Coagulation factor XIII Val34Leu gene polymorphism and Alzheimer's disease.

Blood coagulation factor XIII (FXIII) plays a role in inflammatory processes and a pathogenetic role of inflammation in neurodegenerative disorders has been proposed. FXIIIa subunit was immunohistochemically detected in a subpopulation of reactive microglia in Alzheimer's disease (AD). Aim of the present study is to evaluate whether a common polymorphism of the FXIII gene is associated with sporadic AD. We examined 90 patients affected by sporadic AD and 139 age- and sex-matched controls to assess the distribution of V/L alleles and genotypes of the FXIIIa-subunit gene. The LL genotype showed a significantly higher frequency in AD patients (p<0.05) with a significantly increased risk of AD in the presence of LL genotype at the logistic regression analysis [odds ratio: 3.6 (1.36-9.44), p<0.01]. This study shows for the first time an association between FXIII Val34Leu polymorphism and AD.

The K469E polymorphism of the ICAM-1 gene is a risk factor for peripheral arterial occlusive disease.

Intercellular adhesion molecule-1 (ICAM-1) plays a crucial role in lymphocyte migration and activation, and is considered important in the pathogenesis of atherosclerosis. K469E is a common polymorphism of the ICAM-1 gene with potential functional significance. The aim of the present case-control study was to evaluate the association between this polymorphism and peripheral arterial occlusive disease (PAOD). ICAM-1 gene polymorphism was examined by polymerase chain reaction and restriction enzyme analysis in 75 Italian subjects affected by PAOD and 227 controls. The distribution of ICAM-1 genotypes in patients affected by PAOD was 32.1% EE, 50.6% EK, and 17.3% KK. The distribution of ICAM-1 genotypes in control subjects was 17.2% EE, 55.1% EK, and 27.7% KK. The EE genotype was significantly more common in patients than controls (P = 0.006). Logistic regression analysis indicated that the presence of the EE genotype significantly increases the risk of PAOD (odds ratio, 3.5; 95% confidence interval, 1.5-8.4; P = 0.004). This is the first study documenting a role of the ICAM-1 gene polymorphism in the pathogenesis of a cardiovascular disease, such as PAOD. Our data support the hypothesis that inflammatory mechanisms are important in the pathophysiology of vascular diseases with an atherosclerotic basis.

[An effective method to prevent deep venous thrombosis in total hip arthroplasty: a study in patients with and without risk factors for thrombotic disease]. / Efficacia della profilassi della trombosi venosa profonda nell'artroprotesi totale d'anca. Studio di pazienti con e senza fattori di rischio aggiuntivi.

PURPOSE: The aim of this study was to determine a safe and effective method of prophylaxis for thromboembolis diseases after THA. MATERIALS AND METHODS: This study was conducted on 157 patients consecutively admitted to our Department of Orthopedics to undergo elective THA from October 2000 o May 2001. We have preoperatively investigated plasma levels of homocysteine, AT III activity, Fibrinogen levels, Anticardiolipin antibodies, and circulating vWFag D-dimer levels were measured by Asserachrom D-dimer ELISA preoperatively and on day 4 postoperatively. Thromboprophylactic regimen was based on a prolonged subcutaneous administration of nadroparin (for 40 days after surgery) and was used in all patients, with a dose based on body weight. Compression ultrasonography was udes as screening test for the diagnosis of deep venous thrombosis and performed in each patient on postoperative day 4, 15, and 30. RESULTS: Although all patients enrolled in this study showed increased risk for thrombotic disease, none oh them developed either symptomatic or asymptomatic deep venous thrombosis. No complications were observed, including major bleeding or abnormalities of laboratory tests. CONCLUSIONS: Our study indicates that prolonged thromboprophylaxis with nadroparin for 40 days postoperatively, associated with early mobilization, is an effective and safe protocol of antithrombotic prophylaxis in patients operated for THA with and without risk factors for thrombotic disease.

Local infusion of norepinephrine reduces blood losses and need of transfusion in total knee arthroplasty.

Blood loss after total knee arthroplasty (TKA) is often associated with cardiovascular complications and a high transfusion rate of allogenic blood. In our study we focused our attention on developing a new intra-surgical procedure that appears safe, easy to perform and effective in the reduction of bleeding in TKA. We evaluated 84 patients who underwent TKA and met our inclusion criteria; they were assigned to two groups: 55 controls in which a saline solution was used to wash the surgical field before tourniquet release, and a second group of 29 patients, in which a saline solution containing a low dose of norepinephrine was locally applied before tourniquet release. The local administration of a low dose of norepinephrine has induced a significant reduction of perioperative blood loss and blood transfusion requirements; in addition, this method was characterised by the absence of complications or adverse effects. In conclusion, our data suggest that intraoperative local administration of a low dose of norepinephrine could represent an effective and safe method of reducing blood loss and preventing blood transfusions in patients with TKA.

Interleukin-6 gene polymorphism and risk of osteoarthritis of the hip: a case-control study.

OBJECTIVES: Osteoarthritis (OA) is considered a polygenic disease controlled by the expression of genetic factors. Genes encoding for cytokines have been associated with susceptibility for joint OA and interleukin (IL)-6 gene is also supposed to be involved in the cartilage degradation process. In this case-control study, we evaluated for the first time whether the risk of hip OA might be influenced by the -174 IL-6 gene polymorphism. METHODS: The distribution of IL-6 genotypes was evaluated in 75 patients affected by hip OA and in 107 age- and sex-matched controls. RESULTS: The distribution of IL-6 genotypes in (1) patients with hip OA: 33 GG, 30 GC, 12 CC and (2) control subjects: 34 GG, 40 GC, 33 CC. The frequency of the CC genotype was significantly higher in control patients (P=0.02). Logistic regression analysis indicated that the presence of the CC genotype is independently associated with a decreased risk of OA (odds ratio 0.4 [95% confidence interval 0.1-0.9], P=0.04). CONCLUSIONS: Primary OA of the hip has an important genetic component and variations of genes encoding for inflammatory cytokines, such as IL-6, may play an important role in the series of events responsible for the pathophysiology of OA.

The -174 G/C polymorphism of the interleukin-6 gene promoter is associated with peripheral artery occlusive disease.

OBJECTIVE AND DESIGN: high plasma levels of Interleukin-6 (IL-6) are found in patients with atherosclerotic disorders. Recently, a common polymorphism of the IL-6 gene promoter, influencing the transcription rate of the gene, has been described and associated with atherosclerosis of carotid and coronary arteries. The objective of this study was to test whether IL-6 gene promoter polymorphism is associated with peripheral artery occlusive disease (PAOD) in a case-control study. METHODS: IL-6 gene promoter polymorphism was evaluated by polymerase chain reaction followed by restriction enzyme analysis in 84 patients affected by PAOD and 183 controls. RESULTS: the distribution of IL-6 genotypes was: patients with PAOD: 44 GG, 30 GC, 10 CC; control subjects: 53 GG, 80 GC, 50 CC. The GG genotype was significantly more common in the PAOD group (p<0.0001), while the CC genotype was significantly more common in control patients (p=0.005). CONCLUSIONS: this study indicates a strong association between IL-6 gene polymorphism and PAOD and support the hypothesis that IL-6 and IL-6 gene polymorphism are important in the pathophysiology and evolution of ischaemic diseases of the lower limbs.