Association between IL-6 and MMP-3 gene polymorphisms and adolescent idiopathic scoliosis: a case-control study.

STUDY DESIGN: Case-control study. OBJECTIVE: As inflammation plays a key role in the etiology of intervertebral disc degeneration, we suggest a possible contribution of pro-inflammatory gene polymorphisms in the pathogenesis of adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: The nucleus pulposus of scoliotic discs responds to exogenous stimuli by secreting interleukin-6 (IL-6) and other inflammatory cytokines. The association between matrix metalloproteinases (MMPs) and disc degeneration has been reported by several investigators. A human MMP-3 promoter 5A/6A gene polymorphism regulates MMP-3 genes expression, while the G/C polymorphism of the promoter region of IL-6 gene influences levels and functional activity of the IL-6 protein. METHODS: We conducted a case-control study to investigate whether the 5A/6A polymorphism of the MMP-3 gene and the G/C polymorphism of the promoter region of IL-6 gene were associated with susceptibility to AIS. RESULTS: The frequency of the 5A/5A genotype of MMP-3 gene polymorphism in patients with scoliosis was almost 3 times higher than in controls (30.2% vs. 11.2%, p 0.001), and the frequency of the G/G genotype of IL-6 gene polymorphism in patients with scoliosis was almost 2 times higher than in controls (52.8% vs. 26.2%, P < 0.001). 5A/5A genotype of MMP-3 gene polymorphism and G/G genotype of IL-6 gene polymorphism are independently associated with a higher risk of scoliosis (odds ratio, respectively, 3.34 and 10.54). CONCLUSION: This is the first study that has evaluated the possibility that gene variants of IL-6 and MMPs might be associated with scoliosis and suggests that MMP-3 and IL-6 promoter polymorphisms constitute important factors for the genetic predisposition to scoliosis.

Reduction of oxidative stress by compression stockings in standing workers.

BACKGROUND: Healthy workers who stand for prolonged periods show enhanced production of reactive oxygen species (ROS) in their systemic circulation. Oxidative stress is thought to be a risk factor for chronic venous insufficiency and other systemic diseases. AIM: To evaluate the effectiveness of compression stockings in the prevention of oxidative stress at work. METHODS: ROS and venous pressure of the lower limbs were measured in 55 theatre nurses who stood in the operating theatre for >6 h, 23 industrial ironers who stood for up to 5 h during their shift and 65 outpatient department nurses and 35 laundry workers who acted as controls. Subjects and controls were examined on two consecutive days before and after work and with and without compression stockings. RESULTS: Without compression stockings, lower limb venous pressure increased significantly after work in all subjects and controls (P < 0.001), while only operating theatre nurses showed significantly higher mean levels of ROS (P < 0.001). There was no significant difference in venous pressures and ROS levels after work in subjects or controls when wearing compression stockings. CONCLUSIONS: Our data suggest a preventive role of compression stockings against oxidative stress in healthy workers with a standing occupation.

Analysis of functional polymorphisms of metalloproteinase genes in persons with vascular dementia and Alzheimer's disease.

BACKGROUND: Vascular dementia (VAD) and Alzheimer's disease (AD) may share common neuropathological mechanisms. Matrix metalloproteinases (MMPs) may induce destruction of the extracellular matrix, neuronal dysfunction, and death. Increased expression of these molecules has been found in a number of neurological diseases, including cerebral ischemia and AD. Expression and activity of MMPs may be genetically influenced by common polymorphisms in the promoter regions of the corresponding genes. The purpose of this study was to evaluate whether functional polymorphisms of MMP genes are associated with dementia. METHODS: This is a cross-sectional study including a total of 599 individuals: 193 with VAD, 183 with AD, and 223 controls. Polymorphisms of the MMP-1, MMP-3, and MMP-9 genes were studied. RESULTS: MMP-1 2G2G, MMP-1 1G2G, MMP-3 5A5A, and MMP-9 TT genotypes were significantly and independently associated with VAD (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.4-4.4, OR = 1.7, 95% CI, 1.0-2.7, OR = 2.9, 95% CI, 1.5-5.9, and OR = 6.8, 95% CI, 1.3-35.1, respectively). MMP-1 2G2G and MMP-3 5A5A genotypes were associated with increased risk of AD only in persons who carry the apolipoprotein E (APOE) epsilon4 allele (OR = 6.0, 95% CI, 2.3-15.5, and OR = 14.3, 95% CI, 3.2-63.0, respectively). Interestingly, the odds of VAD and AD was further increased in persons concomitantly carrying more than one MMP gene variation, compared to individuals that only had one high-risk genotype. CONCLUSIONS: Our study suggests that MMP gene polymorphisms are associated with VAD and AD, although these results need to be treated with caution until replicated. MMP genotypes may influence the risk of dementia and merit further investigation as potential genetic markers of disease.

Interaction between Helicobacter pylori infection and untreated coeliac disease on gastric histological pattern.

OBJECTIVE: Helicobacter pylori infection is the major agent of gastric damage. Coeliac disease may affect the morphology and function of the entire gastrointestinal tract from the stomach to the colon. The aim of this study was to assess the gastric histological pattern in patients with H. pylori and untreated coeliac disease. MATERIAL AND METHODS: We retrospectively enrolled 183 H. pylori-positive patients with (85, group A) and without (98, group B) untreated coeliac disease. The groups were similar for age, gender and smoking habit, and all the patients came from the same geographical area. Histological evaluation of gastric pattern was performed on 4 biopsies (2 in the antrum, 2 in the corpus). Gastric damage was classified according to the modified Sydney System. Diagnosis of H. pylori infection was based on positivity to histology. The chi-square test was used to assess differences between groups. A p-value <0.05 was considered significant. RESULTS: Group A showed a significantly higher prevalence of follicular gastritis than group B (23.5% versus 12.2%, p=0.045). A significantly lower prevalence of atrophic gastritis was observed in group A compared with that in group B (6% versus 22.5%, p=0.002). The prevalence of chronic superficial gastritis, activity degree and intestinal metaplasia was similar between the two groups. CONCLUSIONS: In patients with H. pylori infection, untreated coeliac disease could represent a risk factor for follicular gastritis and is associated with a lower prevalence of atrophic gastritis. The complex interaction between H. pylori and untreated coeliac disease on Th-1/Th-2 balance in the gastric mucosa could explain these results.

Ten-year Echo-Doppler evaluation of forearm circulation following radial artery removal for coronary artery bypass grafting.

OBJECTIVE: To investigate the chronic consequences of radial artery removal for coronary artery bypass surgery on the forearm circulation. METHODS: Thirty-nine patients submitted to radial artery removal for coronary artery bypass were submitted to serial Echo-Doppler evaluation of the flow and morphology of the forearm arteries until 10 years follow-up. RESULTS: The peak systolic velocity of the ulnar artery of the operated side was significantly higher than the control site. The intima-media thickness of the ulnar artery was always significantly higher on the operated side, and this difference reached statistical significance at 10 years follow-up. There was a significantly higher prevalence of atherosclerotic plaques in the ulnar artery (UA) of the operated versus control arm (11/39 vs 0/39; p=0.005). CONCLUSIONS: Radial artery removal for coronary artery bypass surgery leads to a chronic increase in ulnar flow accompanied by increased intima-media thickness and accelerated atherosclerotic disease. These findings may have potentially important implications for surgical indications and patients management.

Idiopathic chronic urticaria and celiac disease.

Idiopathic chronic urticaria (ICU) is a chronic relapsing cutaneous disease. Some case reports or studies on small series of celiac disease (CD) patients have suggested a possible association between CD and ICU. The aim of this study was to assess the prevalence of CD in a population of adults ICU patients with respect to healthy controls. We consecutively enrolled 80 patients affected by ICU and 264 blood donors as the control population without a history of ICU. Serum anti-transglutaminase IgG and anti-endomysium IgA antibodies were evaluated in all subjects. In the case of positivity to serology, diagnosis was confirmed by duodenal biopsy. One of 80 (1.25%) ICU patients were positive to both anti-transglutaminase and anti-endomysium antibodies. Duodenal biopsy showed partial villous atrophy. One control of 264 (0.38%) had CD. No statistical difference was found in the prevalence of CD between the two groups. ICU patients do not seem to bear a greater risk for CD compared to the general population.

Acute cryptogenic liver failure in an untreated coeliac patient: a case report.

Coeliac disease is an autoimmune enteropathy triggered by the ingestion of gluten in susceptible individuals. The clinical presentation of coeliac disease is variable and several extra-intestinal manifestations, as well as an association with autoimmune diseases, have been described. In particular, there are many links between liver disease and coeliac disease. Here we report the case of a young Caucasian woman with acute liver failure, selected as a possible candidate for liver transplantation. Investigation of the patient led to the diagnosis of coeliac disease. A gluten-free diet led to the reversal of the severe liver failure, without the necessity for any surgical or medical treatment.

Chronic compensatory increase in ulnar flow and accelerated atherosclerosis after radial artery removal for coronary artery bypass.

BACKGROUND: Only scant information is available on the chronic consequences of radial artery removal for coronary artery bypass surgery on forearm circulation. METHODS: Twenty-five patients submitted to radial artery removal for coronary artery bypass were submitted to serial Doppler echocardiographic evaluation of the flow and morphology of the forearm arteries. RESULTS: The peak systolic velocity of the ulnar artery of the operated side was significantly higher than that of the control site. The intimal-medial thickness of the ulnar artery was always significantly higher on the operated side, and this difference reached statistical significance at 10 years' follow-up. There was a significantly higher prevalence of atherosclerotic plaques in the ulnar artery of the operated versus control arm (7/25 vs 0/25, P = .03). CONCLUSION: Radial artery removal for coronary artery bypass surgery leads to a chronic increase in ulnar flow accompanied by increased intimal-medial thickness and accelerated atherosclerotic disease. These findings might have potentially important implications for surgical indications and patient management.

Deep venous thrombosis and pulmonary embolism after knee arthroscopy in athletes carrying the thrombophilic factor lupus anticoagulant.

In patients undergoing arthroscopic knee surgery, deep venous thrombosis and pulmonary embolism are rare and there is not clear indication as to the necessity of thromboprophylactic treatment in these patients. However, the role of coagulation disorders in thrombotic events following arthroscopy is unknown. We report 2 cases of massive deep venous thrombosis and pulmonary embolism after knee arthroscopy in athletes carrying the thrombophilic factor lupus anticoagulant, but with no personal or familial history of thrombotic diseases. A few days after the arthroscopic intervention, both patients presented with deep venous thrombosis and 1 developed a severe pulmonary embolism. Blood examination showed that both athletes were lupus anticoagulant-positive. This is the first description of an association between venous thromboembolism, knee arthroscopy, and a prothrombotic condition. This report suggests that screening for hypercoagulability might be useful in athletes undergoing even minimally invasive orthopaedic surgery and that in cases of venous thromboembolism after knee arthroscopy, a prothrombotic disorder should be suspected.

Polymorphisms of the macrophage inhibitory factor and C-reactive protein genes in subjects with Alzheimer's dementia.

Neuroinflammation is a central feature of Alzheimer's disease (AD). C-reactive protein (CRP) is a key molecule of the acute phase of inflammation that has been localized in the two characteristic lesions of AD brain, senile plaque and neurofibrillary tangles. On the other hand, the macrophage migration inhibitory factor (MIF) is a cytokine with multiple biological activities, including the ability to act as potent amyloid beta (A-beta)-binding protein. Two common polymorphisms have been recently detected in the genes encoding for CRP and MIF and have been associated with significant modifications of plasma levels and activity of the corresponding proteins. Following these observations, we hypothesized that CRP and MIF gene polymorphisms might contribute to the development and progression of neurodegenerative disorders and evaluated their association with AD. CRP and MIF gene polymorphisms were examined by polymerase chain reaction and restriction enzyme analysis in 116 Italian subjects affected by probable AD and 184 age- and sex-matched controls. We did not find a statistically significant difference in the distribution of CRP and MIF genotypes and alleles between AD subjects and controls. Although these data need further confirmation, they indicate that CRP and MIF gene polymorphisms are not associated with AD.

Proinflammatory genetic profiles in subjects with history of ischemic stroke.

BACKGROUND AND PURPOSE: Proinflammatory genetic profiles, resulting from the combination of single nucleotide polymorphisms in genes encoding inflammatory molecules, may contribute to the development and progression of cardiovascular diseases. We evaluated the association between history of ischemic stroke and genetic profiles determined by the synergistic effects of polymorphisms in genes encoding prototypical inflammatory proteins. METHODS: The study included 237 individuals with history of ischemic stroke and 223 age-matched and gender-matched controls. The polymorphisms of the C-reactive protein (CRP), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin (E-sel), and matrix metalloproteinase-3 (MMP-3) genes were studied. RESULTS: IL-6 GG, IL-6 GC, MCP-1 GG, ICAM-1 EE, E-sel AA, and MMP-3 5A5A genotypes were significantly and independently associated with stroke history. The odds of stroke increased with the number of high-risk genotypes: carrying 1 proinflammatory gene variant conferred a risk of 3.3 (1.6 to 6.9), whereas individuals concomitantly carrying 2 and 3 proinflammatory gene variants had adjusted odds ratios of 21.0 (7.6 to 57.5) and 50.3 (10.2 to 248.1), respectively. CONCLUSIONS: Proinflammatory genetic profiles are significantly more common in subjects with stroke history. Synergistic effects between proinflammatory genotypes might be potential markers for cerebrovascular diseases.

Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism and risk of Alzheimer's disease in Italians.

Monocyte chemoattractant protein-1 (MCP-1) is a key molecule for monocyte chemotaxis and tissue extravasation and for the modulation of leukocyte function during inflammation. Upregulation of MCP-1 may occur in the brain of subjects affected by Alzheimer's disease (AD) and MCP-1 levels in plasma and cerebrospinal fluid have been proposed as biological markers for the inflammatory process that accompanies AD pathogenesis. Importantly, serum levels and biological activity of MCP-1 protein are strongly influenced by a single nucleotide polymorphism occurring at position -2518 of the MCP-1 gene promoter. A recent study has investigated the possible association between this gene polymorphism and AD in a Spanish population, with negative results. Here, we performed a case-control study to test whether the risk for AD might be influenced by the -2518 A/G polymorphism of the MCP-1 gene in an ethnically homogeneous Italian population. The GG genotype and the G allele of the MCP-1 gene polymorphism were significantly more common in the AD group than in control individuals (P<0.0001) A logistic regression analysis indicated that the GG genotype was an independent risk factor for AD in our population. This effect was not influenced by the presence of the APOE 4 high-risk allele, nor by the presence of other gene variations associated with a pro-inflammatory phenotype. These findings indicate that the -2518 A/G polymorphism of the MCP-1 gene is associated with AD in Italians and confirm that inflammatory gene variations may be important contributors in the development and progression of neurodegenerative disorders.

Treatment of ischemic ulcers of the lower limbs with alprostadil (prostaglandin E1).

BACKGROUND: Hemodynamic, hemorheologic, and metabolic changes are main determinants in the genesis of ischemic leg ulcers. Because prostaglandin E1 (alprostadil) could successfully counteract these changes, it has been intravenously used in the treatment of this disease. OBJECTIVE: The aim of this study was to evaluate the efficacy of alprostadil in the treatment of ischemic ulcers and to compare subcutaneous with intravenous administration. METHODS: Eighty patients were enrolled. Twenty-five were treated by injecting low doses of alprostadil around ischemic ulcers of the leg and saline solution intravenously and 25 were treated with intravenous alprostadil and local injections of saline solution; the control group was composed of 30 patients who received saline solution around the ulcers and intravenously. RESULTS: All patients showed a statistically significant improvement in ulcer diameter, pain, and transcutaneous oxygen pressure compared to the control group. No relevant differences in the clinical outcome in the two treated groups were found, but patients treated with subcutaneous alprostadil experienced no side effects and showed higher values of transcutaneous oxygen pressure. CONCLUSIONS: Both intravenous and local subcutaneous alprostadil are useful in the treatment of ischemic leg ulcers, but subcutaneous administration is less expensive and easier to perform.

The relationship between chronic H. pylori infection, CagA seropositivity and stroke: meta-analysis.

AIMS: There is contrasting evidence on the relevance of chronic infection by Helicobacter pylori (H. pylori) as a risk factor for stroke. We performed a meta-analysis of case-control studies to assess association of H. pylori infection and more virulent H. pylori strains, bearing the cytotoxin-associated gene-A (CagA) antigen, with different types of stroke. METHODS: Outcome measures were: H. pylori and CagA seroprevalence in (1) patients with stroke versus controls, and (2) patients with stroke due to large vessel stroke versus patients with other types of stroke and controls. RESULTS: Seven cross-sectional, case-control studies were included. Odds ratio for individual case-control studies and pooled OR for the association between H. pylori seropositivity and stroke was 1.49 (95% CI 1.24-1.81), for the association between stroke and anti-CagA positivity was 2.23 (95% CI 1.49-3.36). Patients with large vessel stroke had higher odds for H. pylori infection than patients with other types of stroke (odds ratio 1.65; 95% CI 1.12-2.45), and than controls (odds ratio 1.61; 95% CI 1.13-2.32). CONCLUSIONS: Association between H. pylori positivity, anti-CagA positivity and stroke is modest and seems higher with stroke due to large vessel disease. This meta-analysis suggests that the role of CagA positive H. pylori strains in different stroke etiologic subclasses should be the target of future prospective investigation.

CagA-positive cytotoxic H. pylori strains as a link between plaque instability and atherosclerotic stroke.

AIMS: Previous studies suggested an association between infection by cytotoxic CagA-positive Helicobacter pylori strains and atherosclerotic stroke. It has been hypothesized that CagA strains could increase the risk for stroke by affecting carotid plaque irregularity. Our aims were: (1) to confirm the association between CagA strains and atherosclerotic stroke, and (2) to assess the association between CagA strains and carotid plaque irregularity. METHODS AND RESULTS: We enrolled 105 consecutive patients affected by atherosclerotic stroke and 130 sex, age, social background-matched controls without relevant vascular diseases. Risk factors for atherosclerotic stroke, H. pylori infection and CagA status were evaluated in all subjects. The presence of plaque instability was evaluated by colour Doppler ultrasound. The prevalence of CagA-positive strains was significantly higher in patients than in controls (adjusted OR 2.99, 95% CI 1.52-5.88, P=0.002). The CagA seropositivity was the only factor independently associated with carotid plaque irregularity (adjusted OR 8.42, 95% CI 1.58-44.64, P=0.004). CONCLUSION: The evidence of significant associations between CagA-positive H. pylori strains and the presence of carotid plaque instability support their possible involvement in the pathophysiology of atherosclerotic stroke.

Atherosclerotic involvement of the radial artery in patients with coronary artery disease and its relation with midterm radial artery graft patency and endothelial function.

BACKGROUND: The radial artery has recently been proposed as an alternative arterial conduit for surgical myocardial revascularization. This study was conceived to evaluate the degree of atherosclerotic involvement of the radial artery in patients with coronary artery disease and the eventual influence of a subtle degree of preoperative atherosclerosis on the midterm results of radial artery grafts. METHODS AND RESULTS: The intima-media thickness of the radial artery, common carotid artery, and internal thoracic artery was evaluated in 42 coronary artery disease patients and in 26 control patients. All radial arteries were then used for myocardial revascularization; 30 patients submitted to control angiography after 5 years. The mean intima-media thickness was 0.92 +/- 0.22 mm for the common carotid artery, 0.54 +/- 0.16 mm for the internal thoracic artery, 0.55 +/- 0.11 mm for the radial artery in coronary artery disease patients versus 0.79 +/- 0.14 mm, 0.52 +/- 0.11 mm, and 0.56 +/- 0.09 mm, respectively, in control patients (P =.001 only for the common carotid artery). No correlation was found between the intima-media thickness of the carotid, internal thoracic, and radial artery. No correlation was found between the preoperative intima-media thickness of the radial artery and the midterm patency and endothelial-mediated vasodilating capacity of radial artery grafts. CONCLUSION: In coronary artery disease patients, radial artery atherosclerotic involvement is more frequent than that of the gold standard internal thoracic artery but still by far less severe than that of the common carotid artery. The early atherosclerotic signs often observed in the radial artery do not seem to have the potential to influence radial artery graft patency and endothelial function.