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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

11-Dehydro-TxB2 and 2,3-dinor-TxB2 are products of the two major pathways of thromboxane metabolism in man. In this study we compared urinary excretion of 2,3-dinor-TxB2 and 11-dehydro-TxB2 as indices of Tx biosynthesis in vivo. We performed three studies to assess i) the relative abundance of these two metabolites in the urine of healthy subjects, ii) their cellular origin under physiological conditions and iii) their relative formation during platelet activation. In healthy normal volunteers urinary 11-dehydro-TxB2 is more abundant than 2,3-dinor-TxB2 (792 +/- 119 pg/mg creatinine vs 106 +/- 21 pg/mg creatinine). Administration of a dose of aspirin selective for platelet cyclooxygenase (20 mg/day for 10 days) caused substantial and comparable suppression of both 11-dehydro-TxB2 (mean 82 +/- 4.9%) and 2,3-dinor-TxB2 (mean 79 +/- 6.9%). recovery of excretion of both metabolites after a nonselective aspirin regimen (325 mg BID for 3 days) corresponded to platelet life-span. Furthermore, excretion of both metabolites was increased in patients with severe atherosclerosis consistent with the known increase in platelet activation in this setting. Quantitative analysis of both urinary 11-dehydro-TxB2 and 2,3-dinor-TxB2 by GC-MS established that, in contrast to previous assumptions, 11-dehydro-TxB2 is the most abundant urinary metabolite of TxB2. The aspirin study demonstrates that platelets are the major source of both metabolites in urine, consistent with their increased excretion in severe atherosclerosis. Combined analysis of both metabolites will distinguish altered metabolism from increased biosynthesis of thromboxane A2.
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PMID:Paired analysis of urinary thromboxane B2 metabolites in humans. 368 81

The pathogenesis of atherosclerosis, a major cause of age-related mortality, remains poorly understood. Although platelets and their products, including thromboxane A2, may be of importance in this process, little is known about eicosenoid biosynthesis and platelet function with increasing age. In order to address the hypothesis that platelet activation increases with age, we measured various indices of platelet function in a group of apparently healthy individuals over the age of 50 years. The circulating platelet aggregate ratio, plasma beta-thromboglobulin and threshold aggregating concentration of arachidonic acid were similar to those in healthy subjects aged less than 40 years. Although the bleeding time (168 +/- 24 vs 300 +/- 24 seconds) was significantly (p less than 0.001) shorter in the older volunteers this may be unrelated to platelet function and merely reflect age related changes in skin and/or vascular function. To further assess platelet and vascular function in vivo, we measured excretion of the major thromboxane and prostacyclin metabolites in urine, 2,3-donor-thromboxane B2 (Tx-M) and 2,3-dinor-6-keto-PGF1 alpha (PGI-M). Both Tx-M (223 +/- 22 vs 152 +/- 19 pg/mg creatinine; p less than 0.005) and PGI-M (198 +/- 21 vs 121 +/- 13 pg/mg creatinine; p less than 0.005) excretion were significantly higher in the older volunteers. These subtle but significant changes in eicosenoid biosynthesis are consistent with the presence of platelet activation in vivo increasing with age in apparently healthy individuals.
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PMID:Eicosenoid biosynthesis and platelet function with advancing age. 375 55

Four patients are presented aged over 65 years in whom a state of cardiogenic shock was present due to myocardial infarction of the following localization: anterior in two and posterior in two. According to the parameters all patients satisfied the criteria of cardiogenic shock. Of the four patients three died. In all patients parameters of renal lesion were analyzed after establishment of diureses: sodium in urine, creatinine quotient in urine and plasma, osmolality of urine, osmolality quotient of urine and plasma, the renal failure index and the excretional fraction of filtered sodium. The parameters quoted were analyzed the day after diuresis was established. All parameters, apart from sodium in urine, indicated functional oliguria. In corroboration of this were the values of creatinine clearance which were determined the day after establishing diuresis, amounting in all patients to more than 20 ml/min./1.73 m2, i.e. ranging from 20.6 to 59.0 ml/min./1.73 m2. Of the cases which ended fatally all had fibroses and myocardial scars, apart from recent infarction of the myocardium, generalized atherosclerosis particularly of the coronary arteries, and in all patients hypertrophy of the left ventricle and dilatation of the whole heart. In one patient anaemic infarction of one kidney was found and in another acute tubular necrosis (with the renal failure index of 0.3 and the excretional fraction of filtered sodium of 0.2), while in third patient no renal changes were found.
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PMID:The characteristics of acute renal failure in cardiogenic shock in the elderly. 378 19

Forty male cynomolgus monkeys were fed a nutritionally complete diet containing butter and 0.5% cholesterol for 18 months to ensure development of atherosclerosis. Timefurone was administered daily at 10 mg/kg/day. Lipoprotein cholesterol parameters were measured every 4 weeks and clinical chemistries were done at approximately 8-week intervals. Low density lipoprotein cholesterol [LDL-C] was significantly reduced 24-45% at all time periods and total-C was lowered 17-23% at weeks 12, 16, and 24-40 in the timefurone group. Very low density lipoprotein cholesterol [VLDL-C] was increased 68-156% from weeks 40-78 and triglycerides [TG] were significantly elevated 52-220% on weeks 4-16, 24, 28, and 36-78 by timefurone. Timefurone caused small but significant changes in several clinical chemistry parameters including: creatinine, total bilirubin, albumin, glucose, serum glutamic-oxalacetic transaminase, and serum glutamic-pyruvic transaminase during the test. Significant reductions in arterial cholesterol were observed in thoracic aorta (-24%) and carotid arteries (-29%) in treated monkeys when compared to placebo. Arterial cholesterol in treated monkeys was positively correlated to LDL-C (R = 0.54, p less than or equal to 0.05). Timefurone, therefore, appears to have a significant beneficial effect against the development of atherosclerosis in cholesterol-fed male monkeys and possesses excellent potential for clinical experimentation.
Atherosclerosis 1985 Sep
PMID:Evaluation of timefurone, a new anti-atherosclerotic drug, for its effects on lipoprotein cholesterol in male cynomolgus monkeys fed an atherogenic diet for 18 months. 386 22

Atherosclerotic renal artery disease and the fibrous renal artery diseases are described with respect to their radiographic and clinical characteristics. In a retrospective review, serial renal arteriograms of 85 patients with atherosclerotic renal artery disease and 66 patients with the medial fibroplasia type of fibrous renal artery disease were analyzed to characterize their natural history. Atherosclerotic renovascular disease progressed in 37 patients (44%) with total arterial occlusion occurring in 14 patients (16%). Medial fibroplasia of the renal artery progressed in 22 patients (33%) with no patient progressing to complete occlusion. Reduction in kidney size and increase in serum creatinine were good clinical markers for progressive atherosclerotic renal artery disease, but failed to discriminate between progressive and nonprogressive medial fibroplasia. The adequacy of BP control did not correlate with progressive occlusive disease in patients with either renal artery atherosclerosis or medial fibroplasia. The clinical implications of these observations are discussed with a view toward renal revascularization or transluminal angioplasty for preservation of renal function.
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PMID:Natural history of atherosclerotic and fibrous renal artery disease: clinical implications. 388

Between 1970 and 1982, 50 patients (38 male and 12 female) underwent revascularization of 51 occluded renal arteries. Ages ranged from 8 to 71 years (mean 54.6 years). Occlusion was caused by atherosclerosis in 43 patients, fibromuscular dysplasia in three, chronic dissection in two, abdominal aortic coarctation in one, and neurofibromatosis in one. Contralateral renal artery occlusive disease occurred in 22 patients. Extrarenal atherosclerosis occurred in 44 patients. Mean preoperative serum creatinine level ranged from 0.5 to 8.4 mg/dl (mean 1.9 mg/dl). No patient required preoperative dialysis. Length of the involved kidney ranged from 8.4 to 14.5 cm (mean 11.5 cm). Indication for renal revascularization was hypertension in 49 patients and preservation of renal function in one. Renal artery bypass was performed in 36 patients, renal artery endarterectomy in six, transaortic endarterectomy in five, and reimplantation of the renal artery in three. Simultaneous revascularization of the contralateral renal artery was performed in 20 patients. There were three operative deaths. At hospital dismissal, hypertension had improved in 45 of 46 patients. Follow-up periods ranged from 4 months to 12 years (mean 50.2 months). Thirty-four patients remained normotensive, five still had less hypertension, and seven became worse. These data demonstrate that revascularization of an occluded renal artery can be effective in controlling hypertension and that this effect is durable in the majority of patients.
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PMID:The occluded renal artery: durability of revascularization. 396 46

The relation between chronic renal failure and the clinical and histological findings in normal-looking skin was studied in twenty-seven patients with minimum to marked rises of serum creatinine; eleven of these were on maintenance haemodialysis, and three were successful renal transplant recipients. Clinical findings, including pruritus and xerosis which affected 48% and 60%, respectively, of the patients overall, correlated strongly with severity of renal failure. Histological examination revealed endothelial cell activation and/or necrosis, basement membrane zone thickening, and reduplication of the basal lamina involving both venules and arterioles in all specimens. The microangiopathy was severe in 18 of 24 (75%) of the uraemic specimens, but severity correlated poorly with serum creatinine level, haemodialysis status, or known duration of renal failure, except that it was less severe in the first 2 years (p < 0.02). In contrast, the microangiopathy was very much less severe in the transplant recipients than in haemodialysed patients (p < 0.02) and, in the patient studied both before and after transplantation, changes regressed from severe to moderate within 2 months of transplantation. Other histological findings present in many specimens did not correlate with vessel changes. The findings establish the existence of a potentially reversible microangiopathy in normal-looking skin of patients with chronic renal failure. Further study is needed to determine if it reflects the same pathological process that underlies the development of accelerated atherosclerosis responsible for about half the deaths among patients on maintenance haemodialysis.
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PMID:Clinical and histological skin changes in chronic renal failure: evidence for a dialysis-resistant, transplant-responsive microangiopathy. 610 48

Prostacyclin is a potent vasodilator and platelet inhibitor produced by vascular endothelium. Endogenous production of prostacyclin under physiologic conditions is extremely low, far below the capacity of vascular tissue to generate this substance in response to stimulation in vitro. This may reflect a low frequency or intensity of stimulation of prostacyclin production. We postulated that if prostacyclin does act as an endogenous platelet-inhibitory agent, it should be produced in greater amounts in a clinical setting in which platelet-vascular interactions are likely to be increased. To test this hypothesis, we examined prostacyclin biosynthesis in patients with severe atherosclerosis and evidence of platelet activation in vivo. Excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha, a major urinary prostacyclin metabolite, was significantly higher in 9 patients with severe atherosclerosis and evidence of platelet activation (251 to 1859 pg per milligram of creatinine) than in 54 healthy volunteers (45 to 219 pg per milligram of creatinine; P less than 0.001). This difference represented an alteration in biosynthesis rather than in metabolism, since the fractional conversion of infused prostacyclin to the dinor metabolite was identical in both groups. Prostacyclin production may be low in healthy persons because there is almost no stimulus for its production but enhanced in patients with severe atherosclerosis as a consequence of platelet interactions with endothelium or other vascular insults. These observations are compatible with a role for prostacyclin as a local regulator of platelet-vascular interactions.
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PMID:Increased prostacyclin biosynthesis in patients with severe atherosclerosis and platelet activation. 623 83

Percutaneous transluminal angioplasty (PTA) was used to treat 109 patients with 141 renal artery stenoses, including 58 patients in whom medical management was unsuccessful. The initial success rate was 94%. Fifty-five patients had severe diffuse atherosclerosis and 40 had renal insufficiency. Thus far, 36 patients (50 stenoses) have undergone a total of 52 follow-up angiographic studies. Clinical data, including blood pressure response, were obtained in all cases. Only 7 of the 98 hypertensive patients failed to respond to PTA. Of the 11 patients treated primarily for renal insufficiency, 5 improved. Of the 29 hypertensive patients who also had elevated BUN and creatinine, renal function improved in 13. Altogether, 96 patients (88%) benefited from the procedure. Analysis of long-term results suggests that PTA should be the treatment of choice for fibromuscular dysplasia and short, segmental atherosclerotic lesions and could also prove helpful in improving renal insufficiency.
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PMID:Percutaneous transluminal angioplasty of the renal artery. Results and long-term follow-up. 623 77

From 1969 to 1979, 169 patients with two or more renal angiograms for renovascular disease (85 atherosclerotic, 75 fibrous, 9 atherosclerotic and fibrous) were reviewed in an attempt to characterize progression of disease and to determine clinical markers of progression. Progression of renal artery atherosclerosis was observed in 37 patients (44 per cent); progression to complete occlusion was observed in 14 patients (16 per cent). In the 66 patients with medial fibroplasia, progression was observed in 22 patients (33 per cent). Serial serum creatinine measurements in conjunction with measurements of kidney size may be used as markers of progressive atherosclerotic renovascular disease. These clinical markers did not represent progressive disease for individuals with medial fibroplasia.
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PMID:The natural history of atherosclerotic and fibrous renal artery disease. 646 47


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