Genetic variations of the endothelial nitric oxide synthase gene are related to increased levels of C-reactive protein and macrophage-colony stimulating-factor in patients with coronary artery disease

It was the objective of this study to investigate the relation between nitric oxide synthase (NOS3) gene polymorphisms, vascular inflammation, endothelial function, and atherosclerosis. We examined the effects of a variable nucleotide tandem repeats (VNTR) in intron 4, G894T in exon 7 and T-786C at the promoter region of NOS3 on i) C-reactive protein (CRP) and macrophage-colony stimulating-factor (MCSF), and ii) augmentation index (AI) measured by pulse-wave analysis , flow-mediated dilation (FMD) of the brachial artery, intima-media thickness (IMT) of the carotid and femoral artery using ultrasonography and ankle-brachial index (ABI) in 122 patients with chronic coronary artery disease (CAD) who underwent coronary angiography. MCSF and CRP were increased in patients withT-786C (77/122) or VNTR (40/122) allele compared to those without (F = 10.8, p = 0.002 and F = 3.8, p = 0.04 for T-786C and F = 3.65, p = 0.04 and F = 3.2 p = 0.049 forVNTR), even after adjustment for traditional risk factors and medication. Patients with combination of VNTR and T-786C (31/122) had higher MCSF or CRP than patients with one or none of these alleles (p < 0.05). Among patients with T-786C, those with MCSF>262 pg/ml or CRP>3.2 mg/l (n = 33/77) had a higher femoral and carotid IMT and number of plaques in the peripheral arteries than those with lower values of these inflammatory indices (p < 0.05). Patients with MCSF >262 pg/ml had also lower FMD and higher Gensini score than those with lower MCSF (p < 0.05). The intron 4-VNTR and T-786C mutation of NOS3 gene enhance the inflammatory process in patients with chronic CAD.     

Necrotic vasculitis in a patient with abdominal fibromatosis and Guillain-Barré syndrome

The case of a 65-year-old woman presenting with Guillain-Barré syndrome is herein reported. Tomographic investigation revealed abdominal and retroperitoneal fibromatosis. During her hospitalization, renal involvement ensued, and subsequent renal biopsy demonstrated findings of crescentic pauci-immune glomerulonephritis negative for ANCA antibodies and with characteristics indicative of necrotic angiitis. The simultaneous existence of the three diseases in the same patient as well as the relation between necrotic vasculitis and G-B syndrome is speculated, and the relevant literature is reviewed.     

Victorian orthoptists' performance in the photo evaluation of diabetic retinopathy

PURPOSE: The aim of this study was to investigate the effectiveness of orthoptists in detecting various grades of diabetic retinopathy (DR) and retinal pathology not directly associated with diabetes and to identify factors associated with best performance. METHODS: Forty-five orthoptists completed a survey comprising questions regarding their workplace experiences, plus a photo evaluation task with 36 digital fundus images. RESULTS: We found that orthoptists' overall performance in detecting the presence of abnormality in a series of DR images was high, the mean sensitivity being 86% and specificity 91%. The sensitivity was lower for images with minimal non-proliferative DR, but higher for those with mild-moderate and severe grades of DR. No factors were predictive of performance on the screening task. CONCLUSIONS: Orthoptists performed extremely well, meeting the guidelines for DR screening recommended by National Health and Medical Research Council. The results indicate that orthoptists could potentially be used in DR screening models in Australia.     

IgA anticardiolipin antibody is associated with the extent of daily-life ischaemia in patients with chronic coronary artery disease

Background:

Circulating anticardiolipin antibodies (aCL) may cause endothelial dysfunction. We investigated whether aCL are related to platelet activation, thrombin generation and daily‐life ischaemia in patients with chronic coronary artery disease (CAD).

Methods

We measured (medians 25th–75th percentile) IgG, IgM, IgA aCL serum levels (Arbitrary Elisa Units, AEU), prothrombin fragments (F1+2, nmol/l), 24 h urine excretion of 11‐dehydrothromboxane B2 (11‐DHTXB2, ng/mg creatinine) creatine kinase (CK) and its cardiac isoenzyme CK‐MB (IU/l) in 60 patients with angiographically documented CAD and in 40 age and sex matched controls. Patients underwent a 48 h Holter monitoring for assessment of the number and duration of ischaemic episodes.

Results

Patients had higher IgA‐aCL levels than controls (3.2 vs 2.4 AEU, p = 0.002). Increased IgA‐ACA levels were related to increased number and duration of ischaemic episodes (p<0.01). By ANOVA, patients with ⩾10 ischaemic episodes (3rd tertile) or duration of ischaemia ⩾32min (3rd tertile) had higher IgA‐aCL than those with lower ischaemic burden (4.95 vs 3 vs 2.5 AEU, p = 0.002 and 4.9 vs 3 vs 2.5 AEU, p = 0.001 respectively). Patients with ⩾2 ischaemic episodes (2nd and 3rd tertile) had higher 11‐DHTXB2, than those with minimal ischaemia (2< episodes, 1st tertile) (p = 0.001). CK and CK‐MB were within normal range after Holter monitoring. Receiver operating curve analysis showed a greater area under the curve for IgA‐aCL than for 11‐DHTXB2 in predicting severe ischaemia (⩾10 ischemic episodes or ⩾32 min duration of ischaemia).

Conclusion

Increasing IgA‐aCL levels are associated with increasing ischemic burden in patients with CAD.While cardiac enzymes are sensitive markers of myocardial necrosis, there are no reliable biomarkers for myocardial ischaemia. Increased production of anticardiolipin antibodies (aCL) has been linked to lipid peroxidation and may cause endothelial dysfunction favouring vasoconstriction.¹ In this study we examined the relationship between aCL, platelet activation and ischaemia during daily‐life activities as assessed by 48 h Holter monitoring in chronic coronary artery disease (CAD).     

The effect of acute administration of statins on coronary microcirculation during the pre-revascularization period in patients with myocardial infraction

The beneficial effects of statin pretreatment as well as of staccato reperfusion (SR) on myocardium have been demonstrated in patients undergoing cardiac interventions. In this study, we compared the effects of the acute statin administration prior to percutaneous coronary intervention (PCI) with the effects of staccato or abrupt reperfusion on coronary microcirculation in patients with myocardial infarction (MI).MethodsWe randomly assigned 47 patients who had ST-elevation or non-ST-elevation MI 48 h prior to PCI, into three groups: staccato reperfusion (consisting of 6 periods of 10-s balloon inflation/deflation) plus statin therapy (SRSG), statin therapy plus abrupt reperfusion (SG), and abrupt reperfusion alone (ARG). Myocardial contrast echocardiography (MCE) was performed to assess the blood volume (A), velocity (β) and flow (A × β) of the segments associated with the PCI-treated artery the day following intervention and 30 days after. LV end-diastolic (EDV) and systolic volumes (ESVs), wall motion score index (WMSI) were evaluated.ResultsCompared to ARG, SRSG and SG resulted in a greater improvement in A, β and A × β (F = 20.6, p < 0.001 for A, F = 3.5, p = 0.03 for β and F = 11.3, p < 0.001 for A × β for the overall effect of intervention) as well as a greater decrease of WMSI, EDV and ESV (p < 0.01) one month post-PCI. The changes of all echocardiography markers were greater in SRSG than SG (p < 0.01). The % changes in ESV correlated with the corresponding % changes in MCE indices in SRSG and SG (p < 0.05).ConclusionThe acute statin administration prior to reperfusion either alone or in synergy with staccato reperfusion ameliorates coronary microcirculatory dysfunction in patients with myocardial infarction     

Treatment with granulocyte colony stimulating factor is associated with improvement in endothelial function

Primary objective: Granulocyte-colony stimulating factor (G-CSF) is used for the mobilization of bone marrow and endothelial progenitor cells, though G-CSF-induced inflammation may cause endothelial dysfunction. We examined the effects of G-CSF on endothelium, C-reactive protein (CRP), tumour necrosis factor-α (TNF-α) and anti-inflammatory cytokines namely interleukin 10 (IL-10).

Research design: We studied 60 women with breast cancer, who were randomized to either subcutaneous G-CSF (5 μg/kg), o.d. for 5 days after adjuvant chemotherapy (n = 40) or placebo (n = 20).

Experimental interventions: We measured flow-mediated dilatation (FMD%) of the brachial artery by ultrasonography, CRP, TNF-α, IL-10 and the ratio TNF-α/ IL-10 blood levels before, 2-h and 5-days after the G-CSF or placebo treatment.

Main outcomes and results: There was a greater increase of FMD, IL-10 and reduction of TNF-α/ IL-10, 2 h and 5 days after the G-CSF treatment compared to placebo. Although, CRP and TNF-α were higher, TNF-α/IL-10 was lower at the end of G-CSF treatment compared to placebo. Improvement of FMD was related to changes of IL-10 and TNF-α/IL-10.

Conclusions: Treatment with G-CSF improves endothelial function in vivo, possibly by shifting the balance between the pro- and anti-inflammatory cytokines.