Roberto Antonio Flore

Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development.

BACKGROUND/AIMS Prognostic scores currently used in cirrhotic patients do not include thrombotic risk factors (TRFs). Predicting factors of portal vein thrombosis (PVT) development are still unknown. We wanted to describe TRFs as a function of liver disease severity using the MELD score and assess the role of local and systemic TRFs as predictors of PVT development in cirrhotic patients. METHODS One hundred consecutive patients with liver cirrhosis were included in the study. TRFs, D-dimers, MELD score, portal vein patency and flow velocity were evaluated in all subjects at baseline and every 6 months thereafter. Variables able to predict PVT development within 1 year were identified by means of multiple logistic regression. RESULTS The plasma levels of protein C and antithrombin were lower and the concentration of D-dimers was higher in patients with advanced disease. Plasma levels of antithrombin, protein C and protein S resulted significantly lower in PVT group at univariate analysis, but reduced portal vein flow velocity was the only variable independently associated with PVT development. CONCLUSIONS Lower concentrations of natural coagulation inhibitors are frequently detected in patients with liver cirrhosis. A reduced portal flow velocity seems to be the most important predictive variable for PVT development in patients with cirrhosis.

Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a prevalence case–control study in irritable bowel syndrome

Background:  Studies assessing the prevalence of small intestinal bacterial overgrowth in irritable bowel syndrome gave contrasting results. Differences in criteria to define irritable bowel syndrome patients and methods to assess small intestinal bacterial overgrowth may explain different results. Moreover, no data exist on small intestinal bacterial overgrowth prevalence in a significant population of healthy non‐irritable bowel syndrome subjects.

Safe removal of the radial artery for myocardial revascularization: A doppler study to prevent ischemic complications to the hand

Radial artery harvesting has recently been reintroduced for myocardial revascularization. Harvesting the radial artery may jeopardize the vascularization of the hand; cautious selection of candidates must therefore be pursued. The study involved 188 consecutive patients. We verified the patency of the upper limbs arteries and the adequacy of the ulnar supply by static and dynamic Doppler evaluations. The use of the radial artery was contraindicated in 14 cases (three for stenosis of the subclavian artery and 11 for inadequate collateralization). One hundred patients were operated on with the radial artery used as a graft; the remaining 74 patients had a different conduit placed. The vascularization of the hand was restudied within 10 days in all patients who underwent operation; in 63 patients, it was studied again at 1 year. The early Doppler examination showed significant increase in blood flow velocities in the ulnar artery, with a flow redistribution in the common digital palmar arteries (decreased in the first and increased in the second and the third). The late Doppler examination showed superimposable findings. No local ischemic complications were observed. We conclude that Doppler study is a useful tool in preoperative screening of candidates for radial artery harvesting for myocardial revascularization.

Synergistic Effect of −174 G/C Polymorphism of the Interleukin-6 Gene Promoter and 469 E/K Polymorphism of the Intercellular Adhesion Molecule-1 Gene in Italian Patients With History of Ischemic Stroke

Background and Purpose— Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) are involved in the pathogenetic mechanisms responsible for several ischemic cardiovascular disorders, including cerebral ischemia. IL-6 and ICAM-1 plasma levels and/or function may be genetically influenced. We sought to evaluate distribution and reciprocal interaction of IL-6 G/C gene promoter polymorphism and ICAM-1 E/K gene polymorphism in Italian patients with history of ischemic stroke. Methods— One hundred nineteen patients with history of ischemic stroke and 133 age- and sex-matched controls were studied. IL-6 and ICAM-1 genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis. Results— The GG genotype of −174 IL-6 G/C gene polymorphism was significantly associated with history of ischemic stroke at both univariate (P <0.0001) and multivariate analysis (odds ratio [OR], 8.6;P <0.0001). Additionally, the EE genotype of ICAM-1 E/K gene polymorphism was significantly more common in the group of patients with history of ischemic stroke (P =0.003) and was an independent variable associated with stroke history (OR, 4.0;P =0.002). Interestingly, a further increased risk of stroke was found in subjects who concomitantly carry the IL-6 GG and ICAM-1 EE genotypes (IL-6 GG/ICAM-1 EE double-homozygous subjects) (OR, 10.1;P =0.004). Conclusions— There is a synergistic effect of IL-6 G/C and ICAM-1 E/K gene polymorphisms in patients with stroke history. Reciprocal interactions between genotypes may contribute in determining the risk profile for cardiovascular diseases and may merit further investigation as potential therapeutic targets.

-Rifaximin dose-finding study for the treatment of small intestinal bacterial overgrowth

Background : Few controlled studies assessing choice and duration of antibiotic therapy for small intestinal bacterial overgrowth are available.

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.

Helicobacter pylori Eradication Ameliorates Primary Raynaud's Phenomenon

Raynauds phenomenon is defined by anintermittent vasospasm of the arterioles of the distallimbs. Helicobacter pylori infection has been recentlyassociated with Raynauds phenomenon. The aim of this study was to assess the effects of H. pylorieradication on Raynauds attacks. Forty-six patientsaffected by primary Raynauds phenomenon were evaluated.H. pylori infection was assessed by [13C]urea breath test. Eradication therapy was given toinfected patients for seven days. Discomfort and theduration and frequency of attacks of Raynaudsphenomenon per week were assessed. Thirty-six subjectswere infected with H. pylori; the bacterium waseradicated in 83% of these after therapy. Attacks ofRaynauds phenomenon completely disappeared in 17% ofthe patients with H. pylori eradication. Discomfort and the duration and frequency of attacks ofRaynauds phenomenon were significantly reduced in 72%of the remaining patients. Conversely, attacks ofRaynauds disease did not change significantly during the 12-week follow-up period either in the H.pylori-negative patients or in the infected subjects inwhom the bacterium was not eradicated by therapy. Thestudy shows that H. pylori eradication causes a significant decrease in clinical attacks ofRaynauds disease. The reduction of vasoactivesubstances determined by the eradication of thebacterium may be the pathogenetic mechanism underlyingthe phenomenon.

−174 G/C interleukin-6 gene polymorphism and increased risk of multi-infarct dementia: a case-control study

The aim of this study was to evaluate the association between the -174 G/C polymorphism of interleukin-6 (IL-6) gene promoter and multi-infarct dementia (MID). We studied a group of 122 patients affected by MID and 134 age- and sex-matched controls and evaluated classical risk factors for MID, as well as the distribution of IL-6 alleles and genotypes by polymerase chain reaction and restriction enzyme analysis. The distribution of IL-6 genotypes was 63 GG, 47 GC, 12 CC in patients with MID and 29 GG, 58 GC, 47 CC in control subjects. The GG genotype was significantly more common in the MID group (P<0.0001), while the CC genotype was more common in control patients (P<0.0001). Logistic regression analysis indicated that the presence of GG genotype significantly increases the risk of MID (odds ratio 9.1 [3.1-26.1], P<0.0001). This study indicates a strong association between the -174 G/C polymorphism of the IL-6 gene and MID. Our data support the hypothesis that IL-6 and inflammatory mechanisms are important in the pathophysiology of the vascular changes responsible for cognitive deterioration.

Lack of association between Alzheimer's disease and Gln-Arg 192 Q/R polymorphism of the PON-1 gene in an Italian population.

Alzheimer’s disease (AD) is characterized by deposition of oxidized low-density lipoprotein (LDL) forming the senile plaque and by structural changes and cell death in acetylcholine-producing neurons. Paraoxonase-1 (PON-1) is a secreted protein primarily associated with high-density lipoproteins (HDL) and participates in the prevention of LDL oxidation. PON-1 is also an arylesterase that hydrolyzes paraoxon, an active toxic metabolite of parathion, thus providing protection against organophosphate poisoning and metabolization of environmental neurotoxins that might be responsible for neurodegeneration with aging. Serum levels of PON-1 are genetically determined and strongly influenced by a common polymorphism on the position 192 of the PON-1 gene. The aim of this study was to evaluate whether the polymorphism of the PON-1 gene is associated with AD. We studied 124 Italian subjects affected by probable AD and 135 age- and sex-matched controls. The distribution of PON-1 genotypes was 64 QQ, 46 QR, 14 RR in the AD patients and 57 QQ, 59 QR, 19 RR in the control subjects. No statistically significant difference was found between the two groups in our population (p = 0.130 for homozygous QQ, p = 0.279 for heterozygous QR, and p = 0.502 for homozygous RR). These results suggest that the human Gln-Arg 192 Q/R polymorphism of the PON-1 gene is not associated with AD in an Italian population.

Long saphenous vein stripping reduces local level of reactive oxygen metabolites in patients with varicose disease of the lower limbs.

Long saphenous vein (LSV) stripping is the most common surgical procedure in patients affected by varicose disease of the lower limbs. Reactive oxygen metabolites (ROM) generation plays a crucial role in chronic venous insufficiency (CVI). The aim of this study was to investigate whether ROM generation is increased in patients affected by varicose disease versus healthy controls and whether LSV stripping has a positive effect on the local production of ROM. The local production of ROM was assessed measuring hydroperoxides in the blood collected from the leg of 30 patients consecutively undergoing LSV stripping and 30 controls. In both the patient group and the control group, the test was repeated 30 days later. We found that ROM levels before surgery are higher in varicose vein patients than in controls (p < .0001) and that ROM are significantly reduced 30 days after LSV stripping (p < .0001). At that time point, no significant differences between patients and controls was found. We also found that sex and age do not affect ROM concentration in patients and controls, either before or after surgery. In conclusion, our data indicate that CVI is characterized by significant oxidative stress and that LSV stripping is able to normalize local production of ROM in patients with varicose disease of the lower limbs. We suggest that measurement of ROM might be useful to test the positive effects of LSV stripping in these patients.