 30 IU/dl). Levels of soluble P-selectin did not correlate with von Willebrand factor, total low-density-lipoprotein (LDL) or high-density-lipoprotein (HDL) cholesterol or triglycerides levels, blood pressure or smoking, but von Willebrand factor correlated with LDL cholesterol (r = 0.42, P < 0.05). We conclude that plasma lipoproteins are not a major influence on levels of soluble P-selectin.

Adult↗

Oral hydralazine in patients with pulmonary vascular disease secondary to congenital heart disease.

Two patients with pulmonary vascular obstructive disease secondary to congenital heart disease were evaluated hemodynamically before and during oral hydralazine therapy. Both patients were assessed postoperatively and had no significant residual shunts. Pulmonary vascular resistance failed to decrease, and an increase in pulmonary arterial pressure occurred because of increased cardiac output secondary to systemic arteriolar dilatation. These responses were sufficiently consistent to warrant a warning against the use of oral hydralazine except under controlled conditions in patients with secondary pulmonary vascular obstructive disease.

Administration, Oral↗

Nutritional aspects and possible pathological mechanisms of hyperhomocysteinaemia: an independent risk factor for vascular disease.

Numerous case-control and prospective studies have identified elevated plasma homocysteine as a strong independent risk factor for cerebovascular, cardiovascular and peripheral vascular disease. Homocysteine is formed as a result of the breakdown of the dietary amino acid methionine. Once formed, homocysteine is either remethylated to methionine, or undergoes a trans-sulfuration reaction to form cysteine. The re-methylation of homocysteine to methionine is dependent on three B-vitamins, i.e. riboflavin, vitamin B12 and folate. The second pathway of homocysteine metabolism is the trans-sulfuration pathway which requires both vitamin B6 and riboflavin for its activity. Thus, up to four B-vitamins are required for intracellular homocysteine metabolism. Many studies have noted strong inverse relationships between homocysteine levels and the status of both vitamin B12 and folate. However, the relationship between vitamin B6 status and homocysteine is still uncertain. Similarly, numerous intervention studies have demonstrated effective lowering of homocysteine levels as a result of folate and vitamin B12 supplementation, while the homocysteine-lowering ability of vitamin B6 is unclear. Even though riboflavin plays a crucial role in both the trans-sulfuration and remethylation pathways of homocysteine metabolism, the relationship between riboflavin status and homocysteine levels has not been investigated. The exact mechanism that explains the vascular toxicity of elevated homocysteine levels is unknown at present, studies indicate that it is both atherogenic and thrombogenic. To date, no randomized clinical trial has demonstrated that lowering of homocysteine levels is beneficial in terms of reducing the prevalence of vascular disease. It is probable, however, that optimal B-vitamin status is important in the prevention of vascular disease.

Arteriosclerosis↗

The Bard Rotary Atherectomy System (BRAS): initial experience in patients with peripheral vascular disease.

Sixteen patients with a mean age of 65.4 +/- 9.8 years and suffering from peripheral vascular disease underwent peripheral atherectomy using a new mechanical device--the BARD Rotary Atherectomy System (BRAS). The BRAS is an "over the wire" system that consists of a spiral guidewire and a handheld motor drive unit, which rotates at 1,500 rpm. Prior to the procedure angiography demonstrated the presence of 18 obstructions (1 tibial, 2 popliteal, 15 superficial femoral arteries) with a mean stenosis of 95.7 +/- 8%. Successful atherectomy was achieved in 16 of 18 lesions and resulted in an 89% immediate success rate and a significant (P less than 0.01) reduction of stenosis to 37.8 +/- 12.5%. There were no significant complications. The excised and removed material embedded over the spiral guidewire demonstrated the presence of fibrotic tissue, fatty lesions, and calcium deposits. Medial or adventitial layers were not present in the removed atherosclerotic material. Mean ABI was significantly (P less than 0.01) increased from 0.38 +/- 0.17 to 0.55 +/- 0.21 following atherectomy. Angiographic follow-up obtained in ten patients 8.8 +/- 5.2 months following the procedure demonstrated restenosis in six of those ten patients. The ABI at this time remained unchanged. These results demonstrated that the new BRAS mechanical atherectomy system is feasible and safe for recanalization of severely stenosed arteries in patients with peripheral vascular disease.

Aged↗

Low serum folate but normal homocysteine levels in patients with atherosclerotic vascular disease and matched healthy controls.

Mild hyperhomocysteinemia has been considered a cardiovascular risk factor. However, recent prospective studies have not demonstrated that hyperhomocysteinemia or the underlying genetic defect on methylentetrahydrofolate reductase is associated with a higher risk of coronary or peripheral artery disease. We compared serum homocysteine, folate, and vitamin B(12) levels of patients with coronary and peripheral vascular disease with those of age- and sex-matched healthy individuals. Subjects taking multivitamins, with diabetes mellitus, or serum creatinine levels over 1.5 mg/dL were excluded from the study. Homocysteine was measured by fluorimetric high-performance liquid chromatography. Serum folate and vitamin B(12) levels were measured by an ion-capture method. We studied 32 patients with peripheral vascular disease (10 female), aged 69.6 +/- 11 y, 24 age- and sex-matched control subjects, 52 patients with coronary artery disease (7 female), aged 59.5 +/- 10.4 y, and 42 age- and sex-matched control subjects. Serum homocysteine levels were 11.7 +/- 7.4 and 9.3 +/- 4.5 micromol/L in vascular patients and in the control counterparts, respectively (not significant). The levels for coronary patients and the control counterparts were 9.0 +/- 3.9 and 8.6 +/- 3.6 micromol/L, respectively (not significant). Folate levels were 4.48 +/- 2.42 and 7.14 +/- 4.04 ng/mL in vascular patients and control subjects, respectively (P < 0.02); the levels in coronary patients and control counterparts were 5.15 +/- 1.9 and 6.59 +/- 2.49 ng/mL, respectively (P < 0.01). No differences in vitamin B(12) or tocopherol levels were observed between patients and control subjects. There were no differences in homocysteine levels, but lower serum folate levels were observed when comparing patients with atherosclerotic vascular disease and healthy control subjects.

Aged↗

Daily modifications of plasma fibrinogen platelets aggregation, Howell's time, PTT, TT, and antithrombin II in normal subjects and in patients with vascular disease.

The possibility of occurrence of daily variations in blood fibrinogen levels, platelets aggregation. Howell's time values and values for PTT, TT and antithrombin III was explored in 10 healthy subjects and in 10 patients with vascular disease. In normal subjects blood fibrinogen, platelets aggregation in ADP, PTT, Howell's time and TT values showed statistically significant daily variations, while the AT III values showed no significant variations over the 24-h cycle. In patients with vascular disease, on the other hand, the daily variations of the fibrinogen blood levels, of the maximum amplitude of platelets aggregation and of the Howell's values were not detected. In fact, the first two parameters remained consistently high and the third parameter remained consistently low throughout the 24-h cycle. In contrast, the PTT as well as the TT values in these patients showed statistically significant daily variations but with time patterns different than those found in normal subjects. Also, unlike to what obtained in healthy subjects, the AT III values in patients with vascular disease showed highly significant variations over the period of 24-h.

Antithrombin III↗

Cryopreserved aortic homograft replacement in 3 patients with noninfectious inflammatory vascular disease.

OBJECTIVE: Although mechanical prosthetic heart valves are most commonly used for aortic valve replacement in patients with aortic regurgitation due to noninfectious inflammatory vascular disease, postoperative perivalvular leakage and/or detachment of the prosthetic valve occurs due to the fragility of the aortic annulus. Aortic root replacement with cryopreserved homografts is reported to be useful in such patients. METHODS: Three patients having aortic regurgitation associated with severe long standing noninfectious inflammatory vascular disease-2 patients with Takayasu's arteritis and 1 patient with Behçet disease--had the aortic root replacement by a cryopreserved aortic homograft valve and conduit. RESULTS: All surgery was successful and the postoperative course uneventful. Echocardiography showed neither aortic regurgitation nor graft detachment at 6-39 months after operation. CONCLUSIONS: Homograft valve and conduit replacement is appropriate in patients with aortic regurgitation associated with noninfectious inflammatory vascular disease, with mid-term results favorable.

Adult↗

Common femoral artery volume flow in peripheral vascular disease.

Common femoral artery volume flow was measured at rest and during postocclusive reactive hyperaemia in 80 normal subjects and 67 patients with radiological evidence of occlusive peripheral vascular disease. At rest, means(s.d.) common femoral artery volume flow in normal subjects (344(135) ml/min) and all patients with peripheral vascular disease (401(168) ml/min) was not significantly different. During postocclusive reactive hyperaemia, mean(s.d.) peak flow was significantly higher in normal subjects (1951(438) ml/min) than in patients with peripheral vascular disease (996(457) ml/min) (P less than 0.01). Common femoral artery volume flow in patients with critical ischaemia and intermittent claudication did not differ at rest but mean(s.d.) peak flow in patients with critical ischaemia (697(276) ml/min) was significantly lower than in claudicants (1131(447) ml/min) (P less than 0.01). Mean(s.d.) resting common femoral artery volume flow in limbs with femoropopliteal disease (457(185) ml/min) was significantly greater than that in limbs with occlusion of the aortoiliac segment (308(130) ml/min) (P less than 0.01). However, this difference did not persist during postocclusive reactive hyperaemia. A hyperaemic index, calculated from the hyperaemic responses to below knee and whole limb ischaemia, was used to quantify segmental perfusion during postocclusive reactive hyperaemia. The mean(s.d.) value in normal subjects, 46(9) per cent, and in those with aortoiliac disease, 52(12) per cent, indicated approximately equal perfusion of the above and below knee limb segments. In those with femoropopliteal disease the mean(s.d.) hyperaemic index was 17(13) per cent, revealing relative hypoperfusion of the below knee segment.

Adult↗

EDTA chelation therapy in the treatment of vascular disease.

Ethylenediamine tetraacetic acid (EDTA) chelation therapy has been used for decades for the treatment of vascular disease, alone or in combination with other treatments. This article includes a historic review of the research literature, current evidence of effectiveness, potential mechanisms of action of EDTA, and some brief case reports. The authors conclude that EDTA chelation therapy is a valuable therapeutic option for vascular disease, either alone or in conjunction with standard treatment protocols.

Chelating Agents↗

Vasodilator drugs in peripheral vascular disease.

The use of vasodilator drugs in peripheral vascular disease is reviewed. Discussed are actions and efficacy of direct-acting drugs such as isoxsuprine, papaverinek niacin and cyclandelate; the beta-receptor stimulating drug, nylidrin; and drugs which affect the sympathetic nervous system, such as tolazoline, reserpine, guanethidine, methyldopa, ergot alkaloids and alcohol. Both animal and clinical studies reveal little evidence of the effectiveness of vasodilator drugs in the treatment of obstructive arterial disease. In some patients with vasospastic diseases, vasodilators which act upon the sympathetic nervous system (reserpine and guanethidine) may have an ameliorating effect by increasing cutaneous capillary blood flow.

Arterial Occlusive Diseases↗

Is the perceived association between Chlamydia pneumoniae and vascular diseases biased by methodology?

Inter- and intralaboratory inconsistencies in detection rates of Chlamydia pneumoniae in vascular specimens have been demonstrated. In this study, 66 vascular tissue specimens from 66 patients with vascular disease were tested by three PCR assays: a 16S PCR-based reverse line blot (RLB) assay, a single-step PCR, and a nested PCR. Also, we explored the impacts of different DNA polymerase enzymes on the results based on gel electrophoresis and hybridization. The PCR results by gel electrophoresis in the single-step PCR depended on which DNA polymerase was used. All samples were negative with AmpliTaq Gold DNA polymerase, and 54.5% (36 of 66) were positive with the conventional Taq DNA polymerase. All samples were negative after hybridization with a C. pneumoniae-specific probe. In the nested PCR, all specimens were negative by gel electrophoresis and after hybridization. The RLB assay failed to detect C. pneumoniae in any specimen; however, 20 specimens were Chlamydia sp. positive. The sequence analysis of six of these samples demonstrated Chlamydia-like organisms. RLB detected Chlamydia sp. DNA in water and in the elution buffer after passage of the Qiagen columns (11 of 40). This study identified factors that may influence the detection of C. pneumoniae DNA in vascular tissues and consequently bias the perception of a link between C. pneumoniae and vascular diseases. The following are strongly recommended: to use DNA polymerases that have to be activated, to decontaminate with dUTP-uracil-DNA glycosylase, to hybridize with specific probes, to include sufficient controls, and to use molecular grade water.

Base Sequence↗

Is type 2 diabetes mellitus a vascular disease (atheroscleropathy) with hyperglycemia a late manifestation? The role of NOS, NO, and redox stress.

BACKGROUND: Cardiovascular disease accounts for at least 85 percent of deaths for those patients with type 2 diabetes mellitus (T2DM). Additionally, 75 percent of these deaths are due to ischemic heart disease. HYPOTHESIS: Is type 2 diabetes mellitus a vascular disease (atheroscleropathy) with hyperglycemia a late manifestation? The role of NOS, NO, and redox stress. TESTING OF THE HYPOTHESIS: The vulnerable three arms of the eNOS reaction responsible for the generation of eNO is discussed in relation to the hypothesis: (1) The L-arginine substrate. (2) The eNOS enzyme. (3) The BH4 cofactor. IMPLICATIONS OF THE HYPOTHESIS: If we view T2DM as a vascular disease initially with a later manifestation of hyperglycemia, we may be able to better understand and modify the multiple toxicities associated with insulin resistance, metabolic syndrome, prediabetes, overt T2DM, and accelerated atherosclerosis (atheroscleropathy). The importance of endothelial nitric oxide synthase, endothelial nitric oxide, tetrahydrobiopterin (BH4), L-arginine, and redox stress are discussed in relation to endothelial cell dysfunction and the development and progression of atheroscleropathy and T2DM. In addition to the standard therapies to restore endothelial cell dysfunction and stabilization of vulnerable atherosclerotic plaques, this article will discuss the importance of folic acid (5MTHF) supplementation in this complex devastating disease process. Atheroscleropathy and hyperglycemia could be early and late manifestations, respectively, in the natural progressive history of T2DM.

Journal Article↗

[The significance of inflammatory vascular diseases].

Out of the from angiological points of view most important inflammatory vascular diseases (obliterating endangiitis, giant cell arteriitis, Takayasu's disease) epidemiological data are compiled. Remarkable is the increasing part of female patients in endangiitis. Furthermore it is referred to the particular functional situation in these vascular diseases, which results from the localisation of a peripheral occlusion, insufficient formation of collaterals or disturbed rheology.

Aortic Arch Syndromes↗