Hyperhomocysteinaemia and endothelial dysfunction in peripheral arterial disease.
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Biomedical subjects
Publications and source records attributed to C Conri.
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Hyperhomocysteinaemia has been associated with arterial and venous thrombosis possibly by causing damage to the endothelium. We hypothesised that an oral load in methionine, that increases plasma homocysteine, would also result in an increase in biological markers of endothelial or platelet dysfunction. Then we investigated two groups of patients with arterial or venous occlusive disease: 17 with hyperhomocysteinemia and 12 without hyperhomocysteinemia. We measured in both groups plasma soluble thrombomodulin, von Willebrand factor, P-selectin and tissue factor plasma inhibitor before and 6 hours after a load with 100 mg/kg oral methionine. Methionine load resulted in a significant increase in von Willebrand factor in both groups (P<0.02), suggesting that endothelial dysfunction occurs during the load.
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PURPOSE: Aortoduodenal fistulas are the most frequent aortoenteric fistulas. They may be primary (occurring after aneurysms of the native aorta) or secondary (occurring after aortic prosthesis). Aortoduodenal fistulas are a rare complication of aortic prostheses. They may be caused by prosthesis infection or due to inadequate prosthesis. METHODS: We report seven observations that emphasize issues pertaining to either diagnosis or therapy. RESULTS: The delay of occurrence is variable, with a mean of 3 years as reported in the literature. Clinical picture includes upper digestive tract hemorrhage, sometimes fever, abdominal pain or mass. Though difficult, diagnosis can be achieved through gastric endoscopy or CT-scan. Additional diagnostic procedures are often not useful and should not be numerous. Surgical procedures help guide the diagnosis and constitute the main part of the treatment with suture of the duodenum and vascular prosthesis. According to previous works, our observations including prolonged follow-up of the patients suggest that the best vascular treatment is extra-anatomic axillo-bifemoral bypass, while simple suture and prosthesis replacement lead to poor results. CONCLUSION: Mortality related to aortodigestive fistulas is high (five out of seven patients in the present study) and requires prevention, including more particularly delicate surgery and antibiotic therapy in case of any episode of infection. Aortoduodenal fistulas must be suspected whenever a patient with aortic prosthesis has digestive bleeding or unexplained fever.
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Hyperhomocysteinaemia is a risk factor for premature atherosclerosis and venous thromboembolic disease. Supplementation with folic acid and vitamin B6 has been shown to decrease plasma homocysteine but data fail to assess an effect on the progression of vascular disease. We measured plasma homocysteine and two markers of endothelial injury (plasma soluble thrombomodulin and von Willebrand factor) at baseline and after 3 months of treatment with folic acid and vitamin B6. After this treatment there was a significant decrease in fasting soluble thrombomodulin (-15 ng/ml, 95%CI 5-22.2). Von Willebrand factor was significantly raised after methionine load at baseline but did not significantly rise after supplementation.
We report 6 cases of upper limb involvement in giant cell arteritis; upper limb involvement revealed the disease in 4 cases and clinical symptoms were present in 5 (upper limb pain, Raynaud's phenomenon). Upper limb pulses were not palpable and blood pressure unmeasurable in all. Duplex ultrasonography found signs of inflammatory arteriopathy in 4 cases (hypoechogenous halo of the arterial wall and acceleration of flow velocity). Arteriography was performed in 5 cases and showed long and regular stenoses. In the last case, arteriography was not done because the duplex exploration gave an easier diagnosis. With this technique, the diagnosis of upper limb involvement, frequent in autopsy series of giant cell arteritis, might be made more often. Corticosteroid therapy is indicated and surgery should be discussed only in emergency situations.
Hemorrhagic complications are the most frequent complications of antivitamin K (AVK) treatments and can be life-threatening. We report 75 patients from a University Hospital. They were 40 males and 35 females (median age 74 years, 20-94), and were classified into 3 grades according to clinical picture: grade 1 (no surgery or transfusion, grade 2: surgery or blood transfusion needed, grade 3: death). 43 patients had grade 1 complications, 27 grade 2, and 5 grade 3 complications. The most frequent complications were muscular hematomas (36 patients), sub-cutaneous hematomas (14 patients), digestive bleeding (13 patients), hematuria (12 subjects). Eight patients had intracerebral bleeding, of whom 3 died. The treatment time was very variable (1 to 988 weeks). Only half patients had a prothrombin rate (PR) below 20% but two thirds had an INR above 5. This study showed that PR was a poor predictor of hemorrhagic complications. INR was a better parameter. For 15 patients, we considered that the indication was unadapted or questionable, among whom 2 died. This work suggests that the promotion of AVK prescription rules should go on.
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INTRODUCTION: Familial auto-immune hepatitis is unusual. We report a case in which hepatitis was associated with a deficiency in the C4 component of the complement. EXEGESIS: Type 1 auto-immune hepatitis A was diagnosed in a 38-year-old woman presenting with systemic lupus erythematosus. Her daughter had to undergo a splenectomy for immunologic thrombocytopenic purpura when she was 9 years old. When she turned 13, she further developed type 1 autoimmune hepatitis. During follow-up (4 and 8 years, respectively), both patients had a mild deficiency in C4. CONCLUSION: C4 deficiency is not only frequently observed in relatives of patients with auto-immune hepatitis, but also in familial systemic lupus. This abnormality may have had a crucial pathogenic role in these two patients.
INTRODUCTION: Some viral infections are associated with deep venous thrombosis. We report a case of deep venous thrombosis in an adult with varicella. He had neither known predisposing factors for thrombosis nor thrombophilia. EXEGESIS: Transient significant level of antiphospholipid antibodies and lupus circulating anticoagulant were observed. There was no evidence of thrombophilia. Deep venous thrombosis has been mostly associated with varicella in children. A transient protein S deficiency was present in almost all cases, though it was sometimes related to an anti-protein S antibody. This association is exceptional in adults. Some viruses such as herpesvirus and HIV are responsible for endothelium dysfunction, but this is still unclear in the case of varicella-zoster virus. CONCLUSION: In our observation, endothelium activation or antiphospholipid antibodies might be responsible for thrombosis.
BACKGROUND: We investigated the possible role of antiphospholipid (APA) and anti-human 2-glycoprotein I (beta2-GPI) antibodies (Ab) in thrombosis and atherosclerosis in human immunodeficiency (HIV)-positive patients, in whom they seem to be more frequent. METHODS: We measured APA and anti-beta2-GPI Ab in 58 HIV-positive patients together with markers of disease progression, circulating beta2-GPI, plasma lipids, biological markers of endothelial activation and integrity (plasma thrombomodulin, von Willebrand factor, vascular cell adhesion molecule 1) and with antimalonic dialdehyde antibodies (anti-MDA Ab). RESULTS: We found a 41% frequency of IgG APA in the HIV-positive patients. APA IgMs were rarely positive (7%), and anti-beta2-GPI IgGs were positive in 3-4% patients. There was no correlation between APA or anti-beta2-GPI Ab and the presence of opportunistic infections. Although plasma thrombomodulin, von Willebrand factor and vascular cell adhesion molecule 1 were significantly increased in the HIV-positive patients, APA was correlated only with vascular cell adhesion molecule 1, suggesting that APAs are correlated with endothelial activation but not with vascular endothelial lesions. A correlation between APA and anti-MDA IgG was demonstrated using multivariate analysis (r=0.542, P < 0.0001), suggesting a relationship between the targets of these antibodies. Finally, IgG APAs are frequent in HIV infection but are not correlated with biological markers of endothelial injury. CONCLUSION: Our results do not support a role for APA or anti-beta2-GPI in HIV-associated silent vascular endothelial damage. However, the role of these autoantibodies in clinically relevant thrombotic events should be investigated in HIV-positive patients.
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Amoebic abscess of the liver is sometimes complicated by deep venous thrombosis but extension to the right atrium is rarely observed. The authors report the case of inferior vena caval thrombosis extending to the right atrium in a case of amoebic hepatic abscess. The patient was treated initially by antibiotherapy with metronidazole associated with intravenous anticoagulation. Rapid extension of the thrombus despite this treatment led to the initiation of thrombolysis. There were no embolic complications and the outcome was good. Apart from the rarity of this complication, this case poses the problem of the management of these patients. No previous reports of the use of thrombolysis were found in the medical literature. In the light of previous publications and the present case, the authors suggest investigation by CT scanning, echocardiography and venous Doppler ultrasonography in all cases of hepatic amoebic abscess.
We report a series of seven patients who had scleroderma renal crisis. Their primary clinical and laboratory features along with the details of their management were compared with those of similar cases from the literature. The seven patients died within one to four months of the diagnosis with a pattern of acute renal failure, left ventricular failure and malignant hypertension. Histopathologic examination was performed in four of the patients, in two of whom it revealed thickening of the wall of the interlobular arteries related to the scleroderma, and in the other two patients nonspecific lesions of malignant hypertension. This histopathologic particularity led us to propose, on the basis of multiple renal biopsies performed in patients with scleroderma, a lesion chronology of the kidney in patients with scleroderma. Nevertheless, the triggering factors and pathophysiologic mechanisms of scleroderma renal crisis remain unclear and its prognosis is severe. Early treatment with angiotensin-converting enzyme inhibitors and other vasodilatators administered intravenously can prevent death and dialysis.
Patients infected with HIV are at increased risk of atherosclerosis, and have evidence of endothelium dysfunction. The hypothesis was tested that HIV-related endothelium dysfunction is related to loss of antioxidants. This was done by the supplementation of the antioxidants selenium and beta-carotene. We supplemented the diet of 10 HIV-seropositive subjects with 100 microg selenium daily, 11 subjects with 30 mg beta-carotene twice daily while 15 subjects were not supplemented. Plasma was obtained at outset and after a year, and tested by ELISA for endothelial cell, platelet and inflammatory markers. The non-supplemented patients experienced increases in von Willebrand factor and soluble thrombomodulin (both p <0.01). There were no changes in any of the indices in the patients taking selenium or beta-carotene. Increased von Willebrand factor and soluble thrombomodulin in the non-supplemented patients imply increased damage to the endothelium over the year of the study. Therefore we interpret the lack of increase in the patients taking antioxidants as evidence of the protection of the endothelium by these agents.
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