Conservative treatment of patients with thromboangiitis obliterans or cannabis-associated arteritis presenting with critical lower limb ischaemia.

BACKGROUND: Proper management of patients with thromboangiitis obliterans (TAO) or cannabis-associated arteritis (CAA), presenting with critical lower limb ischaemia (CLI) remains controversial, and data are limited. PATIENTS AND METHODS: Patients with TAO or CAA presenting with CLI between 2011 and 2016 were retrospectively evaluated. Patients requiring primary intervention were excluded. Conservative treatment included: (a) weight-adjusted bemiparin plus six hours/day intravenous iloprost for 28 days, (b) aspirin (100 mg/day) plus cilostazol (100 mg twice/day) after discharge, and (c) strict recommendations/monitoring for smoking cessation. Main outcomes included symptom recession, ankle-brachial index (ABI) improvement, and healing of lesions at the time of discharge as well as amputation, revascularization, and abstinence rate during follow-up. RESULTS: Overall, 23 patients (TAO: 15; CAA: 8) were included within six years, none of the patients reported any other factor than smoking. All patients presented with rest pain and 12 patients with ulcer or necrotic lesions. Mean ABI measurement at presentation was 0.46 ± 0.2, after 28 days of treatment, all patients showed improvement regarding clinical picture and ABI measurement (0.54 ± 0.1; p < 0.05). During follow-up, only three patients underwent bypass surgery and two patients underwent major amputation, although the smoking abstinence rate was very low (13 %). CONCLUSIONS: Intravenous iloprost plus bemiparin for 28 days together with per os aspirin plus cilostazol seem to produce promising results in patients with TAO/CAA, treated for CLI, even with a low smoking abstinence rate. However, larger series are needed to further evaluate inter-group differences and potential prognostic factors.

Cannabis arteritis.

Cannabis is the most consumed psychoactive substance by young people. Chronic use of cannabis can lead to cannabis arteritis, which is a very rare peripheral vascular disease similar to Buerger's disease. It is affecting young adults, especially men, consuming cannabis. A 27-year old woman, with no particular past medical history except for long-term use of cannabis and tobacco developed a digital necrosis in the left hand. She denied using other illicit drugs. Doppler ultrasound examination of the upper limbs was unremarkable. Toxicological analysis revealed the presence of cannabis in both biological fluid and hair strand. Despite medical treatment, cessation of the cannabis and tobacco consumption and hyperbaric oxygen therapy, an amputation of necrotic parts was then required. This case shows the prolonged use of cannabis could be a risk factor for young adult arteritis. Faced with a rapidly progressive arteritis occurring in young adult, the physician should consider the history of use of cannabis. Hair analysis can be useful for confirmation of the chronic consumption of drugs.

Effect of long-term homocysteine reduction with B vitamins on arterial wall inflammation assessed by fluorodeoxyglucose positron emission tomography: a randomised double-blind, placebo-controlled trial.

BACKGROUND: Homocysteine may promote atherosclerosis by exacerbating inflammatory processes within the arterial wall. B-vitamin supplements reduce total plasma homocysteine concentrations (tHcy), but it is not known whether the treatment also reduces arterial wall inflammation. We used (18)F-fluorodeoxygluose positron emission tomography ((18)F-FDG PET) to investigate whether long-term homocysteine-lowering treatment alters arterial wall inflammation in patients with a history of ischemic stroke. METHODS: 30 stroke patients were randomly assigned to B-vitamin therapy (folic acid 2 mg, vitamin B(6) 25 mg and vitamin B(12) 0.5 mg) or placebo in a double-blind clinical trial. After a mean treatment period of 4.0 +/- 0.7 years, all subjects had tHcy, carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) of the brachial artery measured and underwent an (18)F-FDG PET scan. Standardised uptake values (SUV) were measured at six sites in the carotid, femoral and aortic arteries. Areas of locally increased tracer uptake in the arterial wall ('hot spots') were also identified and counted. RESULTS: Long-term B-vitamin treatment significantly reduced tHcy compared with placebo (8.4 micromol/l, 95% confidence interval, CI, 7.2-9.6 vs. 11.6 micromol/l, 95% CI 10.0-13.4, p = 0.002). The treatment did not affect mean arterial SUV (2.0 +/- 0.3 vitamins vs. 2.1 +/- 0.3 placebo, p = 0.65) or the number of hot spots (n = 1.1 +/- 1.0 vitamins vs. n = 1.2 +/- 1.0 placebo, p = 0.65). There was no significant correlation between mean arterial SUV and CIMT or FMD. CONCLUSIONS: These results suggest that a long-term Hcy reduction with B vitamins does not affect arterial wall inflammation assessed by (18)F-FDG PET.

Dysregulated RANK ligand/RANK axis in hyperhomocysteinemic subjects: effect of treatment with B-vitamins.

BACKGROUND AND PURPOSE: Homocysteine has been linked to increased risk of ischemic stroke and other cardiovascular events. Matrix degradation and inflammation play an important role in these disorders, and we have demonstrated increased levels of matrix-degrading enzymes and inflammatory cytokines in hyperhomocysteinemic individuals. Recent studies suggest that RANK ligand (RANKL) through interaction with its receptor RANK can modulate matrix degradation and inflammation. The present study aimed to examine the role of the RANKL/RANK axis in hyperhomocystinemia. METHODS: RANKL/RANK was measured on protein or mRNA level before and after B-vitamin supplementation in hyperhomocysteinemic individuals. We also examined the in vitro effects of soluble RANKL in peripheral blood mononuclear cells from hyperhomocysteinemic individuals. RESULTS: Our main findings were: (1) compared to peripheral blood mononuclear cells from controls, cells from hyperhomocysteinemic individuals had significantly higher gene expression of RANKL and RANK; (2) folic acid treatment for 6 weeks in an open, uncontrolled study significantly reduced gene expression of RANKL/RANK in peripheral blood mononuclear cells from these individuals; (3) compared to placebo, treatment with folic acid, vitamin B(12), and vitamin B(6) for 3 months in a randomized, double-blind trial significantly lowered serum levels of soluble RANKL in hyperhomocysteinemic individuals; and (4) in vitro, soluble RANKL markedly increased the release of matrix metalloproteinase-9 and inflammatory cytokines from peripheral blood mononuclear cells in hyperhomocysteinemic subjects. CONCLUSIONS: Our findings suggest a dysregulated RANKL/RANK axis in hyperhomocysteinemic subjects. Based on their role in atherogenesis, this enhanced expression of RANKL and RANK could contribute to the increased risk of cardiovascular disease in hyperhomocystinemia. Moreover, treatment with B-vitamins may have beneficial implications for plaque stability in these individuals.

Scutellarin isolated from Erigeron multiradiatus inhibits high glucose-mediated vascular inflammation.

Erigeron multiradiatus (Lindl.) Benth is a traditional Tibetan medicine herb long used to treat various diseases related to inflammation. Our previous phytochemical studies on E. multiradiatus resulted in the isolation of scutellarin, which is a known flavone glucuronide with comprehensive pharmacological actions. In present study, we investigated the inhibition action of scutellarin on high glucose-induced vascular inflammation in human endothelial cells (ECV304 cells). Consistent with previous reports, exposure of ECV304 cells to high glucose for 24 h caused an increase of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1), and promoted cell adhesion between monocyte and ECV304 cells. However, pretreatment with scutellarin (0.1 and 1 microM) reversed these effects in a concentration-dependent manner. Scutellarin was able to inhibit the activation of NF-kappaB induced by high glucose in ECV304 cells. Furthermore, although oral administration of scutellarin (10 and 50 mg/kg) did not produce significant antihyperglycemic action, it lowered the serum MCP-1 levels significantly in alloxan-induced diabetic mice. Therefore, our results suggest that scutellarin has anti-inflammation effect that may afford some protection against hyperglycemia-induced vascular inflammatory both in vitro and in vivo.

Multiple occlusive retinal arteritis in both eyes of a patient with rheumatoid arthritis.

PURPOSE: To report multiple occlusive retinal arteritis as a complication of rheumatoid arthritis. CASE: A 67-year-old woman developed superotemporal branch retinal artery occlusion in both eyes, together with arterial sheathing and large cotton wool patches around the optic disc, in the course of rheumatoid arthritis with moderate activity. OBSERVATIONS: Fluorescein angiography disclosed delayed filling of the superotemporal retinal artery in the right eye and no filling of the superotemporal artery in the left eye. In addition, segmental absence of filling was found in peripheral branches of the other major retinal arteries in both eyes. After hyperbaric oxygen therapy and intravenous administration of prostaglandin E1 and urokinase for 2 weeks, there was improvement in her vision. CONCLUSION: Multiple occlusive retinal arteritis in rheumatoid arthritis can manifest as retinal artery occlusion. Rheumatoid arthritis should be included in the differential diagnosis of bilateral retinal artery occlusion.

Suppression of coronary vasculitis in a murine model of Kawasaki disease using an angiogenesis inhibitor.

Coronary arteritis can be induced in C57BL/6 mice with a single intraperitoneal (ip) injection of Lactobacillus casei cell fragments. Histologic sections resemble the vasculitis and aneurysms observed in the medium-sized coronary arteries of children with Kawasaki disease. Since endothelial cells could play an important role in the development of vasculitis, a recently described angiogenesis inhibitor that is not an immunosuppressive agent, AGM-1470 (derived from Aspergillus fumigatus), was used to evaluate its therapeutic potential in this model. A total of 32 mice were administered 0.5 mg of sterile L. casei preparation ip on day 0 and randomized to either a treatment (AGM-1470, 27mg/kg sc alternate days) or a control (vehicle only) protocol. Hearts were harvested on day 14 (early disease) or at the end of the study on day 28 (established disease). Histologic sections were scored blindly for vasculitis. Day 14 sections from both protocols manifested only minimal disease, indicating that the vasculitis had not yet matured. By day 28, the AGM-1470 group had significantly less coronary vasculitis than the control group (0.7 vs 2.6, p < 0.005, respectively). These studies suggest that endothelial cells may play an active role in this pathologic process and that angiogenesis inhibitors, such as AGM-1470, could be useful tools for the treatment and understanding of vasculitis.

Ginseng-associated cerebral arteritis.

We report a 28-year-old woman who had a severe headache after ingesting a large quantity of ethanol-extracted ginseng. Cerebral angiograms showed "beading" appearance in the anterior and posterior cerebral and superior cerebellar arteries, consistent with cerebral arteritis. The close temporal association between intake of ginseng and cerebral arteries suggests a causal relationship.

[Disorders of the blood circulation in the gastrointestinal tract]. / Durchblutungsstörungen am Gastrointestinaltrakt

Blood flow disturbances in the gastrointestinal tract can lead to serious illness. They can be acute or chronic, their cause may be arterial or venous occlusion or hypotonia. Lesions of the gastrointestinal tract caused by ischemia depend on localisation, acuteness and degree of the blood flow disturbance. They may reach from focal and segmental ischemic lesions to extensive necroses of the entire intestinal tubes. The most serious ischemic disease is the embolic and thrombotic occlusion of the arteria mesenterica superior due to previous arterosclerotic damage. Infarction of a large part of the intestines and peritonitis can be the consequence. These patients' only chance of survival is early diagnosis--as a rule exclusively via angiography--and immediate surgery. Chronic occlusion of the arteria mesenterica superior leads to angina abdominalis which mainly occurs after food intake and can last for hours. The reason may also be a general arteriosclerosis. Men are affected more frequently and at a younger age than women. As a consequence of lowered intestinal blood flow these patients suffer from malabsorption and heavy weight loss. Conservative therapy is not effective. These patients, too, will have to be treated surgically after previous angiography. Vascular disease with decreased blood flow as its consequence can be found in a number of inflammatory diseases, in malign hypertensian, in collagen disease and in other more rare diseases as pseudoxanthoma elasticum or Ehlers-Danlos-syndrome. In the case of ischemic colitis arterial and more rarely venous occlusions cause decreased blood flow in the big bowel. A frequent consequence is colitis in the left colon which is characterized by acuteness, pain in the left side of the abdomen and by heavy rectal bleeding. Diagnosis is established by means of endoscopy, barium enema and angiography. Primarily therapy of ischemic colitis is of the conservative type. In severe cases with gangrene and peritonitis the colon has to be resected.