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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the past 20 years treatment appears to have had a major impact on all forms of cerebral vascular disease. Morbidity and mortality from strokes have declined nearly 50% in developed countries. Modern imaging techniques, methodology, and biostatistics have identified risk factors and refined clinical trials such that we question all previous studies of stroke management. Control of moderate and severe hypertension has significantly lowered stroke rates. In borderline and mild hypertension the decision to treat is influenced by other stroke risk factors including diabetes mellitus, cigarette smoking, ischaemic heart disease, plasma lipid levels, gout, haematocrit, and body weight. Current data indicate that anticoagulants are of no value, or hazardous, in atherothrombotic strokes; of unknown value in transient ischaemic attacks; of dubious value in evolving strokes; and beneficial in cardiac embolism. The cardiac causes, including mural thrombus, unstable arrhythmias, and mitral valve prolapse should be actively sought. Aspirin, as the prototype anti-platelet agent, holds promise in transient ischemic attacks and minor strokes at both small and moderate dosages. Ticlopine is now being critically evaluated in America. Use of cerebral vasodilators should be abandoned. Enthusiasm in the use of streptokinase and urokinase has been dampened by the conversion of ischemic infarcts into haemorrhagic infarcts. In subarachnoid haemorrhage epsilon-aminocaprioc acid is useful although hazardous, in preventing rebleeding. Certain calcium ion channel blockers are promising in the reduction of vasopasm. Since the November 1985 article in the new England Journal of Medicine on the failure of external-to-internal carotid arterial bypass to reduce the risk of ischemic stroke, the swing is back to conservative management.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Advances in the medical management of cerebral vascular disease. 331 47

Patients with diabetes are predisposed to microvascular disease. In the retina and brain, this is characterized by neovascularization and new capillary formation. Because of the potential importance of plasmin generation in these processes, we evaluated the effect of elevated glucose concentrations on expression of plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and urokinase (uPA) in cultured bovine brain endothelial cells (BBEC) versus cultured bovine aortic endothelial cells (BAEC). We observed that BBEC PAI-1 mRNA levels were decreased fivefold in cells cultured in media containing 20 mM glucose compared with BBEC cultured in media with 5.5 mM glucose, whereas expression of PAI-1 mRNA in BAEC, bovine mesenteric endothelial cells, and human umbilical vein endothelial cells was not modulated under these conditions. Expression of PAI-1 protein was also inhibited by growth of BBEC in elevated glucose, but the effect was less marked than at the mRNA level. Elevated glucose did not decrease expression of PAI-1 protein by BAEC. Withdrawal of acidic fibroblast growth factor enhanced expression of PAI-1 mRNA and protein in BBEC. Expression of tPA mRNA was not affected by the glucose concentration of the medium, and uPA mRNA was not detected in our BBEC cultures. A decrease in the local tissue activity of PAI-1 by elevated glucose concentrations, with no effect on tPA or uPA expression, would lead to an increase in the plasmin activity and thereby predispose neural tissues, such as the cerebrum and retina, of diabetic patients to neovascularization.
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PMID:Plasminogen activator inhibitor-1 expression by brain microvessel endothelial cells is inhibited by elevated glucose. 751 64

The purpose of this prospective study was to determine the value of intraoperative intra-arterial fibrinolytic therapy (IIFT) in patients with acute arterial ischemia as an adjunct to mechanical thromboembolectomy. Sixty-six femoropopliteal or distal acute arterial occlusions were assessed by means of arteriography and Doppler imaging pre- and postoperatively. Two groups of patients were compared: one (n = 35) in which mechanical thromboembolectomy was applied as the single technique and another (n = 31) in which 250,000 IU of urokinase diluted in 250 ml of normal saline solution was instilled at the end of mechanical thromboembolectomy over a 30-minute period with the arterial inflow occluded. Candidates for IIFT were selected according to a nonrandomized method. Intraoperative arteriography showed residual thrombus in 20 (30.3%) patients and unsuspected arterial lesions in 23 (34.8%). Thrombosis recurrence was associated with residual thrombus (p < 0.001) and amputation (p < 0.001). The ankle/brachial index increased significantly (p < 0.05) in the patients who received IIFT (0.88 +/- 0.03) in comparison with those who underwent mechanical thromboembolectomy (0.75 +/- 0.05). Although the percentages of distal revascularization and amputation did not differ significantly between the two groups, quantitatively the results were better in the IIFT group (80.65% success and 9.68% failure) compared to the mechanical thromboembolectomy group (60% success and 22.86% failure). There was no bleeding due to IIFT. Significant variables in our study were diabetes (p < 0.05), the time period of 12 to 24 hours before the surgery (p < 0.05), and the severity of the ischemia in association with rest pain (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraoperative fibrinolytic therapy for salvage of limbs with acute arterial ischemia: an adjunct to thromboembolectomy. 778 4

Urokinase (u-PA) dissolves and removes fibrin deposits in the renal secretory pathways in various renal diseases. During pregnancy nephropathy creates a problem in preeclampsia and diabetes, but the underlying mechanism of glomerular damage is different. Preeclamptic nephropathy is characterized as 'glomerular endotheliosis' with hypertrophy of the intracapillary cells, and diabetic nephropathy as 'glomerulosclerosis' with hyaline deposits. The role of fibrin deposition for the etiology of renal damage in preeclampsia is controversial. Changes of the urinary secretion of u-PA may reflect the type of glomerular damage. Our hypotheses were that renal insufficiency is associated with a low u-PA activity in both conditions, and that severe disease is parallel to declining concentrations of u-PA. We compared the glomerular filtration rate, S-Creatinine and S-Urate with urinary u-PA excretion in 24 hypertensive and 20 diabetic pregnant women. In diabetic patients, a low u-PA concentrations was associated with an impaired renal function. In hypertensive pregnancy, the u-PA excretion did not reflect the severity of the hypertensive disease or renal function. No association was found between u-PA excretion and renal function post partum in any group. We conclude that renal urokinase activity plays a role for renal function in diabetic but not in hypertensive pregnancy.
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PMID:Renal function and urinary urokinase in hypertensive and diabetic pregnancies. 782 57

To elucidate a role of tPA, uPA and PAI-1 for the development of diabetic glomerulosclerosis, the effect of high glucose concentration on the production of both basal and thrombin-mediated tPA, uPA and PAI-1 antigens from human mesangial cells was investigated. The culture of mesangial cells in the presence of high glucose (33 mM) for 11 days resulted in an increase in the synthesis of tPA and uPA when compared with that in normal glucose concentration (5 mM). In contrast, the cells grown in high glucose produced less PAI-1 than those in normal glucose. Thrombin stimulated dose-dependently the production of tPA, uPA and PAI-1 from the cells grown in either 5 or 33 mM glucose. However, the magnitude of the increase in tPA, uPA and PAI-1 from the cells grown in high glucose was less than that in normal glucose. These results suggest that the plasmin activity in mesangial cells may increase under a high glucose condition, leading to increased proteolysis of mesangial matrix. In addition, either fibrinolysis or proteolysis mediated by thrombin may be altered by high glucose concentration. Therefore, it is postulated that the turnover of mesangial matrix may be increased in diabetic nephropathy.
Diabetes Res Clin Pract 1994 May
PMID:A high concentration of glucose alters the production of tPA, uPA and PAI-1 antigens from human mesangial cells. 792 84

We examined changes in fibrinolytic parameters in male patients with diabetes mellitus (DM) and controls. DM patients were divided into three groups: patients without retinopathy, patients with simple retinopathy, and patients with proliferative retinopathy. Plasma levels of t-PA (tissue plasminogen activator) and t-PA-PAI-1 (plasminogen activator inhibitor-1) complex increased with increase in age, but those of PAI-1 (total and free) did not change in controls. On the other hand plasma levels of PAI-1 decreased with increase in age in DM patients. Plasma levels of t-PA, t-PA-PAI-1 complex, free and total PAI-1 increased with increase in body mass index in controls, but no significant changes were shown in these parameters in DM patients. When compared with controls, plasma levels of t-PA, t-PA-PAI-1 complex and PAI-1 were lower in DM patients. Plasma levels of UK (urokinase) and Lp(a) were higher in DM patients. ELT (euglobulin clot lysis time) was significantly shorter in DM patients than in controls. Patients without retinopathy showed increased fibrinolytic activities compared with those with retinopathy due to the increased levels of t-PA in plasma. These results seem to indicate that blood vessels release larger amounts of t-PA at the early stage of DM, then release being impaired at its advance stage. It is also suggested that the regulatory control mechanisms of fibrinolytic activity associated with mechanisms of fibrinolytic activity associated with change in age and body mass index are different between patients with DM and normal people.
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PMID:Changes in fibrinolytic parameters in male patients with type 2 (non-insulin-dependent) diabetes mellitus. 823 67

Complete recanalization was achieved by intra-aortic infusion of urokinase in a case of complete occlusion of the abdominal aorta. The patient was a fifty-nine-year-old man with atrial fibrillation, hypertension, and diabetes mellitus who was admitted because of intermittent claudication and pain in both lower extremities at rest. Angiography demonstrated complete obstruction of the abdominal aorta, but the bilateral iliac arteries were visualized via collaterals. Urokinase was administered intra-aortically in a total dose of 1,200,000 U during the first day and a total dose of 960,000 U during the second day. The aorta and the iliac arteries recanalized after this treatment, and complete recanalization associated with disappearance of subjective symptoms was observed after one month of treatment with warfarin. The present case suggests the usefulness of intra-arterial infusion of urokinase for the treatment of complete occlusion of the abdominal aorta.
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PMID:Complete recanalization of total occlusion in abdominal aorta by intra-aortic infusion of a thrombolytic agent--a case report. 832 87

Phlegmasia cerulea dolens (PCD) is an uncommon, severe form of lower extremity deep venous thrombosis characterized by extremity swelling, cyanosis, and pain. Progression of the thrombotic process may result in extremity gangrene, amputation, and death. The relative value of specific therapeutic regimens in the treatment of this disease remains uncertain. Twelve patients, 9 females and 3 males, with PCD were treated during a 10-year period. Eighteen lower extremities were involved. Pre-existing conditions included malignancy (eight), postoperative state (four), diabetes (three), previous deep venous thrombosis (three), and hypercoagulation (two). Venous gangrene was present in four patients. All patients were treated initially with bedrest, fluid resuscitation, extremity elevation, and systemic high-dose heparin therapy. Five patients had complete resolution with this regimen alone. One patient required cessation of heparin therapy due to heparin-induced thrombocytopenia and developed gangrenous toes. Two patients whose condition failed to respond to heparin therapy underwent catheter-based delivery of urokinase with marked clinical improvement. Four patients, two with venous gangrene, died, three of whom had disseminated malignant disease. A significant percentage of patients with PCD will respond to extremity elevation, fluid resuscitation, and aggressive systemic anticoagulation therapy. Thrombolytic therapy selectively administered is beneficial in patients whose disease fails to respond promptly. Venous thrombectomy should be reserved for patients with contraindications to thrombolysis.
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PMID:Advances in the treatment of phlegmasia cerulea dolens. 835 17

The purpose of this study was to evaluate the efficacy of direct intra-arterial Urokinase infusions prior to anticipated adjunctive reconstructive vascular procedures in 16 patients with 24 acutely or subacutely occluded lower extremity grafts (22 femoropopliteal, 2 femorotibial). Complete thrombolysis was achieved angiographically in 18 (75%) of 24 graft occlusions. Neither age, gender, current smoking, diabetes mellitus, hypertension, nor coronary arterial disease were significantly associated with complete thrombolysis. The only significant factor related to complete thrombolysis was the duration of the occlusion prior to lytic treatment (p < 0.05). Adjunctive reconstructive procedures were performed for eleven of 18 cases in which complete thrombolysis was achieved. These included nine percutaneous transluminal balloon angioplasties (at eight distal and one proximal anastomotic stenoses) and two bypass operations (femoropopliteal). The remaining seven cases had no adjunctive procedure. These 18 cases were examined for patency rates during nine months of follow-up. Six (54%) of 11 cases with adjunctive reconstructive vascular procedures remained patent, while one (14%) of seven cases with no adjunctive procedure remained patent (p = 0.1). Six (25%) of 24 cases resulted in incomplete thrombolysis. Vascular procedures following these cases included two bypass operations, three amputations and one sympathectomy. This study suggests that complete thrombolysis of acutely occluded grafts might have minimized subsequent reconstructive procedures. Identification of correctable lesions and adjunctive reconstructive procedures performed following complete thrombolysis may be the important factors related to long-term patency.
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PMID:Thrombolytic therapy before reconstructive vascular procedures for acute or subacute graft occlusions. 847 85

An 80-year-old man with diabetes developed acute ischemia of the right leg secondary to heparin-induced thrombocytopenia while being treated for a pulmonary embolism. For fear of recurrent thrombosis at the operative site, he was treated with cessation of heparin, placement of a Greenfield filter, and intra-arterial infusion of urokinase into the popliteal artery for 36 hours. All arterial thrombus resolved with no complications. One week later he underwent a below-knee popliteal to anterior tibial artery translocated cephalic vein bypass and transmetatarsal amputation for progressive gangrene of the right toes. The graft remains patent 2 years later. This patient represents the eighth case reported in the world literature in which thrombolytic therapy was used to treat arterial thrombotic complications of heparin-induced thrombocytopenia. Five patients were successfully treated without complications, two others required major amputations, and one died of adrenal hemorrhage. Although thrombolytic therapy should be used cautiously for treatment of arterial thrombotic complications of heparin-induced thrombocytopenia, this adjunct may prove useful and safe in selected cases.
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PMID:Thrombolysis to treat arterial thrombotic complications of heparin-induced thrombocytopenia. 852 43


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